immunotherapy

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

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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|

HPV is changing the face of head and neck cancers

Source: www.healio.com
Author: Christine Cona
 

A drastic increase in the number of HPV-associated oropharynx cancers, particularly those of the tonsil and base of tongue, has captured the attention of head and neck oncologists worldwide.

In February, at the Multidisciplinary Head and Neck Cancer Symposium in Chandler, Ariz., Maura Gillison, MD, PhD, professor and Jeg Coughlin Chair of Cancer Research at The Ohio State University in Columbus, presented data that showed that the proportion of all head and neck squamous cell cancers that were of the oropharynx — which are most commonly HPV-positive cancers — increased from 18% in 1973 to 32% in 2005.

9ea467bbf8646a69da2a432f8fcc5452Maura Gillison, MD, PhD, Jeg Coughlin Chair of Cancer Research at The Ohio State University, said screening for HPV in the head and neck is years behind cervical screening for HPV.

 

In addition, studies from the United States, Europe, Denmark and Australia indicate that HPV-positive patients have a more than twofold increased cancer survival than HPV-negative patients, according to Gillison.

With the rising incidence of HPV-related oropharynx cancers, it will soon be the predominant type of cancer in the oral or head and neck region, according to Andy Trotti, MD, director of radiation oncology clinical research, H. Lee Moffitt Cancer Center & Research Institute, in Tampa, Fla.

“We should be focusing on HPV-related oropharyngeal cancer because it will dominate the field of head and neck cancers for many years,” he said during an interview with HemOnc Today. “It is certainly an important population for which to continue to conduct research.”

Because HPV-associated oropharyngeal cancer is emerging as a distinct biological entity, the recent rise in incidence will significantly affect treatment, and prevention and screening techniques, essentially reshaping current clinical practice.

Social change driving incidence

In the analysis performed by Gillison and colleagues, trends demonstrated that change in the rates of head and neck cancers was largely due to birth cohort effects, meaning that one of the greatest determinants of risk was the year in which patients were born.

The increased incidence of HPV-related oropharyngeal squamous cell carcinoma started to occur in birth cohorts born after 1935, indicating that people who were aged in their teens and twenties in the 1960s were demonstrating increased incidence, Gillison said.

“Two important and probably related events happened in the 1960s. In 1964, the surgeon general published a report citing smoking as a risk factor for lung cancer, and public health policy began promoting smoking cessation along with encouragement not to start smoking,” she told HemOnc Today.

If you were 40 years old between 2000 and 2005, your risk for having HPV-related cancer is more than someone who was between the age of 40 and 45 years in 1970, according to Gillison. Social changes that occurred among people born after 1935, for example, a reduction in the number of smokers, is consistent with the increasing proportion of oropharyngeal cancers that were HPV-related.

“The rates for HPV-related cancers began to increase and the rates for HPV-unrelated cancers started to decline, consistent with the known decline in tobacco use in the U.S. population,” she said.

Now, most cases of head and neck squamous cell carcinoma in non-smokers are HPV-related; however, oral HPV infection is common and is a cause of oropharyngeal cancer in both smokers and non-smokers, research shows.

In addition to a decrease in tobacco use reducing HPV-unrelated oral cavity cancers, the number of sexual partners may have increased during this time and have helped to increase HPV-related oropharyngeal cancers, according to Gillison.

Determining the cause of the elevated incidence is only a small piece of the puzzle. Screening, establishing who is at risk, and weighing vaccination and treatment options are all relevant issues that must be addressed.

Screening is problematic

A critical area for examination and research is the issue of screening for oral cancers. In contrast to cervical cancer, there is no accepted screening that has been shown to reduce incidence or death from oropharyngeal cancer, according to Gillison.

Not many studies have examined the issue of screening for HPV-unrelated oral cancers, and the few that have, tend to include design flaws.

Gillison said there is a hope that dentists would examine the oral cavity and palpate the lymph nodes in the neck as a front-line screen for oral cancer; however, in her experience, and from her perspective as a scientist, this has never been shown to provide benefit for oral cancer as a whole.

Another caveat with regard to HPV detection is that head and neck HPV screening is about 20 years behind the cervical field.

“Clinicians screening for HPV in the field of gynecology were incredibly fortunate because Pap smear screening was already an accepted cervical cancer screening method before HPV was even identified,” she said. “There was already a treatment algorithm: If there were cytologic abnormalities, patients were referred to the gynecologist, who in turn did a colposcopy and biopsy.”

A similar infrastructure does not exist for oropharyngeal cancer. People with HPV16 oral infection are at a 15-fold higher risk for oropharynx cancer and a 50-fold increased risk for HPV-positive head and neck cancer, yet there is no algorithm for treatment and management of these at-risk individuals, Gillison said.

In 2007, WHO said there was sufficient evidence to conclude that HPV16 was the cause of oropharynx cancer, but with no clinical algorithm already established, progress in this area is much further behind.

Another problematic aspect of HPV-related oropharyngeal cancer screening is that the site where the cancer arises is not accessible to a brush sampling, according to Gillison.

“To try to find this incredibly small lesion in the submucosal area that you cannot see and cannot get access to with a brush, highlights that we need to develop new techniques, new technologies and new approaches,” she said.

The near future consists of establishing the actual rates of infection in the oral cavity and oropharynx, and then screening for early diagnosis, according to Erich Madison Sturgis, MD, MPH, associate professor in the department of head and neck surgery and the department of epidemiology at The University of Texas M.D. Anderson Cancer Center.

“I am not extremely hopeful because the oropharyngeal anatomy makes screening complicated, and these cancers likely begin in small areas within the tonsils and the base of the tongue,” Sturgis told HemOnc Today. “I am hopeful, however, that preventive vaccines will eventually, at a population level, start to prevent these cancers by helping people avoid initial infection by immunity through vaccination earlier in life.”

Much of the currently known information surrounding the issue of HPV-related oral cancers is new, so researchers continue to conduct research in various relevant areas. One key question to answer is who may be at higher risk for HPV-related oropharynx cancers.

Who is at risk?

As mentioned earlier, the number of oral sex partners seems to play a role in the risk for contracting the HPV virus.

In one study published in The New England Journal of Medicine in 2007, findings demonstrated that a high lifetime number of oral sex partners (at least six partners) was associated with an increased risk for oropharyngeal cancer (OR=3.4; 95% CI, 1.3-8.8).

In addition to a higher number of oral sex partners, other still unknown factors may be contributing to risk. This is an area that needs further research, according to Barbara Burtness, MD, chief of head and neck oncology, and professor of medical oncology at Fox Chase Cancer Center in Philadelphia.

The effect of smoking status is another area that needs further research. According to Burtness, smokers with HPV-associated oropharynx cancer have less favorable outcomes.

When discussing the prognosis of HPV-associated cancers, Sturgis said low risk is defined as low or no tobacco exposure and positive HPV status, and intermediate risk is defined as significant tobacco exposure but an HPV-positive tumor, and the highest risk group appears to be the HPV-negative group.

Although HPV-negative cancers are overwhelmingly tobacco-related cancers and tend to have multiple mutations, it appears that HPV-positive cancers, particularly those in patients with low tobacco and alcohol exposure, tend to lack mutations and to have a better prognosis, and this may ultimately help to guide treatment practices, according to Sturgis. Yet, there is still much to learn about HPV-related oropharyngeal cancers on various fronts.

Vaccination a hopeful ally

In HPV-related head and neck cancer, particularly oropharynx cancers, more than 90% of patients who have an HPV-type DNA identified, have type 16, according to Sturgis.

The two current HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), which are approved for cervical cancers, include HPV types 16 and 18; therefore, in theory, they should be protective against the development of infections in the oropharynx and protective at preventing these HPV-associated cancers from occurring.

The presumption is that if there was a population-wide vaccination against HPV, there would be less person-to-person transmission, and this would lead to fewer oropharynx cancers, according to Burtness, who said this theory still needs further research.

There is excitement at the possibility that therapeutic vaccines could be developed, and various groups are investigating this, Burtness added.

“There is reason to think that the vaccines may be helpful; however, when HPV infects the tonsillar tissues, it exerts control in the host cells by making two proteins: E6 and E7; so another potentially exciting therapeutic avenue would be to target those specific viral proteins,” she told HemOnc Today.

Anxiety about protection from the HPV virus is palpable, according to Sturgis. He described the worry that many patients experience about contracting and transmitting HPV infection.

“Many patients are concerned they will put their spouses and/or children at risk in ways such as kissing them; and we need to tone down those worries until we have better data,” he said.

Screening and vaccination are fundamental aspects of current ongoing research, but of equal importance is determining what clinicians should do to treat a population of patients with HPV-related oropharyngeal cancers.

HPV status may influence treatment

With rates of HPV-related cancers escalating, determining the appropriate treatment for these patients is crucial.

During the past 10 years, findings from retrospective studies have shown that patients with HPV-related cancers have a much better prognosis than patients who test negative for HPV. Findings from several retrospective analyses from clinical trials conducted during the past 2 years have come to the same conclusion, according to Gillison: HPV-positive patients have half the risk for death compared with patients negative for HPV.

Therefore, there may be several alternative treatment options, including the possibility of reducing the dose of radiation given to patients after chemotherapy, thereby reducing toxicity.

Comparing HPV-negative and HPV-positive patients may not be enough to determine proper treatment, researchers said. Data between different cohorts of HPV-positive patients also needs to be examined. Smoking, for example, may play a role in patient outcome.

In a prospective Radiation Therapy Oncology Group clinical trial (RTOG 0129), presented by Gillison at the 2009 ASCO Annual Meeting and recently published in The New England Journal of Medicine (see page 53), researchers conducted a subanalysis of the effect of smoking on outcome in uniformly staged and treated HPV-positive and HPV-negative patients while accounting for a number of potential confounders. HPV-positive patients who were never smokers had a 3-year OS of 93% compared with heavy smoking HPV-negative patients who had an OS of 46%.

The study found that smoking was independently associated with OS and PFS. Patients had a 1% increased risk for death and cancer relapse for each additional pack-year of smoking. This risk was evident in both HPV-positive and HPV-negative patients. Gillison said smoking data must be paid attention to, and she encouraged cooperative group research on the topic.

Most of the findings demonstrate improved outcomes for patients with HPV-positive oropharyngeal cancers vs. patients with HPV-negative oropharyngeal cancers, according to the experts interviewed by HemOnc Today.

Dose de-intensification for less toxicity

To date, there is no evidence that HPV-related cancers should be managed differently than HPV-unrelated cancers, but it is a hot topic among clinicians in the field, according to Burtness.

The superior outcomes for HPV-associated oropharynx cancer have suggested the possibility of treatment de-intensification. The use of effective induction chemotherapy may permit definitive treatment with a lower total radiation dose. In theory, this would reduce the severity of late toxic effects of radiation, such as swallowing dysfunction. Such a trial is being conducted by the Eastern Cooperative Oncology Group. Burtness said this is currently pure research question.

“There is still much research that needs to be done before clinicians can safely reduce the dose of radiation administered to HPV-positive patients,” Burtness said.

Currently, she and colleagues in the ECOG are conducting a study of patients with HPV-associated stage III or IV oropharynx cancers to examine the possibility of tailoring therapy to these patients. Patients are assigned to one of two groups: low-dose intensity-modulated radiotherapy 5 days per week for 5 weeks (27 fractions) plus IV cetuximab (Erbitux, ImClone) once weekly for 6 weeks, or standard-dose intensity-modulated radiotherapy 5 days per week for 6 weeks (33 fractions) plus IV cetuximab once weekly for 7 weeks.

If patients have a very good clinical response to chemotherapy, which is likely to happen with HPV-associated cancers, they are eligible to receive a reduced dose of radiation, and hopefully, they would experience less adverse effects, Burtness said.

“Patients who are treated with the full course of radiation for head and neck cancer are now getting 70 Gy, and they are often left with dry mouth, and speech and swallowing difficulty,” she said. “We are hopeful that if these particular cancers are treatment responsive to chemotherapy, we may be able to spare the patient the last 14 Gy of radiation.”

Immunotherapy a viable treatment

Another possible treatment technique that may benefit patients with HPV-related cancers is immunotherapy. One form of immunotherapy uses lymphocytes collected from the patient, and training the cells in the laboratory to recognize in this case a virus that is associated with a tumor and consequently attack it. This approach potentially may be used to treat HPV-related oropharynx cancers, according to Carlos A. Ramos, MD, assistant professor at the Center for Cell and Gene Therapy at Baylor College of Medicine, Houston.

“With some infections that lead to cancer, even though the virus is present in the tumor cells, the proteins shown to the immune system are limited; therefore, they do not drive a very strong immune response,” Ramos told HemOnc Today. “Training the immune system cells, T lymphocytes, may make them respond better to antigens.”

Data from ongoing trials that are taking T lymphocytes from patients and educating them to recognize antigens in patients with the Epstein-Barr virus associated tumors have shown some activity against them, according to Ramos. This adoptive transfer appears to be safe and may have the same effect on the HPV virus associated tumors. Immunotherapy does not cause the usual toxicities associated with chemotherapy, he said.

“There are currently no trials showing whether we can prevent more recurrences with this approach, but the results of trials examining viruses such as Epstein-Barr are good so far, in both patients who have no evidence of disease and in those who still have disease,” he said.

Even patients with active disease who have not responded to other therapies have responded to this therapy, Ramos said. He and colleagues are working toward compiling preclinical data to study the possibility of using immunotherapy to treat patients with HPV-related cancers.

Journey is just beginning

Much of what is known about risk, screening, prevention and treatment of HPV-related oropharynx cancers is in the early stages of discovery and much is still theoretical, according to Sturgis.

“As far as we can tell, these infections are transmitted sexually; the hope is that as we have better vaccines for prevention of cervical dysplasia, the downstream effect will help prevent other HPV-related cancers, such as anal cancers and penile cancers and oropharyngeal cancers,” he said.

Several recent studies examining new therapies that may reduce the intensity of traditional treatments while maintaining survival rates would have a major effect on the field, according to Sturgis.

Gillison said the rise in the number of cases of HPV-related cancers is changing the patient population considered to be at risk, and more research is vital.

“The most important thing for clinicians to do is be aware that trials are being developed and strongly encourage their patients to participate,” she said.  Christen Cona

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

June, 2016|Oral Cancer News|

Checkpoint inhibitors seen to show potential of immunotherapy in several cancer studies

Source: immuno-oncologynews.com
Author: Magdalena Kegel

Several new checkpoint inhibitors — a class of immunotherapy drugs used in cancer — continue to show beneficial effects in numerous cancer types, according to data presented at the recent American Association for Cancer Research Annual Meeting in New Orleans.

Investigated checkpoint inhibitors confirmed earlier results showing evidence of efficacy in melanoma, and also suggested that this class of immunotherapies, which trigger a person’s immune system to attack cancer, might work in patients suffering from certain head and neck cancers.

One of the studies, CheckMate-141, exploring the checkpoint blocker nivolumab (Opdivo) in patients with squamous cell carcinoma of the head and neck, was stopped early after 36 percent of the 361 patients survived for one year — an increase of more than 100 percent compared to patients receiving other treatments.

Squamous cell carcinoma is usually treated with platinum-based chemotherapy, but the effects are often temporary as the cancer tends to return. Moreover, patients who fail to fully recover after chemotherapy are generally resistant to further treatment.

Maura Gillison from Ohio State University, who presented the CheckMate-141 data, said that no effective treatments have been approved for patients with this kind of cancer in over a decade. “I’ve treated head and neck cancers for more than twenty years, and this is the first time I’ve had a drug to go to for patients that have become resistant to first-line treatment,” she said in a press release.

Dr. Emma King, a Cancer Research UK-funded head and neck cancer expert, added that the findings are likely to have a “significant impact” for these cancer patients. “They also reinforce the important shift that we are seeing towards using immunotherapies for cancer treatment.”

“Before nivolumab can be used routinely to treat head and neck cancer in the UK, it will need to approved by the National Institute for Health and Clinical Excellence (NICE),” she added.

Nivolumab was investigated in the CheckMate-069 trial, where its efficiency in advanced melanoma was tested in combination with another checkpoint inhibitor, ipilimumab (Yervoy).

Data presented showed that 60 percent of patients on the combination therapy survived for two years. But the benefit can come with a high price, as severe side effects forced one-third of patients to stop the treatment.

“Both nivolumab and ipilimumab have changed survival expectations in advanced melanoma over the last few years, and these latest data show us that combining these two immunotherapies is an effective two-pronged attack against the cancer,” said Dr. James Larkin, a medical oncologist at the Royal Marsden Hospital.

Yet another study found nivolumab to increase five-year survival in advanced melanoma patients to one-third — again, a doubling compared to what can be achieved by conventional treatment.

Merkel cell carcinoma, a rare skin cancer linked to exposure to a common virus, was also among the cancer types showing benefits from checkpoint inhibitor treatment. Once the cancer spreads, no treatments are effective in holding it back. The checkpoint blocker pembrolizumab (Keytruda) caused tumors to shrink in about half of the 26 patients in the trial.

“The trial also suggests that patients whose Merkel cell carcinoma is linked to a virus may be more likely to benefit from this treatment, which fits with the idea that the more danger signals there are in a cancer, the easier it is for the immune system to recognise it,” said Peter Johnson, Cancer Research UK’s chief clinician.

Early data of checkpoint inhibition in liver and advanced bowel cancer, used in combination with radiofrequency ablation treatment, also showed promising results.

BMS gets US breakthrough status for head & neck cancer

Source: pharmatimes.com
Author: Selina McKee

US regulators have awarded Bristol-Myers Squibb’s immunotherapy Opdivo a breakthrough designation for the potential indication of recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). The move, which should help expedite the drug’s development and review, comes after preliminary clinical evidence indicated it could offer a substantial survival benefit to patients with the condition who have already received platinum-based therapy.

A first look at the data from the Phase III CheckMate-141 trial, stopped early in January 2016 after meeting its primary endpoint of overall survival, showed that patients treated with Opdivo (nivolumab) experienced a 30 percent reduction in the risk of death compared to the investigator’s choice of therapy (methotrexate, docetaxel, or cetuximab), with a median overall survival of 7.5 months versus to 5.1 months.

Safety signals were also looking good, with treatment-related adverse events (TRAEs) of any grade occurring in 58.9 percent of patients on Opdivo versus 77.5 percent of patients on investigator’s choice. Grade 3-4 TRAEs were reported in 13.1 percent of patients on Opdivo compared to 35.1 percent taking the investigator’s choice, while two drug-related deaths were reported as related to Opdivo (pneumonitis and hypercalcaemia), and one Grade 5 event of lung infection in the comparator arm.

The findings are particularly pertinent given the particularly bleak outlook for patients whose disease has progressed after platinum therapy and lack of systemic therapies to improve survival, and thus significant unmet medical need for new options.

Head and neck cancer is the seventh most common cancer globally, with an estimated 400,000 to 600,000 new cases per year and 223,000 to 300,000 deaths per year. The five-year survival rate is reported as less than 4% for metastatic Stage IV disease.

Opdivo is already available in the US to treat certain forms of melanoma, non-small cell lung cancer and renal cell carcinoma. This marks its fifth breakthrough designation from the FDA, and follows that for classical Hodgkin lymphoma issued just days ago.

April, 2016|Oral Cancer News|

Study supports immunotherapy/radiation combo in head and neck cancer

Source: www.onclive.com
Author: Laura Panjwani

There may be potential synergy between radiation therapy, given with or without chemotherapy, and immune checkpoint inhibitors in patients with squamous cell carcinoma of the head and neck (SCCHN), according to results of a prospective study.

The study, which was presented at the the 2016 Multidisciplinary Head and Neck Cancer Symposium in February 2016, examined blood samples from 16 consecutive patients with SCCHN undergoing curative-intent radiation therapies.

Samples were obtained at week 1 and week 6 to 7. Patients received a median of 70 Gy for disease in the oropharynx (n = 12, 75%), nasopharynx (n = 2, 12%), larynx (n = 1, 6%), or oral cavity (n = 1, 6%). The majority of patients had stage IV disease that was metastatic to regional lymph nodes and received concurrent platinum-based chemotherapy.

The analysis found that, during radiation treatment, circulating CD8-positive T-effector cells increased (P = .01), as did CD4-positive PD-1–positive cells (P = .02), CD8-positive LAG3-positive cells (P = .02), and regulatory T cells (P = .04). sPD-L1 levels also increased, mirroring increases in CD8-positive T cells over the course of therapy (P = .047).

While the extent to which these systemic changes reflect changes in the tumor microenvironment is unknown, the study authors noted that these findings support the “complex immunologic effects of fractionated chemoradiation therapy and mechanisms for potential synergy between chemotherapy, radiation treatment, and immunotherapy in SCCHN.”

To learn more about the impact of the research, OncLive spoke to one of the study’s authors, Jonathan D. Schoenfeld, MD, physician, assistant professor of Radiation Oncology, Harvard Medical School, Dana-Farber Cancer Institute, who presented the findings at the meeting.

OncLive: What were the goals of this study?

Schoenfeld: Immunotherapy, particularly immune checkpoint blockade, is demonstrating some exciting results in head and neck cancer. Largely, that work has been done in metastatic head and neck cancer. Our goal was to look at the immunologic effects of a treatment that is commonly given to patients with early-stage head and neck cancer: chemotherapy and radiation.

We found that the combination of chemotherapy and radiation—and in some cases, just radiation alone—led to immune effects that we could see not just in the site where we were radiating, but also if we looked at markers in the peripheral blood.

One of the interesting things that we found was that radiation, with or without chemotherapy, has the potential to increase the number of tumor antigens that were targeted by the host immune response. One of the ways that we hope to use radiation in the future is to stimulate an initial immune response.

Based on the data that is emerging with PD-1 inhibitors, we know that the majority of patients will not respond to these agents. We need to determine if we can use radiation and chemotherapy to increase the number of responders initially that can then be stimulated even further with immune checkpoint blockade.

What immune effects were investigated?
We looked at a variety of effects. We looked at chemokines, which are cytokines that could mediate effects outside of the radiation treatment field. We looked at circulating T cells, including CD8-positive T cells, CD4-positve T cells, and markers of activated T cells.

We also looked at potentially inhibitory T cells as well, including T-regulatory cells, T cells that were expressing checkpoint receptors, and myeloid-derived suppressor cells. We also looked, in more detail, at the types of T-cell receptors that were expressed on the surface of these T cells, and it looked like the combination of radiation and chemotherapy could change the clonality of the receptor on these T cells, suggesting that radiation or targeted tumor death could stimulate a more targeted immune response.

What can a community oncologist take away from these findings?

Chemotherapy and radiation have long been appreciated for their immunosuppressive effects. We all know that when you treat someone with radiation or chemotherapy, you can see a decrease in cytopenia and lymphocytes.

We are now learning that certain types of chemotherapy and radiation, given in the proper circumstance, can cause immunogenic cell death. That can possibly synergize with the newer types of immune checkpoint blockade that are being developed.

One of our study’s findings was that we saw an increase in T cells expressed in the PD-1 receptor. Those could potentially be targeted with new checkpoint inhibitors that target the PD-1 receptor. As we develop these therapies even further, there are exciting new combinations between immunotherapies and some of the traditional therapies that have long been used for head and neck cancer with potential.

In melanoma, there are case reports of patients who have progressed on immune checkpoint blockade and are then treated with high-dose palliative radiation that then began to experience a response outside of the radiation treatment field. That is a very exciting avenue of research for head and neck cancer, as well. Can we take patients who don’t respond to the current checkpoint inhibitors that we have and use radiation in a targeted way to stimulate a broader immune response?

Radiation and chemotherapy are a backbone of some of the definitive treatments currently used for head and neck cancer. There is a lot of interest with the success of PD-1/PD-L1 inhibitors to integrate these into the definitive management, and combine them the proper way with chemotherapy and radiation to better maximize our results.

Chemotherapy and radiation are still very important for patients with curative head and neck cancer, but perhaps we should be giving these treatments in a different way—different types of radiation and chemotherapy and different targets for radiation. All of these things need to be explored, as new therapies, such as immune checkpoint inhibitors, are developed in this disease.

What impact will immunotherapy will have in head and neck cancer?
It will have a huge impact. Exciting data are emerging in metastatic head and neck cancer that show that PD-1 inhibitors offer real benefit to patients. Many of these patients had very few other treatment options and could obtain a survival benefit after treatment with PD-1 inhibitors. That opens up a whole new realm of opportunities to study immunotherapy in different settings, in different groups of patients, and in combination with other agents.

Source:
Sridharan V, Margalit D, Curreri S, et al. Systemic immunologic effects of definitive radiation in head and neck cancer. Presented at: 2016 Multidisciplinary Head and Neck Cancer Symposium; February 18-20, 2016; Scottsdale, AZ. Abstract 2.

April, 2016|Oral Cancer News|

Why a Cure For Cancer Is Possible

Source: www.fortune.com
Author: Robert Mulroy
 

BERLIN, GERMANY - SEPTEMBER 05:  A doctor holds a stethoscope on September 5, 2012 in Berlin, Germany. Doctors in the country are demanding higher payments from health insurance companies (Krankenkassen). Over 20 doctors' associations are expected to hold a vote this week over possible strikes and temporary closings of their practices if assurances that a requested additional annual increase of 3.5 billion euros (4,390,475,550 USD) in payments are not provided. The Kassenaerztlichen Bundesvereinigung (KBV), the National Association of Statutory Health Insurance Physicians, unexpectedly broke off talks with the health insurance companies on Monday.  (Photo by Adam Berry/Getty Images)

Cutting drug prices is not out of the question.

A crapshoot is defined as a risky or uncertain matter; something that could produce a good or bad result. President Obama’s moonshot on cancer is different in terms of its greater complexity and higher moral purpose — but unfortunately, not in its probability of success.

The Audacity of Scope

President Obama has asked Congress for $755 million to “focus” on immunotherapy, combination therapy, vaccines that prevent cancer causing viruses, and early detection techniques. According to Vice President Joe Biden, who will coordinate 13 government institutions in this research, “Our job is to clear out the bureaucratic hurdles, and let science happen.”

It is hard not to welcome such an initiative. Cancer has deposed heart disease as the number one killer in 22 American states. Experts project the number of global cancer cases will double in the next 15 years. But we are better at projecting the demand for innovation than we are at producing it; and we are even better at making promises we can’t keep and polices that don’t work.

President Roosevelt created the National Cancer Institute in 1937. Nixon declared a “war on cancer” with the National Cancer Act in 1971. The Bush administration spoke in 2003 of spending $600 million per year to rid the world of cancer by 2015. Obama and Biden made campaign promises to fight cancer in 2008, and should be lauded for trying to keep them, but their approach needs a lot of work.

The underlying assumption is that we should spend as much money, and use as many public and private constituencies to do as much as we can on as many paths as possible. There are three things wrong with this: first, $755 million is a measly sum under the current paradigm drug development. It can cost a company up to $5 billion and a full decade to bring one cancer-fighting drug to market. Second, we have tried this strategy before. Doing the same thing again, only harder, will lead to numerous failures whose cost will be passed on to the insurance companies and their customers in the form of high drug prices. Third, the answer is right in front of us.

We use the term moonshot to reference JFK’s successful space program, but don’t apply its deepest insights. We in the cancer fighting community lack that program’s predictive models, which were the key to its success. Despite severe technological limitations, NASA believed in predictive models based in math, engineering and physics. They modeled, for example, gravity’s influence on earth launches, moon landings, and human tissue. The models told them exactly what tools were needed to do the job. Only then did they build spacecraft to accomplish our goals.

Meanwhile, back on earth, we build tools before we understand the problem of cancer. Two-thirds of published research cannot be reproduced. In the post-genomic era, the FDA approves only 7% of drugs that enter cancer clinical research. Over the past five years, twice as many trials have resulted in only a 10% increase in approvals. Industry investment in R&D has gone backwards, and with it comes a soaring cost of innovation that drives drug prices. Imagine the public tumult, the demand for our leaders to resign, if only one in 14 of rockets carried our astronauts safely!

Great Strategy is Reconciling what Others Believe are Opposites

The discussion we should be having is how to cure cancer and lower drug prices at the same time. Cancer is a multidimensional, ever-changing disease of the entire cell system. The standard focus on individual targets — while supporting publications to drive academic careers and intellectual property that supports high-risk industry investment — has failed. The secrets of biology lay in the interactions between molecules: the dynamics. We need to hack into a human cell as if it were a computer and decode the operating system: switch these proteins off to cure pancreatic cancer, turn others on to end heart disease, and deliver smart growth factors to regenerate neural tissue.

If predictive engineering was the impetus behind space travel, then systems biology can spur innovation and foster initiatives of “cell exploration.” Systems biology is the method of building models of complex biological environments so we can design the right drug from the start. These drugs would have fewer off-target effects and last longer at the disease site. They would also cost less because the cost of failure of the present “scattershot” system of drug discovery would not be passed along to the consumer.

The NIH is a national treasure that houses the tiny National Centers for Systems Biology, a network of our top academic institutions and thought leaders who are already on the path to uncovering cellular secrets. But last year, of the $25 billion in grants supported by the NIH, those aimed at the truly transformational opportunity of systems biology totaled a mere $8 million, or .032% of the total.

Many of us now know that a “war on cancer,” campaign promises massive infusions of capital, top-down political coordination and even the genomic revolution do not come close to the value created by a greater understanding of systems biology. If we call it a moonshot, but don’t comprehend the real key to putting a man on the moon, how is that different than a crapshoot?

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

March, 2016|Oral Cancer News|

Immunotherapy Continues to Advance in Head and Neck Cancer

Source: www.onclive.com
Author: Megan Garlapow, PhD
 

Concomitant administration of motolimod with cetuximab (Erbitux) increases the innate and adaptive immune response in the blood and the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC), overcoming negative prognostic biomarkers of cetuximab therapy alone, according to the biomarker data from a recent phase Ib clinical trial that was presented at the 2016 Head and Neck Cancer Symposium. The trial was recently amended to add nivolumab to the combination of cetuximab and motolimod.

Robert-FerrisDr. Robert Ferris, MD PhD

 

“We know that PD-1 and PD-L1 are overexpressed in head and neck cancer, and so it was somewhat irresistible to combine our baseline treatment of cetuximab and motolimod with the PD-L1 inhibition pathway. EGFR itself drives PD-L1, so combining cetuximab with anti-PD-1 inhibitor makes sense. So, we’ve amended this trial. We’re now accruing to treatment with cetuximab, motolimod, and the anti–PD-L1 nivolumab in this trial,” said lead author Robert Ferris, MD, PhD, professor, Departments of Otolaryngology, Radiation Oncology, and Immunology, Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.

According to the authors of the phase Ib data presented at the symposium, the rationale for combining cetuximab with motolimod (VTX2337) as neoadjuvant therapy was that cetuximab induces cellular immunity that correlates with neoadjuvant clinical response. The phase I dose-escalation and safety of the combination had been established (NCT 01334177).

This study of neoadjuvant cetuximab and motolimod had accrued 14 patients with HNSCC that was stage II-IV, resectable, and located in the oropharynx, oral cavity, hypopharynx, or larynx. These patients were biopsied, treated with cetuximab and motolimod for 4 weeks, and then underwent surgery. The endpoints of the trial were the modulation of immune biomarkers.

Interferon-inducible cytokine IP-10 increased after the patients were administered neoadjuvant cetuximab and motolimod (P = .0001). After the neoadjuvant treatment, the peripheral blood lymphocytes had an increased frequency of EGFR-specific CD8 T cells. After the neoadjuvant treatment, regulatory T cells had decreased suppressive receptors and transforming growth factor-β, which induces Foxp3. Also, after the neoadjuvant treatment, circulating MDSCs had decreased PD-L1 (P <.07) and macrophages had increased CD16 expression (P <.07).

After the neoadjuvant treatment with cetuximab and motolimod, genotyping of T-cell receptors showed increased clonality in peripheral blood lymphocytes (P = .003 by Wilcox signed rank test) and tumor-infiltrating lymphocytes (P = .081 by Wilcox signed rank test). Most patients are more oligoclonal than healthy individuals, and some are very clonal with highly prominent expanded clones. Genotyping of T-cell receptors found that clonality was increased by the combination of cetuximab and motolimod compared with treatment with cetuximab alone.

Recent studies have indicated that the PD-1/PD-L1 pathway is upregulated in the HNSCC microenvironment, and that EGFR blockade prevents interferon-γ-mediated upregulation of PD-L1. Thus, this study has been amended to add nivolumab to the adjuvant treatment with cetuximab and motolimod. The endpoints are still the modulation of immune biomarkers.

The aim is to target the tumor microenvironment, such that tumor immune escape is reversed and T cells eliminate HNSCC. Antitumor T cells are reprogrammed to reverse inhibitory signals. Combining the toll-like receptor agonist, motolimod, with cetuximab and with PD-1 pathway inhibitors, such as nivolumab, may enhance the priming and activity of T cells.

“Targeting the tumor microenvironment requires understanding as well as reversal of immune escape mechanisms in the cellular compartment. Reprogramming antitumor T cells to reverse inhibitory signals can be done by directly disrupting those inhibitory signals, the so-called checkpoint receptor field, and can be done potentially by combining proinflammatory signals, such as toll-like receptor agonists, to chemo-attract cells into the microenvironment and to create good inflammation to overcome suppressive factors,” said Ferris.

Recent findings have shown tremendous promise for nivolumab in head and neck cancer. Bristol-Myers Squibb (BMS) announced in January 2016 that nivolumab improved overall survival versus investigator’s choice of therapy for patients with platinum-refractory squamous cell carcinoma of the head and neck in the phase III CheckMate-141 trial. Findings from the study are being discussed with the FDA and other health authorities, according to BMS.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
February, 2016|Oral Cancer News|

Excitement at new cancer treatment

Source: www.news.doximity.com
Author: James Gallagher
_88291939_c0151810-acute_lymphoblastic_leukaemia,_micrograph-splA therapy that retrains the body’s immune system to fight cancer has provoked excitement after more than 90% of terminally ill patients reportedly went into remission.

 

White blood cells were taken from patients with leukaemia, modified in the lab and then put back.

But the data has not been published or reviewed and two patients are said to have died from an extreme immune response.

Experts said the trial was exciting, but still only “a baby step.”

The news bubbled out of the American Association for the Advancement of Science’s annual meeting in Washington DC.

The lead scientist, Prof Stanley Riddell from the Fred Hutchinson Cancer Research Centre in Seattle, said all other treatments had failed in these patients and they had only two-to-five months to live.

He told the conference that: “The early data is unprecedented.”

Re-training

In the trial, cells from the immune system called killer t-cells were taken out of dozens of patients. The cells normally act like bombs destroying infected tissue.

The researchers genetically modified the t-cells to engineer a new targeting mechanism – with the technical name of chimeric antigen receptors – to target acute lymphoblastic leukaemia.

Prof Riddell told the BBC: “Essentially what this process does is, it genetically reprograms the T-cell to seek out and recognise and destroy the patient’s tumour cells.

“[The patients] were really at the end of the line in terms of treatment options and yet a single dose of this therapy put more than ninety percent of these patients in complete remission where we can’t detect any of these leukaemia cells.”

But one cancer expert told me they still felt in the dark on the full significance of the study, as the data is not available.

Also seven of the patients developed cytokine release syndrome so severe that they required intensive care, and a further two patients died.

While those odds may be acceptable if facing terminal cancer, the side-effects are much greater than conventional leukaemia treatments such as chemotherapy and radiotherapy, which work in the majority of patients.


Analysis

By James Gallagher, health editor, BBC News website

The field of immunotherapy – harnessing the immune system to attack cancer – is coming of age.

The significance of today’s development is hard to ascertain while the data is unpublished – but the field is undoubtedly making giant strides.

Drugs called checkpoint inhibitors, such as pembrolizumab and ipilimumab, take the brakes off the immune system so it attacks cancer.

They are already being used by doctors.

And other experimental techniques are coming to fruition to allow doctors to change a patient’s own cells to engineer a designer immune system to kill cancer.

It’s an exciting time that is likely to see immunotherapy soon join chemotherapy, radiotherapy and surgery as major weapons in the fight against cancer.


There is also a big difference between using such approaches on a blood cancer like leukaemia and “solid” tumours such as breast cancer.

Dr Alan Worsley, from Cancer Research UK, said that while the field was incredibly exciting, “this is a baby step”.

He told the BBC: “We’ve been working for a while using this type of technology, genetically engineering cells. So far it’s really shown some promise in this type of blood cancer.

“We should say that in most cases standard treatment for blood cancer is quite effective, so this is for those rare patients where that hasn’t worked.

“The real challenge now is how do we get this to work for other cancers, how do we get it to work for what’s known as solid cancers, cancers in the tissue?”

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

**Note: While OCF has included this general media news report in our oral cancer news feed, we wish our readers to note the many caveats in it. A few patents had extreme reactions to the immuno therapy, including death. And the data has not been published, so outside of the group that conducted this research, there have been no professional commentaries on the trial, which perhaps might offer counterpoints. Also, for us in the oral and oropharyngeal  world of solid tumors we have no idea if this could work. Certainly these patients with only months to live, thought like I would. Why not try, I might win the lottery (as some certainly did) and if it doesn’t work, I have in my demise provided scientific insight that might help others behind me on this path.  But even in that group we do not yet know if these remissions will be robust and durable over a long period of time, or if there are to be in the coming years some new catastrophic issue related to the treatment. This is indeed an exciting time in cancer research. But as OCF continues to put stories and actual clinical data about these approaches up in our news stream, please remember that we are in the infancy of our knowledge and understanding of all this. These are not currently first line treatment ideas, many will be in the realm of clinical trial settings for years, and not available to most. While I am very fortunate to sit on the National Cancer Institute Oversight Committee on Immunotherapeutics  in Head and Neck Cancers, I was reminded the other day by a colleague trying to keep my expectations in perspective. He said – remember the charts that were available to Columbus when he set sail for the new world.  Out in the middle of the ocean there was a notation that said “Beyond here there be sea monsters…… as many ships had set to sea and many were never heard from again. And we are finding ourselves in slightly similar circumstances. Chimera antigens, and much more are giving us a glimpse of what MAY be just over the horizon.  Fortunately, I said….he landed safely on a new land, and the world that was known was changed forever.  These are indeed exciting times of great promise, but there is hard work to do still on the table.  OCF and its donor supported researchers are on the cutting edge of the current thoughts, and all of us together will hopefully find ourselves standing on that distant shore, and the world we know today will be forever changed.  Brian Hill

February, 2016|Oral Cancer News|