immunotherapy

The Society for Immunotherapy of Cancer highlights immunotherapy during Oral, Head and Neck Cancer Awareness Week

Source: www.prweb.com
Author: press release

The Society for Immunotherapy of Cancer (SITC) recognizes Oral, Head and Neck Cancer Awareness Week, April 8-15, 2018, in an effort to highlight targeted immunotherapy to treat patients with these types of cancer.

To educate and guide patients, SITC provides informative and engaging online education dedicated to cancer immunotherapy through SITC Cancer Immunotherapy connectED. Two head and neck cancer-specific resources are available on SITC connectED:

Beyond Chemotherapy for Treatment of Head and Neck Cancer: Developed for patients with head and neck cancers and their care partners, the goal of this online class is to learn about treatment options for the newly diagnosed, treatment after chemotherapy, and questions to ask the patient’s healthcare team.

Understanding Cancer Immunotherapy Patient Resource Guide: This guide provides current, medically accurate information on cancer (including head and neck cancers) – intended for patients and caregivers to outline available cancer immunotherapy options, the role of the immune system in this type of cancer treatment and what to expect while undergoing treatment. (free registration required)

Aiming to make cancer immunotherapy a standard of care for cancer patients everywhere, these SITC connectED resources educate and guide patients on immunotherapy treatment options for head and neck cancer. For more information, visit the SITC website at sitcancer.org.

About SITC
Established in 1984, the Society for Immunotherapy of Cancer (SITC) is a nonprofit organization of medical professionals dedicated to improving cancer patient outcomes by advancing the development, science and application of cancer immunotherapy and tumor immunology. SITC is comprised of influential basic and translational scientists, practitioners, health care professionals, government leaders and industry professionals around the globe. Through educational initiatives that foster scientific exchange and collaboration among leaders in the field, SITC aims to one day make the word “cure” a reality for cancer patients everywhere. Learn more about SITC, our educational offerings and other resources at sitcancer.org and follow us on Twitter, LinkedIn, Facebook and YouTube.

April, 2018|Oral Cancer News|

Evolving role of surgery in multidisciplinary care for head and neck cancer

Source: www.onclive.com
Author: Danielle Bucco

Even with the advent of systemic therapeutic advancements to the armamentarium of head and neck cancer, surgery and novel techniques continue to rapidly evolve to effectively treat patients and leave less opportunity for adverse events (AEs).

Additionally, the role of the surgeon has changed to be a more integrative role in patient care.

“We are more precise and more integrated with other therapeutic modalities,” said Joseph A. Califano, MD. “Together, we work as a team and that is the best way that patients can receive their optimal outcomes. We do not just want to cure their cancer but to get back to function and wellness.”

In an interview during the 2017 OncLive State of the Science SummitTM on Head and Neck Squamous Cell Carcinoma, Califano, a professor of surgery at the University of California, San Diego, discussed how surgery factors into modern multidisciplinary care for patients with head and neck cancer.

OncLive: Please provide an overview of your presentation on surgery for patients with head and neck cancer.
Califano: I discussed the fact that the surgery that we do now for head and neck cancers is very different from what used to be done 15 to 20 years ago. Our ability to do effective surgery is good, but now we can do it in a way that leaves patients with excellent function and cosmetic results.

When you see someone walking down the street who has had major head and neck surgery, you wouldn’t know it because we are doing new techniques that are going through natural orifices to do major significant surgeries.

Can you discuss robotic surgery in this space?
Robotic surgery is part of what we do as head and neck surgeons. It is effective in terms of taking care of tumors—particularly in the throat, the tonsils, the back of the tongue, and perhaps even in the nasopharynx. Ordinarily, we cannot get to them unless we have robotic instrumentation. The beauty of robotic surgery in this setting is that we can have patients with excellent function, good swallowing, good voice, and rapid recovery from a significant procedure that was not available 10 years ago.

How do you believe surgeons fit into multidisciplinary care in head
and neck cancer?
Multidisciplinary care is one of the most important things that we practice when we take care of patients with head and neck cancer. It is not just medical professionals who do chemotherapy or radiation surgery; it is a whole host of other people, such as speech pathologists, dentists, dieticians, social workers, nurses, occupational therapists, and physical therapists.

The reason this is so important is that the effects of our therapy combined are good in terms of curing cancers. The AEs need to be treated. We need to get people back to not just curative cancer, but functioning and happy, as well.

What is your message to community oncologists who do not understand the importance of surgery when systemic therapies are available?
Together as a team, we can do much more effective therapy and leave people with much better functions than we could in isolation. The second message is that surgery has rapidly evolved in the past 5 to 10 years. If you are a community oncologist or a community radiation oncologist, you do not realize that we can treat diseases that 10 years ago were treated with radiotherapy alone. We can very effectively treat with surgery alone or in combination with radiation therapy to reduce the AEs. Those AEs are what our patients are going to feel 10 or 15 years down the road.

For example, the risk of stroke after radiotherapy long term is as high as 6% at 12 years. If we can treat people effectively with surgery alone, then we can eliminate that risk of stroke and eliminate some of the long-term effects of other therapies.

What are some big concerns in head and neck cancer and what would you like to see addressed in the next 5 to 10 years?
Some of the newer targeted therapy and immunotherapy approaches are going to blend in well with surgery; it will be one way we can tell whether someone responds to a systemic agent. For example, if a patient receives immunotherapy alone and has a complete response, we can do a minimally invasive surgery to not only make sure that we clear the disease but even to document that there is no disease and spare the patient additional therapy.

The second thing I would say is that we are going to have a host of imaging technologies available. They are just starting to become clinically applicable. We are going to know exactly where the tumor is so that when we do surgery, we can make sure that we get all the cancer [out] most of the time and reduce the need for additional therapy, such as debilitating combination therapy. We can choose who is good for surgery, who is not, and who is better treated with other therapeutic approaches, such as radiation, chemotherapy, immunotherapy, and targeted therapy.

How is surgery an integrated part of the team?
Historically, we are unlike a lot of other surgeries. We follow our patients throughout the rest of their lifetimes and we are an integrated part of the care team. There are other things we can do as surgeons, for example. We can move salivary glands out of the way of radiation for patients with good saliva function to swallow better and have a better quality of life.

We do not think of ourselves as an isolated [group] to take out the cancer, but we are also there to reconstruct, rehabilitate, and help people get on their way to being well.

The head and neck is all about who we are, how we interact socially, and how we feel about ourselves. Social things that we do with other people are eating, talking, and communicating. There are many who now have these functions after head and neck cancer.

December, 2017|Oral Cancer News|

What’s next after creating a cancer-prevention vaccine?

Source: www.scientificamerican.com
Author: Dina Fine Maron

A winner of this year’s Lasker Awards talks about his work with HPV

Imagine a vaccine that protects against more than a half-dozen types of cancer—and has a decade of data and experience behind it.

We have one. It’s the human papillomavirus (HPV) vaccine, and it was approved for the U.S. market back in June 2006. It can prevent almost all cervical cancers and protect against cancers of the mouth, throat and anus. It also combats the sexually transmitted genital warts that some forms of the virus can cause.

On Wednesday, two researchers who completed fundamental work on these vaccines received one of this year’s prestigious Lasker Awards, a group of medical prizes sometimes called the “American Nobels.” Douglas Lowy and John Schiller, whose research provided the basis for the HPV vaccine, were selected alongside a researcher who separately unraveled key aspects of metabolic control of cell growth. Planned Parenthood was also given an award, for its public service. Lowy and Schiller, who both work at the U.S. National Cancer Institute (NCI), received the Lasker for their research on animal and human papillomaviruses—work that enabled the development of a vaccine against HPV-16 type, a form of the virus that fuels many HPV malignancies. The duo’s experiments proved that the vaccine is effective in animals, and they also conducted the first clinical trial of an HPV-16 vaccine in humans. That gave pharmaceutical companies the evidence they needed to invest in their own vaccines designed to protect against multiple kinds of HPV, and ultimately led to the versions administered around the world today.

Yet HPV shots have had a difficult run. Despite overwhelming evidence of their safety and effectiveness, in some developed countries—including the U.S.—HPV inoculations face opposition from individuals and groups that fear the shots are still too new and unproved to use on their children. The HPV vaccine also faces another hurdle beyond other routine pediatric shots: the virus is transmitted via sexual contact—which some parents and communities believe teens should not or will not have, and thus that the shots should not be mandatory. (The U.S. Centers for Disease Control and Prevention [CDC] currently recommends administering two doses of the vaccines to children 11 to 12 years old, administered at least six months apart.)

Scientific American spoke with Schiller, a virologist, about his and Lowy’s award-winning HPV research, their future plans and how to combat anti-vaccine attitudes.

[An edited transcript of the interview follows.]

What’s the biggest hurdle to getting more coverage with the HPV vaccine?
The biggest problem is actually not in the West or most developed countries; it is in the lower- and middle-income countries because of availability there and vaccine prices that limit availability. In those settings vaccine acceptance is actually very high. But those settings present the biggest problem, since some 85 percent of cervical cancers occur in low-resource settings. In the more developed countries there are many different factors involved [in vaccine hesitancy], and they differ by country. In the U.S. it is more about fear of vaccines in general. And there are some issues with HPV vaccines specifically related to this being about a sexually transmitted disease.

So far, more than 270 million doses of HPV vaccines have been distributed worldwide. But in the United States, by 2015 only 28 percent of teen males and 42 percent of teen girls had received the full course of three shots then recommended by the CDC. How can the science community help combat HPV vaccine hesitancy?
There are quite a few studies that show one of the biggest issues is that the vaccine is not being promoted sufficiently by pediatricians and general practitioners. If you look at other vaccines like for meningitis and hepatitis B—which are also administered to adolescents and could be given in the same visit as HPV—they are given at greater rates than HPV. So, there is some disconnect in communication between pediatricians and parents there. Part of the problem here is that the HPV vaccine is a prophylactic vaccine to prevent a disease—cervical cancer—that those providers never see. Obstetrician-gynecologists see it, but pediatricians don’t, which is the opposite of most other childhood or pediatric vaccines. Right now it’s being singled out as something special instead of treated as a routine childhood or adolescent vaccine. But we’ve had this vaccine for 10 years now and it’s not the new kid on the block anymore.

Mounting evidence suggests that among people who feel vaccines are unsafe, any new data showing that they arereally safe does not move the needle to convince them. So, what can be done?
My feeling is that there is a certain percentage of people who, no matter what facts you present to them, they are just not going to be convinced. Quite frankly it doesn’t pay to spend a lot of resources trying to convince that relatively small fraction. What we need to focus on is a much larger fraction of the population who aren’t having their kids vaccinated for reasons like convenience—like it’s a hassle—or they just need a bit more information to make them comfortable. People against all vaccines, those people would not be convinced to get an HPV vaccine so it’s not worth spending a lot of resources on them. I think one of the things that would increase HPV vaccine coverage would be allowing people to get them at their local CVS. I’m not an expert on this, but I have a daughter who as a teen spent much more time at the local CVS than at her local Kaiser clinic. Different states have different laws about which vaccines can and can’t be delivered at pharmacies—but if someone could go get an HPV vaccine at the same place they get their flu vaccine, presumably it would lead to an uptick.

I see you studied molecular biology as an undergrad at the University of Wisconsin–Madison. Did you always want to work on vaccines?
No, absolutely not. When I first started out I was an academic purist and thought you should study knowledge for its own sake. I was fascinated by molecular biology. When I first heard about the way metabolism works in bacteria, plants and humans, that just wowed me because that was a common feature of all life. I just wanted to study that. I thought people who did translational work were sort of selling out to the man—this was in the 1970s. I didn’t get interested in vaccines until much later. Now, I’m very fascinated with translational research.

So, what changed?
It was a very gradual thing. To this day we still do basic research, and it’s still intrinsically valuable to do basic research because you don’t know when it will lead to a transformational breakthrough.

What led you to work on HPV?
When I had just joined the field, suddenly there was this discovery that made papilloma viruses important for human health as opposed to just an understanding of how cells become cancerous. I had joined Doug Lowy’s lab at the National Cancer Institute as a postdoc back in 1983, and the second lecture I went to there was by Harald zur Hausen—who later won the Nobel Prize—and his lecture was saying “eureka! We found a virus that seems to cause 50 percent of cervical cancers”—and that virus turned out to be a human papilloma virus strain, HPV-16. So basically we went from looking at a model about how a normal cell transforms to become carcinogenic to something probably involved in causing human cancer. It was somewhat serendipitous.

What are you working on now?
One thing we are doing at the NCI, and cosponsored by the Bill & Melinda Gates Foundation, is testing if one dose of HPV vaccine is enough to provide long-term protection. It would be transformative, especially in the developing country setting, if you could just have one dose at a younger age. This new trial is going to be done in Costa Rica in collaboration with the Costa Rican government. That’s the site where we had done a prior pilot trial that suggested one dose may be enough.

We are also looking into cancer immunotherapy work. It turns out that these virus-like particles that we work with for the HPV vaccine—these are typically the outer shell of a virus, like from the HPV-16 strain or other animal, or human papilloma virus particles—have a unique ability to infect tumor cells and bind to them specifically. So we are using that knowledge to develop cancer therapies that are broad-spectrum. It turns out these cancers, like melanoma, do bind these particles, specifically.

One other thing we are doing is trying to develop vaccines that would treat herpes simplex infections and HPV infections in the female genital tract. Again, this would take advantage of these virus-like particles’ structures.

Last year I interviewed Michael Sofia, who won a Lasker Award for his hepatitis C vaccine work. The name of that vaccine, sofosbuvir—brand name Sovaldi—is a nod to his last name. But the National Institutes of Health (NIH) do a lot of early-stage research, and then it’s passed off to private companies that develop it further. Your name isn’t part of the HPV vaccines Gardasil or Cervarix, for example. Is it frustrating doing a lot of that behind-the-scenes work?
It’s funny because I would never have thought of that. It would have never entered my mind to name a vaccine after ourselves. We are so used to doing this translational work. My job is to move a project along so it’s interesting enough for a company to invest hundreds of millions of dollars for the benefit of large numbers of people. NIH doesn’t have the money to do phase III trials for lots of drugs, and even if they did it wouldn’t lead to all the drugs we need—because NIH wouldn’t have the money to develop them. This translational and basic research is what NIH does best. That work is way too fraught with failure for companies to do it all. It has to be done in the public sector, and then when things look more promising companies can take it over.

What advice would you offer someone considering becoming a scientist now?

It’s got to be a passion because being a scientist—especially early in your career—is more a lifestyle than occupation. You have to really want to do it, because there is a lot of uncertainty—especially about running your own lab and getting funding. Success and failure can be on a knife’s edge sometimes. The other thing is that you need to be strategic about thinking of what you want to go into, and that’s hard for young people because they don’t have the perspective: There are some fields just opening up ripe for discoveries. And there are some areas that are very mature, that we have been working on for a long time, where there are a lot of scientists working already—so the chances of making a big impact are lower. From my own life, this is like when we started with human papilloma viruses. When I went into this field, we had just been given the tools to study them and so it seemed like a great opportunity to get involved. In some ways it’s best if you can pick an emerging field with new tools to answer big questions. But you have to pick something you are really interested in and go with it.

The other thing I’d say is read a lot. Now with PubMed and access to all these journals there is no excuse for not knowing the background in something that basically has already been done. Young people tend to want to get out and do experiments, but a few days searching PubMed may save someone years of work trying to reinvent the wheel.

Right now, what would you say is the biggest challenge—or one of the biggest challenges—that needs to be solved?
That’s a really tough one. I think as scientists we are all sort of locked into the things we study. I could say cancer, obviously. But Alzheimer’s is something we obviously need to solve. HIV infection. All these different things. One of the things that really needs to be solved in terms of the whole scientific enterprise now is stable funding. Right now we are in a situation where there are too many good scientists—especially young scientists—competing for a limited pot of money. So you lose some good people because there’s not enough money to go around. Also, people are forced to do relatively mundane things that are really a methodological extension of something they’ve done before instead of something truly transformative that would have a large chance of failure. Grant reviewers are looking at something likely to succeed and move the field incrementally, or something transformative that may have a high chance of failure, and have to make those decisions. This is an issue across the sciences. The obvious solution would be to have more funding, but then that raises the question about how to do that. And I’m not a politician.

What, if anything, does this Lasker Award do for your work?
Quite honestly, probably nothing, because one of the nice things about being part of intramural research [at NIH] is that I have stable funding. I’ve had six people in my lab for the last 25 years, so this won’t lead to more grants or me doubling the size of my lab, or anything like that. I’m happy with my moderate-sized lab and collaborations with a lot of great people. That’s why I’m here. Every four years we have a site visit, which is a retrospective review of “what have you done for us lately,” and if it’s reasonable I will continue to get funding. So the award won’t affect my research career much at all.

Right now, some in the scientific community fear amid this political climate that facts matter less than they once did and thus science matters less. What’s your take on that?
Obviously, my perspective is science matters a lot. I really can’t comment on what’s happening in the country overall—and whether this is something that is pervasive where science is really held in less esteem, or it’s that there is a vocal minority being heard a lot now. I would hope it’s the latter.

September, 2017|Oral Cancer News|

Health Beat: Hunting head and neck cancer cells

Source: www.wfmz.com
Author: Melanie Falcon

Leonard Monteith led a healthy lifestyle. That’s why sudden problems with his mouth caught his attention.

“I noticed that when I would stick my tongue out, it would deviate to one side, and I thought that’s not right,” said Monteith, 66.

Doctors found an inch-wide tumor at the base of Monteith’s tongue. He was diagnosed with HPV positive cancer.

“The traditional treatment for head and neck cancer is really toxic and exhaustive and leads to side-effects that are very significant,” said Dr. Nabil Saba, a medical oncologist at Emory University Winship Cancer Institute in Atlanta.

After treatment, Monteith’s cancer went away for six months, but then it came back in his lungs.

Saba is a nationally-known expert in the treatment of head and neck cancers. He thought Monteith would be a good candidate for a new therapy.

“Immunotherapy is really, I think, a complete game changer,” said Saba.

Saba said two separate immunotherapy drugs are showing real promise. A drug called Nivolumab blocks the cancer receptors, allowing the body’s immune system to fight the cancer. Another drug, Pembrolizumab, also works in a similar way.

Because the trials are ongoing, Saba can’t say which specific drug Monteith was on.

“He had very good response to the treatment, to the point where we could not see any more lung lesions on the scan,” Saba said.

Monteith has been improving for three years, but he knows his condition could change without warning.

“I just live my life as I think I would have anyway,” said Monteith.

Doctors say the survival rates for patients who continued on Nivolumab were twice of those who did not take the immunotherapy drug. Twenty percent of the patients on the drug had their tumors shrink.

Research Summary: Hunting head and neck cancer cells (pdf format)

Magnolia man joins exclusive trial in battle against cancer

Source: www.cantonrep.com
Author: Denise Sautters

Rich Bartlett is looking forward to getting back to his hobbies — woodworking and nature watching — and enjoying a good steak and potato dinner. Until then, though, he is in a fight for his life, one he plans to win.

Bartlett is a cancer patient and the first participant in a clinical trial at University Hospitals Seidman Cancer Center in Cleveland to test the safety of an immunotherapy drug — Pembrolizumab — when added to a regimen of surgery, chemotherapy and radiation therapy.

Back to the beginning
Bartlett went to the dentist in October for a checkup.

“He had a sore in his mouth he thought was an abscess,” explained his wife, Nancy Bartlett, who pointed out that, because radiation and chemo treatments cause the inside of the mouth to burn and blister, it is hard for Bartlett to talk.

“When the dentist looked at his sore, he sent Richard to a specialist in Canton, and in early November, he had a biopsy done. It came back positive for cancer.”

From there, he was referred to Dr. Pierre Lavertu, director of head and neck surgery and oncology at University Hospitals, and Dr. Chad Zender from the otolaryngology department, who did Bartlett’s surgery.

“They let us know it was serious,” said Nancy. “It had gone into the bone and the roof of the mouth, but they were not sure if it had gone into the lymph nodes. By the time we got through that appointment, it was the first part of December and (they) scheduled him for surgery on Dec. 22.”

The cancer tripled in size by then and the surgery lasted 10 hours. Doctors had to remove the tumor, all of the lymph nodes and parts of the jaw and the roof of Bartlett’s mouth.

“They harvested skin from his hand to rebuild the inside of his mouth, and took the veins and arteries and reattached everything through his (right) cheek,” she said. “He could not even have water until February because of the patch. He uses a feeding tube to eat now.”

The tube is temporary until Bartlett heals.

Clinical trial
Just before he started chemo and radiation therapies, the hospital called him about the clinical trial.

The trial is the first to use quadra-modality therapy — or four different types of therapy — against the cancer, according to Dr. Min Yao, the principal investigator.

Yao said Bartlett has squamous cell carcinoma of the oral cavity, with only a 50 percent chance of survival.

“Patients have surgery, then followed by six weeks of radiation and chemotherapy and immunotherapy,” Yao said in an email interview. “That is followed by six more months of immunotherapy, one dose every three weeks.”

Bartlett currently is in the radiation, chemotherapy and immunotherapy part of the study.

“It is too early to tell how he is responding,” said Yao. “His tumor has been resected. After the treatment, we will see them periodically with scans. Cancer often recurs in the first two years after treatment.”

Pembrolizumab originally was developed to activate the body’s immune system in the fight against melanoma. Former president Jimmy Carter was treated with the drug for his brain metastases from melanoma in 2015.

A truck driver by trade, Bartlett will undergo daily fluoride treatments for the rest of his life to protect his teeth.

“We did not realize until we got to Cleveland just how bad this was,” said Nancy. “When you have oral cancer, and they are getting ready to do radiation and chemo, you have to go have your teeth cleaned and examined and get anything done that needs to be done because radiation tends to compromise your blood flow in your mouth. That was a step we didn’t know.”

Although he was shocked to hear the outcome of that sore in his mouth, Bartlett is grateful to be a part of the trial.

“Who wouldn’t feel good about something like this? I mean, you got something that was used on Jimmy Carter, who is recovered and is now making public appearances again,” said Bartlett, who is looking forward to June when hopefully he can start eating again and enjoying his hobbies.

“I am very hopeful about this. The whole thing has been a trial. I have a dentist in Cleveland who said I was going to be in the fight of my life, and I am. I am in a huge fight. The chemotherapy is what has knocked me down the most, but I am very positive about the outcome of this.”

March, 2017|Oral Cancer News|

Immunotherapies Form New Frontier in Treating Head and Neck Cancers

Source: OncLive.com

Date: January 2nd, 2017

In August 2016, the FDA approved pembrolizumab (Keytruda) for patients with platinum-refractory squamous cell carcinoma of the head and neck (SCCHN).1 Not only was it the first immunotherapy approved for head and neck cancer (HNC), but it marked the first new drug approval for HNC in the United States in 20 years.

“Now we have an agent that really changes the paradigm—a new class of treatment—and we are seeing amazing benefit in some patients,” said Tanguy Seiwert, MD, during an OncLive Peer Exchange® panel held during the 2016 European Society for Medical Oncology (ESMO) Annual Meeting.

Less than a month later, the menu of immunotherapy options expanded as the FDA approved nivolumab (Opdivo) for the treatment of patients with recurrent or metastatic SCCHN with disease progression on or after a platinum-based therapy.

During the Peer Exchange, the panelists provided an overview of the immunotherapy terrain in HNC, a discussion that was filled with considerable hope and excitement. “When we try immunotherapies in the second-line setting, we see objective responses—sometimes deep, clinically meaningful, extremely durable responses—and we’re beginning to think that maybe, on some occasions, we may be able to cure patients with relapsed metastatic head and neck cancer,” said Kevin Harrington, MD, PhD. This is especially remarkable since such patients have generally had a survival of ≤1 year.

The panelists concurred that the care of patients with HNC will evolve significantly over the next 5 to 10 years, as the tip of the immunotherapy iceberg is just starting to be scratched. During the Peer Exchange, they provided a rationale for using immunotherapies in HNC, including human papillomavirus (HPV)-positive and HPV-negative disease; outlined key immunotherapy studies; and offered their thoughts on the future of immunotherapies in HNC, including use of biomarkers to guide therapy and the opportunity to improve response by using combination treatments.

“Next-generation sequencing efforts are beginning to shed light on the hidden complexities of these tumors, leading to the identification of multiple molecular subtypes,” said Ezra Cohen, MD, who served as moderator for the session. “As key differences between tumors, with and without HPV infection, are beginning to emerge, the challenge is to find ways to use this information to personalize treatment for individual patients.”

Rationale for Immunotherapy in HNC

In patients with locally advanced HNC, HPV status has generally determined outcomes, with HPV-positive patients having a good prognosis and higher likelihood of cure, and HPV-negative patients having a poorer prognosis and a lower likelihood of cure.

However, outcomes with conventional therapy in recurrent metastatic disease have been poor across the board, especially in the setting of platinum- refractory disease, indicating a tremendous unmet need. Before pembrolizumab was approved in this setting, the recommendation was to use a taxane, such as methotrexate or cetuximab (Erbitux), as a single agent, but the outcomes have been unsatisfactory. In contrast, immunotherapy studies have shown promising results in these patients, with HPV-negative patients also benefiting.

“The rationale for [using immunotherapies] for HPV-positive tumors may be the virus, as well as mutations, and for HPV-negative tumors, it’s likely the mutation load,” said Seiwert. He explained that HPV-negative tumors are often smoking-associated tumors and, therefore, have high mutation loads, a factor that has been associated with good response to immunotherapy, whereas HPV-positive tumors resemble melanoma, with significant inflammation, another factor associated with good response.

Although efficacy was found to be the same for HPV-positive and HPV-negative tumors in KEYNOTE-012, which was the study that led to pembrolizumab’s approval for HNC, some CheckMate-141 subanalyses suggest there might be slightly more activity in HPV-positive patients, noted Seiwert.

Despite such findings, he said, “HPV status should not actually dissuade us one way or the other from using immunotherapy—it’s clearly active in both HPV-negative and HPV-positive tumors.” And, as Harrington pointed out earlier in the discussion, since nothing else works well in the second-line setting, “why not try it?”

Key Pembrolizumab Studies

The panelists proceeded to provide an overview of several instrumental pembrolizumab studies, including the KEYNOTE-012 expansion study and KEYNOTE-055 studies, and of the phase III CheckMate-141 study, which paved the way for nivolumab’s approval.2-4 They also discussed a subanalysis of CheckMate-141 presented at ESMO that demonstrated good patient-reported outcomes following nivolumab therapy, lending further support to its use in SCCHN.5

KEYNOTE-012 Expansion Study

The phase Ib KEYNOTE-012 expansion study administered 200 mg of pembrolizumab intravenously once every 3 weeks to 132 patients with recurrent or metastatic SCCHN, irrespective of their programmed death-ligand 1 (PD-L1) or HPV status.2 Primary endpoints included overall response rate (ORR), and safety and secondary endpoints included progression-free survival (PFS), overall survival (OS), and PD-L1 expression’s impact on response.

Pembrolizumab was well tolerated, and yielded a clinically meaningful ORR with evidence of durable responses; median duration of response was not reached. The ORR was 18% by central imaging vendor review and 20% by investigator analysis. A statistically significant increase in ORR was observed for PD-L1–positive versus PD- L1–negative patients (22% vs 4%, respectively; P = .021).

At 6 months, PFS and OS rates were 23% and 59%, respectively. “And we have patients living far beyond what we usually expect for metastatic disease…we now have patients who have completed 2 years of treatment in a setting with a median life expectancy of about 6 months,” revealed Seiwert, who is involved with the study.

Pembrolizumab was also well tolerated. Grade ≥3 events occurred in 9% of patients. “[This is] within the range of toxicities that we have seen in other studies,” said Viktor Grünwald, MD. “Because we’re approaching a very sick and morbid patient population, we might expect different toxicity outcomes, so I think it’s very reassuring that we’re seeing the same amount of toxicity as in other studies,” he explained.

While checkpoint inhibitors are generally well tolerated and have favorable toxicity profiles, the panelists warned that severe side effects can occur and careful patient monitoring is required. A key concern they discussed is pneumonitis.

“Although it only occurs in about 1% to 2% of patients, you must screen for it because it’s life threatening,” said Seiwert. “If somebody says, ‘I am short of breath’ or ‘I have a little bit of a cough,’ I scan them right away to look for it,” he said, explaining that immediate treatment with high-dose steroids is warranted.

KEYNOTE-055 Preliminary Results

KEYNOTE-055 enrolled 172 patients with recurrent or metastatic SCCHN to receive pembrolizumab 200 mg every 3 weeks after progression on platinum plus cetuximab. The preliminary analysis, which reported on 92 evaluable patients, was initially presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.3 Primary endpoints include ORR and safety.

As with KEYNOTE-012, pembrolizumab was found to be well tolerated and to have significant antitumor activity, with 17% to 18% response rates. Evaluation of the full study cohort will include analyses of HPV status and response by anatomic site. “I think that’s the story we’re seeing for pembrolizumab in head and neck cancer—patients are already being treated in single-arm clinical studies, which is somewhat unusual, but reflects the speed of knowledge that we’re gaining that is leading to approvals,” said Grünwald.

Nivolumab also had a lower incidence of treatment-related adverse events (TRAEs) than IC. Any grade TRAEs occurred in 59.3% and 77.5% of patients on nivolumab or IC, respectively. Grade 3/4 TRAEs occurred in 13.6% and 35.1% of patients, respectively, indicating the treatment is well tolerated, which also translated to improvements in quality of life in the patient-reported outcomes study.5

“A very detailed analysis of patient-reported outcomes using 3 well-validated questionnaires showed nivolumab was able to maintain good patient-re- ported outcomes in terms of their quality of life, their functioning, and their symptom scores, whereas IC showed serious detriment in those scores,” said Harrington.

In the study,5 patients treated with nivolumab had delayed worsening of functioning and symptoms compared with IC at approximately 4 months of follow-up, with patients receiving nivolumab reporting longer maintenance of function and less pain, fatigue, and dyspnea on treatment, as compared with those receiving IC.

“So not only do we have clear evidence that these drugs can work in terms of improving survival and delivering meaningful responses, but they do so with fewer episodes of treatment-related toxicity and disease-associated morbidity,” said Harrington.

Future of Immunotherapy in HNC

The panelists noted that use of biomarkers and combination therapies are key areas of future development for HNC. Both areas are already being examined in clinical trials and have relevance across the vast HNC spectrum, from those with minimal disease to those with previously treated advanced disease, potentially offering a curative pathway to more patients.

“It’s fantastic to have drugs that work in second-line relapsed metastatic or first-line metastatic setting, but what I want and what patients want is to be cured at the time they first present with their disease so they never have treatment in relapsed metastatic setting,” said Harrington.

Biomarkers

Although biomarkers such as PD-L1 expression are already being used and can help identify patients who are more likely to respond, high PD-L1 expression does not guarantee response, nor does no or low PD-L1 expression ensure lack of response or lack of durable response.

Subsequently, use of pembrolizumab and nivolumab is without use of this biomarker for patient selection. “While [a PD-L1 assay] can help inform patients of their likelihood to respond, it is not an assay that can select patients,” said Seiwert, who is working to identify novel biomarkers.

“I’ve been involved in looking at a novel biomarker called interferon gamma signature, which can be assayed quite easily with a rapid turn-around, and seems to perform somewhat better than PD-L1 expression,” said Seiwert. “It seems to have a high negative predictive value, and it may eventually allow us to exclude some patients who have no chance of having benefit, but it needs further validation.” He said that other biomarkers are also under investigation, including mutational load, immunogenic mutations, and dynamic biomarkers, but all are still experimental.

“What we really need is a biomarker that would predict progressive disease,” said Grünwald. “To me, that would be much more usable than an assay that just allows us to say to patients ‘your chance of response is 30%.’ I see biomarkers as having the potential to guide development of treatment algorithms,” he said.

Combinations

Currently, PD-L1–targeted agents have seen the greatest development, and studies are starting to suggest that response with these agents can be enhanced when they are combined with other treatments, including chemotherapy, CTLA-4 blockade, and radiotherapy. “About 70% of HNCs have some level of PD-L1 expression—some level of inflammation—but we only see responses in 15% to 18% of patients, so the pool of patients who might benefit from combinations is huge,” said Seiwert.

He noted that the melanoma and lung cancer settings have already shown combining PD-1 inhibitors with chemotherapy or a second checkpoint inhibitor to be particularly promising in the front line, and he suspects one or both combinations will eventually receive approval in these settings and warrant serious investigation for patients with SCCHN.

“Some of our patients do not benefit from a checkpoint inhibitor, and we can’t identify these patients in advance, but giving them chemotherapy might buy us time,” he said. “It’s almost like a pharmacodynamic effect, where we have more time for the immunotherapy to work, and maybe, also make the immune system stronger and expose antigens.”

In the locally advanced setting, animal studies have shown promise combining chemoradiotherapy with immunotherapy, but results of a small study presented at ESMO revealed some dosing challenges in humans.6

In the study, 18 patients with various forms of intermediate- or high-risk SCCHN received ipilimumab, an anti–CTLA-4 antibody, in addition to standard intensity-modulated radiotherapy with cetuximab. Dermatologic immune-related adverse events limited dosing. “There are some safety hints that it may not be a piece of cake getting through radiotherapy, and maybe cetuximab might not be the optimal part now, but I think there is still a lot of promise combining radiochemotherapy with immunotherapy,” said Grünwald. “It could be a future way in how we successfully treat early forms of localized SCCHN.”

Combining checkpoint inhibition with radiation is another intriguing combination, and one that has the potential to act like an in situ vaccination that can lead to abscopal responses (ie, responses at distant sites), noted Harrington, something he has, thus far, only observed rarely with radiation.

“The idea behind combining checkpoint inhibition and radiation is that we could use the confluence of the two different mechanisms to make abscopal responses more predictable and more effective at a distant site, while engendering an immunologically relevant response that allows us to treat macroscopic metastatic disease while also getting rid of micrometastatic disease that could lead to metastatic failure,” he said.

Although immunotherapy combinations are showing promise in SCCHN and other cancers, the panelists warned that they should only be attempted as part of clinical trials. “There are still a lot of question marks about combinations, so they must be done as part of a clinical trial,” said Seiwert. Not only are toxicities and immunosuppressive effects best managed in clinical trials, but trials are essential in advancing these therapies and identifying the next breakthroughs in the field, he said.

 

“This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.”

January, 2017|Oral Cancer News|

Blood-borne HPV antibodies indicate head, neck cancer prognosis

Source: medicalxpress.com
Author: provided by Brown University

People with head and neck cancers with evidence of human papillomavirus (HPV) infection generally have a better prognosis than people without evidence of infection. A new study in JAMA Oncology suggests that to produce a strong, reliable prognostic signal, all that’s needed is a blood serum test for two specific HPV antibodies, rather than lab work on a biopsy. Further, the researchers said, the study shows that this blood-based biomarker is predictive of outcome for all types of head and neck cancer.

bloodbornehp

The human papillomavirus causes not only cervical cancer but also cancers of the head and neck. Credit: National Cancer Institute

“What this adds is that it helps us know how best to measure clinically the HPV contribution to this disease,” said study senior author Karl Kelsey, a professor of epidemiology and of pathology and laboratory medicine at Brown University. Kelsey collaborated with lead author Heather Nelson of the University of Minnesota Masonic Cancer Center in making the findings.

Moreover, Nelson, Kelsey and their colleagues wrote, referring to the common HPV16 strain of the virus: “These data are among the first to demonstrate a convincing relationship between HPV16 and improved patient survival for tumors of the larynx and oral cavity.”

Appraising antibodies
The study examined blood serum samples and five-year survival rates among more than 1,000 Boston-area head and neck cancer patients diagnosed between 1999 and 2011. Overall, those who tested positive for antibodies to the oncogenic HPV proteins E6 or E7 were less likely to die during the five year follow-up period after diagnosis compared to those who tested negative for the antibodies. Based on the analysis, the researchers estimated that those with evidence of an immune response to HPV were 25% less likely to die during the course of follow-up compared to those with no immune response to HPV.

The study’s purpose was to determine whether the antibodies provide a reliable indication of prognosis. In ongoing trials, doctors are testing whether patients with HPV-associated cancers can be treated less aggressively—and hopefully with fewer negative side effects—than people with non-HPV-associated cancers, Kelsey said. If trials prove successful, then it will be particularly important to determine whether cancers are HPV-associated.

“The assessment of a patient’s HPV status likely will affect treatment,” he said. “That’s why there’s real interest in getting it right; for instance, how do you test?”

Better prognosis across the board
Prior studies have focused primarily on the role of HPV in the oropharynx—the area of the throat right behind the mouth. An important contribution of the current study, Nelson said, is demonstration that an immune response to HPV is important for all forms of head and neck cancer, although the benefit does show some variance based on the exact cancer location. Those patients with an HPV immune response with tumors located in the oropharynx and larynx had a similar risk of dying during the follow-up period, though the reduced risk was slightly attenuated for those patients with tumors located in the oral cavity.

The results didn’t depend significantly on whether people had high or low levels of the antibodies, so long as they had some, the researchers found, though testing positive for both E6 and E7 was better than for just one.

The reduced chance of dying by five years carried through for people who tested positive for the antibodies even if they consumed tobacco and alcohol. But the worst prognoses in the study were among smokers whose cancers could not be traced to HPV.

In all, the findings controlled for the statistical influences not only of tobacco and alcohol exposure, but also of age, race, gender, education and how far advanced the cancer was.

Relates to broader advances
Kelsey said the findings could help bring head and neck cancer treatment closer into line with two emerging practices of fighting the disease: personalized medicine and immunotherapy.

“To me, personalized medicine really reflects using all the information you can glean about an individual tumor to treat it appropriately,” Kelsey said. “Here HPV is an example of a causal factor that delineates the mechanism of the tumor suppressor genes that drive the tumor and that gives you insight into the differences in the tumor.”

Meanwhile, the study might help shed light on why immunotherapy—in which the body’s immune system is marshaled to attack cancer—appears to help for some head and neck cancers, Kelsey said. It may not be coincidence, for instance, that the prognosis is better among people whose cancers are associated with a virus that promotes a robust immune response, in the form of antibodies, than among people without a viral cause for their cancer.

If HPV-related cancers can indeed be treated differently, Kelsey said, then serum-based testing to determine the role of the virus could soon be available, too.

December, 2016|Oral Cancer News|

I get by with help from my friends: Maintaining immune cells in head and neck cancer

Source: www.eurekalert.org
Author: Medical University of South Carolina

In an article published September 22, 2016 in Frontiers in Immunology, researchers at the Medical University of South Carolina (MUSC) and the Ralph H. Johnson VA Medical Center report that inhibiting prostaglandin production slows the progression of premalignant lesions to head and neck squamous cell carcinoma (HNSCC). Preclinical studies showed that treatment of premalignant lesions with indomethacin, a nonsteroidal anti-inflammatory drug (NSAID) similar to aspirin, increased the presence of immune cells and lessened tumor burden.

Cancers of the head and neck begin with lesions in the oral cavity, including the larynx, pharynx, throat, lips, mouth, salivary glands, and nasal passages. Although the incidence of HNSCC has been on the decline over the past several decades, the National Cancer Institute reports that approximately 3% of all cancers in the U.S. result from HNSCC, with men being diagnosed twice as often as women. Treatment for HNSCC includes surgical removal and chemo-radiation treatment; however, these interventions often fail, and patients have a five-year survival rate of only 50%. It is critical to determine better treatment options for HNSCC patients.

One way researchers at MUSC are trying to improve the treatment of HNSCC is by enhancing the body’s own immune system to attack the tumor.

“There’s a lot of effort to stimulate immune reactivity using immunotherapy. The problem with that is cancer can protect itself against the immune defenses. Head and neck cancer is notorious for that,” said immunologist M. Rita Young, Ph.D., senior author for this study, who holds a dual appointment at MUSC and the Ralph H. Johnson VA Medical Center.

As an immunologist, Young has been working on addressing this problem by studying how the immune system affects tumor progression. Previous work from her laboratory has shown that the composition of immune cells within premalignant lesions differs from that within HNSCC. Significantly, as premalignant cells develop into HNSCC, the immune environment switches from stimulatory/inflammatory to immunosuppressive. This change in the tumor microenvironment prevents the immune system from combating the cancer. Prostaglandin may be an important mediator of this switch.

The current study used a novel mouse model of HNSCC to determine how inhibition of prostaglandin affects tumor progression. Mice with premalignant lesions were given indomethacin, an NSAID that inhibits the production of prostaglandin. Indomethacin treatment increased the presence of immune cells at the lesion site and led to a systemic activation of the immune system. Specifically, there was an increase in both Th1-associated cytokines (IL-2 and IFN-γ) as well as Th2-associated cytokines (IL-10). This activation of the immune system reduced the progression of premalignant lesions to HNSCC.

Future studies in this area will be focused on maintaining a strong immune presence in pre-malignant lesions for patients. If studies in humans bear out these preclinical findings, further research using more specific prostaglandin inhibitors in combination with other immunomodulatory compounds could provide a better treatment regimen to prevent the formation of HNSCC.

“Immunotherapy should be considered as a treatment strategy for premalignant lesions before they progress to cancer. We can detect them. Why not treat them?” said Young. Furthermore, these intervention strategies may be able to help prevent smaller, as yet undetectable lesions from progressing to HNSCC.

This work provides strong evidence that treatment of premalignant lesions with indomethacin reduces the tumorigenicity of HNSCC. A better understanding of the mechanisms by which the immune system combats early-stage cancer could lead to improved clinical outcomes in HNSCC, and potentially, other types of cancer as well.

“If we can be more persistent and focused on finding premalignant lesions before they become malignant, simple therapies might be beneficial,” said Sara Johnson, Ph.D., a postdoctoral fellow at MUSC and a co-author on the article.

December, 2016|Oral Cancer News|

Can your own immune system kill cancer?

Source: www.cnn.com
Author: Jacqueline Howard

screen-shot-2016-10-26-at-9-38-07-am

There was another big win in the advancement of immunotherapy treatments for cancer this week.

The Food and Drug Administration approved an immunotherapy drug called Keytruda, which stimulates the body’s immune system, for the first-line treatment of patients with metastatic non-small-cell lung cancer.

In other words, the drug could be the very first treatment a patient receives for the disease, instead of chemotherapy. Keytruda is the only immunotherapy drug approved for first-line treatment for these patients.

So it seems, the future of cancer care may be in our own immune systems, but how exactly does it work, and what are its pros and cons?

“It’s certainly going to become an independent way of treating cancers,” said Dr. Philip Greenberg, head of immunology at the Fred Hutchinson Cancer Research Center in Seattle, during a Q&A session at the International Cancer Immunotherapy Conference in New York in September.

“We always talk about the three pillars of cancer therapy — radiation therapy, chemotherapy and surgery — and it’s become quite clear now that there’s going to be a fourth pillar, which is immunotherapy,” he said. “There are times where it will be used alone, and there will be times that it will be used in conjunction with the other therapies, but there’s very little to question that this is going to be a major part of the way cancers are treated from now on, going forward.”

Here’s a look at the past, present and future of cancer immunotherapy.

It began with Bessie

In the summer of 1890, 17-year-old Elizabeth Dashiell, affectionately called “Bessie,” caught her hand between two seats on a passenger train and later noticed a painful lump in the area that got caught, according to the Cancer Research Institute.

She met with a 28-year-old physician named Dr. William Coley in New York to address the injury. He performed a biopsy, expecting to find pus in the lump, probably from an infection. But what he found was more disturbing: a small gray mass on the bone. It was a malignant tumor from a type of cancer called sarcoma.

Dashiell had her arm amputated to treat the cancer, but the disease quickly spread to the rest of her body. She died in January 1891. A devastated Coley went on to devote his medical career to cancer research.

Coley is sometimes referred to as the “father of cancer immunotherapy,” according to the Memorial Sloan Kettering Cancer Center.

During his career, he noticed that infections in cancer patients were sometimes associated with the disease regressing. The surprising discovery prompted him to speculate that intentionally producing an infection in a patient could help treat cancer.

To test the idea, Coley created a mixture of bacteria and used that cocktail to create infections in cancer patients in 1893. The bacteria would sometimes spur a patient’s immune system to attack not only the infection but also anything else in the body that appeared “foreign,” including a tumor. In one case, when Coley injected streptococcal bacteria into a cancer patient to cause erysipelas, a bacterial infection in the skin, the patient’s tumor vanished — presumably because it was attacked by the immune system.

Coley’s idea was occasionally studied by various researchers in the 1900s but was not widely accepted as a cancer treatment approach until more recently.

“Immunotherapy has essentially undergone a sort of revolution in the last decade in the sense that something that was experimental — and there were still questions about what role it would have in the way cancer is treated — is completely turned around, and now it’s clear it’s effective,” Greenberg said.

German physician Dr. Paul Ehrlich, who won the Nobel Prize in physiology or medicine in 1908, proposed using the immune system to suppress tumor formation in the “immune surveillance” hypothesis — an idea that seems to follow Coley’s.

Yet it wasn’t until the early 2000s that the hypothesis became more widely accepted, according to the Cancer Research Institute. A landmark review published in the journal Nature Immunology in 2002 supported the validity of cancer immunosurveillance.

“Cancer immunotherapy really refers to treatments that use your own immune system to recognize, control and hopefully ultimately cure cancers,” said Jill O’Donnell-Tormey, CEO of the Cancer Research Institute, during the conference in New York last month.

“Many people for many years didn’t think the immune system was really going to have a role in any treatment for cancer,” she said, “but I think the entire medical community (and) oncologists now agree that immunotherapy’s here to stay.”

‘Turning oncology on its head’

One of the most famous cancer patients to have received a form of immunotherapy is former President Jimmy Carter, who had a deadly form of skin cancer called melanoma. Last year, he announced that he was cancer-free after undergoing a combination of surgery, radiation and immunotherapy.

Carter was taking Keytruda. It’s approved to treat melanoma, non-small-cell lung cancer, and head and neck cancer. However, it’s not the only approved immunotherapy option out there.

“The advances and the results we’ve seen with using the immune system to treat cancer in the last five years or so are turning the practice of oncology on its head,” said Dr. Crystal Mackall, a professor at the Stanford University School of Medicine and expert on cancer immunotherapy.

You don’t want to overstate it. As an immunotherapist, I see things from my vantage point, which is biased, but my clinical colleagues use words like ‘revolution,’ ” she said. “When I hear them say that, I think, ‘Wow, this really is a paradigm shifting for how we think about treating cancer.’ ”

Immunotherapy comes in many forms — treatment vaccines, antibody therapies and drugs — and can be received through an injection, a pill or capsule, a topical ointment or cream, or a catheter.

The FDA approved the first treatment vaccine for cancer, called sipuleucel-T or Provenge, in 2010. It stimulates an immune system response to prostate cancer cells and was found in clinical trials to increase the survival of men with a certain type of prostate cancer by about four months.

Another treatment vaccine, called T-VEC or Imlygic, was approved by the FDA in 2015 to treat some patients with metastatic melanoma.

Some antibody therapies have been approved, as well. Antibodies, a blood protein, play a key role in the immune system and can be produced in a lab to help the immune system attack cancer cells.

The FDA has approved several antibody-drug conjugates, including Kadcyla for the treatment of some breast cancers, Adcetris for Hodgkin lymphoma and a type of non-Hodgkin T-cell lymphoma, and Zevalin for a type of non-Hodgkin B-cell lymphoma.

The FDA also has approved some immunotherapy drugs known as immune checkpoint inhibitors. They block some of the harm that cancer cells can cause to weaken the immune system.

Keytruda, which Carter took, is a checkpoint inhibitor drug. Other such drugs include Opdivo to treat Hodgkin lymphoma, advanced melanoma, a form of kidney cancer and advanced lung cancer. Tecentriq is used to treat bladder cancer, and Yervoy is used for late-stage melanoma.

Additionally, there are many immunotherapy treatments in clinical trials, such as CAR T-cell therapy. The cutting-edge therapy involves removing T-cells from a patient’s immune system, engineering those cells in a lab to target specific cancer cells and then infusing the engineered cells back into the patient. The treatment is being tested to treat leukemia and lymphoma.

“The real excitement now in cellular therapy, in T-cell therapies, is it reflects the developments in an area that we call synthetic biology, which is that you can add genes to cells and you can change what they do, how they behave, how they function, what they recognize,” Greenberg said.

The high price of new immunotherapy drugs has also garnered attention in the field, according to the Fred Hutchinson Cancer Research Center. For instance, some estimates suggest that checkpoint inhibitor treatments could cost as much as $1 million per patient.

As approvals continue, many scientists caution that doctors and patients alike should prepare for potential severe side effects and downsides.

Boosting the immune system with such therapies may cause skin reactions, flu-like symptoms, heart palpitations, diarrhea and a risk of infection. New cancer immunotherapy drugs have even been linked to arthritis in some patients.

A clinical trial conducted by Juno Therapeutics to test the effectiveness of an experimental immunotherapy treatment for lymphoblastic leukemia was halted after three patients died. They suffered cerebral edema or brain swelling.

Greenberg is a scientific co-founder of Juno Therapeutics.

However, “one of the best attributes of immunotherapy and the future of medicine is that it’s very precise in the way that it kills tissue and spares normal tissue, so in some way, immunotherapy is less toxic (than other therapies). There are patients who are treated with checkpoint inhibitors who have essentially no side effects,” Mackall said. “That would never happen with chemotherapy. They would always have side effects.

“Still, you know, the fact remains that probably nothing is perfect, and there are likely to be some side effects, but as far as we know now, they are less likely to be as severe or prevalent.”

As immunotherapy continues to develop as an option for cancer treatment, experts plan to be realistic about forthcoming challenges.

The challenges of immunotherapy

Experts say they hope to better understand why some patients may have different responses to immunotherapy treatments than others — and why some treatments may result in remissions instead of relapses, or vice versa.

“There’s this whole problem of, you give people an immunotherapy, it looks like it’s working, and then it stops working. We get recurrences or progression after some period, and the question is, why did that happen? How can you change it?” Greenberg said.

“This is where the science has come to play an important part: Is it because the immune response was working and somehow the tumor turned it off? And if that’s the case, then we have to look at ways in which we can reactivate the immune system,” he said. “Or is it not that, is it just that the immune system did what it’s supposed to do, but now a variant grew out, now a tumor grew out that’s no longer recognized by the immune response you are enforcing? If that’s the case, then we need ways to build subsequent immune responses to tackle that.”

Therefore, researchers have to better understand the behavior of not only the immune system but also cancerous tumors — and it’s no simple task.

“If there’s a perception that it’s easy, that’s a mistake. I think our lab has spent decades trying to figure out how to manipulate the immune response,” Greenberg said.

“Some patients are anticipating things to change overnight and be immediately available as a therapy. It takes quite a while,” he said, “but I’m quite certain immunotherapy is going to be enormously useful. It’s just, right now, we are limited in what can be done.”

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy

October, 2016|Oral Cancer News|

Immunotherapy drug a ‘gamechanger’ for head and neck cancer

Source: www.theguardian.com
Author: staff

An immunotherapy drug hailed as a potential gamechanger in the treatment of cancer could soon offer new hope to patients with currently untreatable forms of the disease.

Nivolumab outperformed chemotherapy significantly in keeping relapsed head and neck cancer patients alive. Photograph: Alamy

Nivolumab outperformed chemotherapy significantly in keeping relapsed head and neck cancer patients alive. Photograph: Alamy

Nivolumab was found to extend the lives of relapsed patients diagnosed with head and neck cancers who had run out of therapy options. After a year of treatment, 36% of trial patients treated with the drug were still alive compared with 17% of those given standard chemotherapy.

Trial participants treated with nivolumab typically survived for 7.5 months, and some for longer. Middle-range survival for patients on chemotherapy was 5.1 months. The phase-three study, the last stage in the testing process before a new treatment is licensed, provided the first evidence of a drug improving survival in this group of patients.

Prof Kevin Harrington, from the Institute of Cancer Research, London, who led the British arm of the international trial, said: “Nivolumab could be a real gamechanger for patients with advanced head and neck cancer. This trial found that it can greatly extend life among a group of patients who have no existing treatment options, without worsening quality of life.

“Once it has relapsed or spread, head and neck cancer is extremely difficult to treat. So it’s great news that these results indicate we now have a new treatment that can significantly extend life, and I’m keen to see it enter the clinic as soon as possible.”

Before it can be offered on the NHS, the treatment will have to be approved by the European Medicines Agency and the National Institute for Health and Care Excellence (Nice), which vets new therapies in England and Wales for cost-effectiveness.

Of the 361 patients enrolled in the trial, 240 were given nivolumab while the remaining 121 received one of three different chemotherapies. UK patients were assigned the chemotherapy drug docetaxel, the only treatment currently approved for advanced head and neck cancer by Nice.

Patients whose tumours tested positive for the HPV virus, which is linked to cervical cancer and may be spread by oral sex, did especially well. They typically survived for 9.1 months, compared with 4.4 months when treated with chemotherapy. More than half of patients relapse within three to five years.

Nivolumab is one of a new class of antibody drugs called checkpoint inhibitors that help the immune system fight cancer. It works by blocking signals from tumour cells that stop the immune system attacking.

The drug is already licensed for the treatment of advanced melanoma skin cancer and non-small-cell lung cancer in the UK. However while Nice has backed its use on the NHS for melanoma it has so far refused to recommend making the drug freely available to lung cancer patients.

Prof Paul Workman, chief executive of the Institute of Cancer Research, said: “Nivolumab is one of a new wave of immunotherapies that are beginning to have an impact across cancer treatment. This phase-three clinical trial expands the repertoire of nivolumab even further, showing that it is the first treatment to have significant benefits in relapsed head and neck cancer.

“We hope regulators can work with the manufacturer to avoid delays in getting this drug to patients who have no effective treatment options left to them.”

October, 2016|Oral Cancer News|