New oral cancer treatment used in study shrank tumors in mice by half

Thu, Sep 22, 2016

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Source: www.ksat.com
Author: Courtney Friedman – VJ, Reporter

Oral cancer is a scary diagnosis. Sixty percent of people are diagnosed in a late stage of the disease, meaning their survival rate is below 50 percent.

“These statistics have not changed in over 40 years, because there’s not been any new therapies that target oral cancers,” said Dr. Cara Gonzales, a professor of dentistry, with the UT Health Science Center of San Antonio.

A full year after single mom Paige Lewis found a small painful spot on her tongue, she was finally diagnosed with oral cancer. By that time, it was almost at stage three.

“It was a 12-hour surgery just to remove part of my tongue. They took half my tongue,” Lewis said.

The cancer, thankfully, had not spread to her lymph nodes, but the tumor was very big, meaning an invasive surgery was needed.

“They had to take so much of my mouth itself. They couldn’t get a large enough margin around the tumor itself to be sure that they got all of the cancer,” Lewis said.

That’s why she had to undergo radiation to kill the rest of the cancer cells. It worked and she’s now in remission, but radiation leaves behind lifelong complications.

“Now I have no saliva because my salivary glands were damaged from radiation,” Lewis said, with her water bottle in hand. She needs to take sips constantly to keep her mouth moist. “I have high-risk for dental infections and problems because my jaw is weaker and deteriorated.”

Lewis said her quality of life could be better if there had been other treatments available when she was diagnosed. The problem is when patients are diagnosed with late stage oral cancer, it’s typically too late for chemotherapy. Some late stage oral cancers are even inoperable.

Thanks to a new study recently released by Gonzales, new treatment for these tumors could be around the corner. The study was published in the August edition of Oral Oncology. In the study, Gonzales combined two different FDA approved treatments that have never been used together to attack oral cancer tumors.

“Our study tested whether anaplastic lymphoma kinase (ALK) inhibitors can decrease tumor growth and progression using a mouse model. There’s another pathway called epidermal growth factor receptor that lots of pre-clinical and clinical trials have been done with inhibitors targeting it,” Gonzales explained.

Each treatment individually has not affected late stage tumors. However, when Gonzales used them together, there was huge success in mice.

“In the mouse model, we did a combination treatment and that resulted in a 50 percent reduction in tumor volume within 14 days,” she said.

This treatment could be used to shrink the tumor if it’s inoperable or shrink it before surgery. It can also be used to kill remaining cancer cells after surgery. That’s an option Lewis would have chosen.

“I might not have ever needed radiation,” Lewis said.

Lewis hopes in the future, this type of treatment can be available for patients going through what she’s been through.

Though the treatment will need to face more trials before it could be approved, researchers say it’s an enormous step, and the first of its kind in four decades. Gonzales and Lewis both emphasized prevention is key. Catching oral cancer early gives someone a 90 percent survival rate.

The National Institute of Dental and Craniofacial Research lists several warning signs of oral cancer. The first is a lesion in the mouth. There are two types. Two lesions that could be precursors to cancer are leukoplakia (white lesions) and erythroplakia (red lesions). Although less common than leukoplakia, erythroplakia and lesions with erythroplakic components have a much greater potential for becoming cancerous. Any white or red lesion that does not resolve itself in 2 weeks should be reevaluated and considered for biopsy to obtain a definitive diagnosis.

The NIDCR lists other possible signs and symptoms as: a lump or thickening in the oral soft tissues, soreness or a feeling that something is caught in the throat, difficulty chewing or swallowing, ear pain, difficulty moving the jaw or tongue, hoarseness, numbness of the tongue or other areas of the mouth, or swelling of the jaw that causes dentures to fit poorly or become uncomfortable. If these problems persist for more than two weeks, a thorough clinical examination and laboratory tests, as necessary, should be performed to obtain a definitive diagnosis. If a diagnosis cannot be obtained, referral to the appropriate specialist is indicated.

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HPV symptoms and health consequences

Tue, Sep 20, 2016

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Source: www.kristv.com
Author: Roland Rodriguez

No one dreams of walking into his or her doctor’s office and hearing the words “you have been diagnosed with human papillomavirus, or HPV.” Unfortunately, this scenario is all too real.

HPV is the most common sexually-transmitted infection (STI) in the United States. In fact, it’s so common that nearly all sexually active men and women get it at some point in their lives.

There are over 100 different kinds of HPV but only some of them can cause serious health problems like genital warts or cancer of the cervix, vagina, vulva or anus.

Testing positive for HPV does not automatically mean you will get cancer. Some studies estimate that 50 percent of those infected with HPV will clear the virus within eight months— and 90 percent will be cured within two years. It’s only when your immune system isn’t able to fight off the infection that some strains of HPV can persist and possibly lead to cancer.

The number of human papilloma virus (HPV)-associated cancers in the United States has increased by 17 percent, to nearly 39,000 cases a year, according to a report released from the Centers for Disease Control and Prevention.

While men cannot get HPV-linked cervical cancers, they are particularly vulnerable to HPV-related cancers of the mouth, tongue and throat, called oropharyngeal cancers. According to the new CDC report, the rates of mouth and throat cancers are more than four times higher among males than females.

In the past, people always felt that the boys needed to be vaccinated to protect the girls but, truthfully, the most effective way to prevent HPV: early vaccination.

Boys and girls are supposed to get three doses of the HPV vaccine — starting at age 11 or 12 because the vaccine works best before sexual activity begins.

The other benefit of giving it early is that our immune response is better, and that it may last longer.

Yet the latest statistic from the CDC shows that in 2014, only 40 percent of teenage girls received all three doses of the vaccine needed. In boys, that number is even lower: Only 22 percent of boys between 13 and 17 are properly vaccinated against HPV, increasing their chances for HPV-caused cancers later in life.

According to the CDC, the HPV vaccine — which is usually covered by insurance — is safe and not associated with serious side-effects of the HPV.

What are the signs, symptoms and health consequences of HPV?

In most cases, HPV goes away on its own and does not cause any health problems. But when HPV does not go away, it can cause health problems like genital warts and cancer.

Genital warts usually appear as a small bump or groups of bumps in the genital area. They can be small or large, raised or flat, or shaped like a cauliflower. A healthcare provider can usually diagnose warts by looking at the genital area.

Cervical cancer usually does not have symptoms until it is quite advanced, very serious and hard to treat. For this reason, it is important for women to get regular screening for cervical cancer. Screening tests can find early signs of disease so that problems can be treated early, before they ever turn into cancer.

Other HPV-related cancers might not have signs or symptoms until they are advanced and hard to treat. These include cancers of the vulva, vagina, penis, anus, and oropharynx (cancers of the back of the throat, including the base of the tongue and tonsils.

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Incisionless robotic surgery offers promising outcomes for oropharyngeal cancer patients

Sun, Sep 18, 2016

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Source: medicalxpress.com
Author: press release, Henry Ford Health System

A new study from researchers at Henry Ford Hospital finds an incisionless robotic surgery – done alone or in conjunction with chemotherapy or radiation – may offer oropharyngeal cancer patients good outcomes and survival, without significant pain and disfigurement.

Patients with cancers of the base of tongue, tonsils, soft palate and pharynx who underwent TransOral Robotic Surgery, or TORS, as the first line of treatment experienced an average three-year survival from time of diagnosis.

Most notably, the study’s preliminary results reveal oropharyngeal cancer patients who are p16 negative – a marker for the human papilloma virus, or HPV, that affects how well cancer will respond to treatment – have good outcomes with TORS in combination with radiation and/or chemotherapy.

“For non-surgical patients, several studies have shown that p16 positive throat cancers, or HPV- related throat cancers, have better survival and less recurrence than p16 negative throat cancers,” says study lead author Tamer Ghanem, M.D., Ph.D., director of Head and Neck Oncology and Reconstructive Surgery Division in the Department of Otolaryngology-Head & Neck Surgery at Henry Ford Hospital.

“Within our study, patients treated with robotic surgery had excellent results and survival, irrespective of their p16 status.”

Study results will be presented Sunday, Sept. 18 at the 2016 American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) annual meeting in San Diego.

Led by Dr. Ghanem, Henry Ford Hospital in Detroit was among the first in the country to perform TORS using the da Vinci Surgical System. TORS offers patients an option to remove certain head and neck cancer tumors without visible scarring, while preserving speech and the ability to eat.

With TORS, surgeons can access tumors through the mouth using the slender operating arms of the da Vinci, thus not requiring an open skin incision.

Unlike traditional surgical approaches to head and neck cancer that require a large incision and long recovery, TORS patients are able to return to their normal lives only a few days after surgery without significant pain and disfigurement.

For the study, Dr. Ghanem and his colleagues wanted to take a closer look at the effectiveness of TORS for oropharyngeal cancer patients. They reviewed overall three-year survival, cancer control and metastasis, as well as the effect of p16 status on these variables.

The study included 53 Henry Ford oropharyngeal cancer patients who had TORS. Among them, 83 percent were male, 77 percent were Caucasian, and the mean age was 60.8 years. Thirty-seven percent had TORS alone, while more than 11 percent had TORS with radiation therapy, and more than half received chemotherapy and radiation therapy.

Thirty-seven percent had TORS alone, 11.4 percent received radiation therapy, and 50 percent received chemotherapy and radiation therapy. Eighty-one percent of patients had p16+ disease.

The study shows patients with a p16 negative marker had high survival (100 percent) and low cancer recurrence when TORS was the first line of treatment, as well as when TORS was followed by chemotherapy or radiation therapy.

The majority of patients (63 percent) were able to receive a lower dose of radiation after TORS, which reduces the risk of radiation side effects.

While Dr. Ghanem notes the study’s results are not enough to change clinical practice, it does demonstrate that TORS alone or in conjunction with adjuvant radiation or chemotherapy is an acceptable treatment option for oropharyngeal cancer patients regardless of p16 status.

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Why men need to start caring about HPV

Sun, Sep 11, 2016

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Source: www.refinery29.com
Author: Sarah Jacoby

The human papillomavirus (HPV) is one of very few STIs that we have a vaccine for. And — bonus! — that vaccine prevents cancer. But a report from the U.S. Centers for Disease Control and Prevention (CDC) released last month indicated that although we’ve made some improvements in the vaccination rates, they still aren’t where we want them — especially for boys. This is despite the fact that pretty much everyone who’s sexually active will get the virus at some point and men are at risk for their own unique set of HPV-related health consequences.

Let’s start with the basics: “HPV is a virus that’s sexually transmitted, but it’s incredibly common,” explains Kathleen Schmeler, MD, of the University of Texas MD Anderson Cancer Center. Up to 80% of people get it at some point in their lives, she says, which is why some doctors refer to it as the “common cold” of STIs. For most people, the virus goes away on its own, without causing symptoms or needing treatment. Some people develop genital warts that can be treated with medication. But in some rare instances, the virus can go on to cause more serious health issues — including some types of cancer.

“The problem is we don’t know who’s going to clear it and who won’t,” Dr. Schmeler says. Most notably, HPV is known to cause cervical cancer. In fact, nearly all cases of cervical cancer are attributed to HPV. In 2013, the most recent year with available data, almost 12,000 women were diagnosed with cervical cancer in the U.S. and about 4,200 women died from the disease.

In addition to the risks of passing on the virus to their partners, men may face other consequences of HPV. Some types of HPV-related cancer, including throat cancer, are actually more common among men than women. “The rates for that are increasing significantly,” says Dr. Schmeler. “That’s been a huge deal recently.”

However, there is currently no accepted test for HPV-related cancers in men. Women are recommended to get a routine Pap screening, which can detect abnormal cervical cells that may be a result of an HPV infection. But similar screening for anal, penile, and throat cancers in men isn’t recommended.

“The common story that we hear is that [men are] shaving and they find a big lump in their neck,” says Dr. Schmeler. “But by then, it’s advanced disease because it’s spread to the lymph nodes.”

So although Dr. Schmeler’s team is working to find one, there’s no early or precancerous-stage test to detect HPV-related cancer in men.

Because they can’t be tested, it’s that much more important for boys to get the vaccine. Currently, the vaccine is recommended for boys and girls ages 11 to 12 to make sure they get it before they come in contact with the virus. But according to that August report, only about 50% of boys and 63% of girls actually got the vaccine in 2015. While the rates are improving quickly, they’re still nowhere near where they should be.

So why is it that the already-low vaccination rate is even lower for boys than girls? Part of that appears to be due to the way the vaccine was originally marketed: “When it first came out [in 2006], it was recommended only for girls because the primary focus was cervical cancer,” explains Dr. Schmeler. Since then, the CDC has expanded its recommendations to include boys, too. Parents may simply be unaware of the update.

According to research from the CDC, another big problem is that parents don’t believe their kids are (or are about to be) sexually active at that age. Doctors may be reluctant to push the issue or, in some cases, even bring it up.

“Everyone’s so obsessed with the fact that it’s a sexually transmitted disease,” says Dr. Schmeler. “[And in the process, we’re] forgetting that, with this vaccine, we can prevent cancer.”

It may be too late for adult men to get the most out of vaccination — it’s recommended that everyone get the vaccine by age 26. But for it to be it’s most effective, you should ideally get the vaccine before you’re exposed to the virus. And if you’ve already had multiple sexual partners, it’s likely that you’ve already been exposed.

But that doesn’t mean men don’t have to worry about this. In addition to the risk of spreading the virus to their partners, men are at risk for various cancers, as well. The bottom line is that HPV affects everyone, so we should all be equally sharing the burden of stopping the virus — and its associated cancers.

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Chronic sinusitis linked to head and neck cancers in elderly

Sun, Sep 11, 2016

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Source: www.cancernetwork.com
Author: Anna Azvolinsky

Chronic sinusitis is associated with three rare types of head and neck cancer, including nasopharyngeal cancer, human papillomavirus (HPV)-related oropharyngeal cancer, and nasal cavity and paranasal sinus cancers, according to a new study published in JAMA Otolaryngology–Head & Neck Surgery.

Chronic sinusitis is local inflammation caused by either a virus or bacteria that lasts for longer than 12 weeks.

Either the chronic inflammation from the sinusitis, the immunodeficiency that can accompany chronic sinusitis, or both may contribute to the development of these head and neck cancers. The effect is modest, however, wrote the study authors.

“There are currently no general US guidelines for head and neck cancer screening, but given the low absolute risk, our findings do not support a need for head and neck cancer screening in individuals with chronic sinusitis,” wrote study authors Daniel C. Beachler, PhD, MHS, and Eric A. Engels, MD, MPH, of the infections and immunoepidemiology branch of the National Cancer Institute in Bethesda, Maryland.

The absolute risk of these cancer types was low. At 8 years after a chronic sinusitis diagnosis, they had a cumulative incidence of less than 0.07%.

The authors conducted a case-cohort study using the Surveillance, Epidemiology, and End Results (SEER)–Medicare database to assess this link among elderly individuals in the United States.

The authors included 483,546 Medicare beneficiaries and an additional 826,436 individuals from the database who developed cancer, including 21,716 individuals who developed head and neck cancer.

The mean age of individuals in the cohort was 72.6 years and the majority were women (57.7%). About 83% percent of the individuals in the cohort were white.

Among the 483,546 Individuals, those with chronic sinusitis were more likely to be younger, female, white, and to have other upper airway conditions compared with individuals who did not receive a chronic sinusitis diagnosis (P < .001).

Chronic sinusitis was associated with a risk of developing head and neck cancer (adjusted hazard ratio [aHR], 1.37). The risk was highest for nasopharyngeal cancer (aHR, 3.71), HPV-related oropharyngeal cancer (aHR, 1.33), and nasal cavity and paranasal sinus cancer (aHR, 5.49).

This increased risk was weakened over time, the study authors found. Most of the increased risk was limited to within a year of a chronic sinusitis diagnosis. After 1 year or more, the associations decreased (aHRs of 1.60 for nasopharyngeal cancer, 1.07 for HPV–related oropharyngeal cancer, and 2.47 for nasal cavity and paranasal sinus cancer).

Overall, the risk of any cancer type was 8% higher among individuals diagnosed with chronic sinusitis compared to those with no chronic sinusitis (aHR, 1.08).

In an editorial accompanying the study, Elisabeth H. Ference, MD, MPH, and Jeffrey D. Suh, MD, of the department of head and neck surgery at the University of California–Los Angeles, noted that the current study may underestimate the link between chronic sinusitis and cancer risk because the authors analyzed an older age cohort while most inflammatory and infection-related cancers tend to occur at a younger age. “Future studies are necessary to consider whether inflammation in patients with sinusitis contributes to tumorigenesis, especially in middle-aged adults,” concluded the editorial authors.

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Impact of cancer screening in California over past 15 years

Mon, Sep 5, 2016

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Source: www.sciencedaily.com
Author: University of California – Davis Health System

A new report from the UC Davis Institute for Population Health Improvement (IPHI) shows the impact of cancer screening over the past 15 years, identifying areas where increased screening and other cancer-control efforts would save lives and significantly benefit population health.

heatmapThe CalCARES report uses heat maps to show areas with higher proportions of particular cancers diagnosed at a late stage, pointing to a need for increased screening. The CalCARES report uses heat maps to show areas with higher proportions of particular cancers diagnosed at a late stage, pointing to a need for increased screening.

“We have effective screening tests for several cancers, which allow physicians and other health-care providers to identify the disease at an earlier stage — often before symptoms surface — when treatment is more likely to result in a cure,” said senior author of the report and IPHI Director Kenneth W. Kizer. “However, too many Californians are not getting screened and, as a result, many persons are not being diagnosed until their cancers have progressed to an advanced stage.

“With cancer now surpassing heart disease as the leading cause of death in California and 22 other states, we need to increase cancer screening efforts to save lives,” he said.

IPHI’s California Cancer Reporting and Epidemiologic Surveillance (CalCARES) Program works in partnership with the California Department of Public Health to manage the day-to-day operations of the California Cancer Registry (CCR), the state mandated population-based cancer surveillance system. CalCARES researchers routinely review cancer registry data to monitor cancer incidence and mortality trends and identify opportunities to improve cancer-control efforts and reduce the occurrence of cancer.

For their latest report, CalCARES researchers reviewed statewide data from 1999 through 2013 to identify trends in the diagnosis of advanced cancers of the breast, colon and rectum, cervix, prostate, skin, and oral cavity and pharynx — six sites of cancer for which effective screening methods exist. Some of these screening methods include visual inspection or procedures such as mammography, Pap smears, colonoscopy, fecal occult blood tests and prostate-specific antigen testing.

“Showing where in California cancer is being diagnosed after it has spread beyond a localized site shows where lives can be saved through improved screening,” Kizer said.

The report found that in California overall, late-stage diagnoses for cervical, prostate and oropharyngeal cancers significantly increased, but significantly decreased for breast cancer. Diagnosis of late-stage colorectal cancer and melanoma (a form of skin cancer) remained relatively constant. For each of these cancer sites, the researchers calculated important regional and county differences in advanced stage of diagnosis, which takes into account the growth and size of the tumor and whether it has spread to the lymph nodes or other organs.

Trends in advanced cancer diagnoses by cancer type
Cervical cancer: Advanced cancer diagnoses increased statewide, with the highest percentage of late-stage diagnoses in the Central Valley region, followed by the Sacramento and Northern California regions. In the most populated regions of the state, Los Angeles-Orange, San Francisco Bay Area and Scan Diego-Imperial, late-stage diagnoses remained relatively steady. In the San Francisco Bay Area, for example, nearly 50 percent of cases were diagnosed at a late stage in 2013. Only El Dorado county and the High Sierra region saw a significant decrease.

Prostate cancer: Advanced cancer diagnoses increased statewide, especially in Los Angeles-Orange, Central Valley and Sacramento regions, and in Kern, Imperial, Del Norte-Humboldt, Lake and Siskiyou-Trinity counties, where incidence has been persistently high in recent years. Only Napa and Monterey counties saw significantly decreasing percentages of advanced prostate cancer diagnoses in the study period. Since the late 1990s, San Francisco Bay Area has consistently had the lowest percentage of advanced-stage diagnoses for prostate cancer.

Oropharyngeal cancers (cancers of the lip, tongue, floor of mouth, gingiva (gums), mucosa, throat and tonsils): Advanced cancer diagnoses increased in Los Angeles-Orange, San Francisco Bay Area, Central Valley, San Diego-Imperial and Sacramento regions. No counties had decreasing trends.

Female breast cancer: There has been a progression towards early diagnosis of breast cancer statewide, especially in San Francisco Bay Area, Sacramento, San Diego and the High Sierra regions, but pockets of late-stage diagnoses persist in Del Norte-Humboldt and in San Bernardino, Kern, Merced and Kings counties, which had the highest proportion of advanced breast cancers diagnoses in the state.

Colorectal cancers: Advanced cancer diagnoses increased in San Diego-Imperial and Northern California counties, decreased in the San Francisco Bay Area, Inland Empire and Central Valley regions, and remained unchanged and persistently high in Sacramento, Placer, Mendocino, Lake, Lassen-Modoc-Plumas and Santa Cruz counties over time. Counties with worsening trends include Santa Barbara, Sonoma, Butte and Sutter.

Melanoma: Advanced cancer diagnoses decreased in San Francisco Bay Area and Central Coast Counties and increased in Sacramento, the High Sierra and Los Angeles County regions.

IPHI researchers calculated the percent of cases diagnosed at an advanced stage for each cancer type and each county or region by dividing the number of advanced stage cases by the total number of cases for each year. The range of percentages were divided into eight color-coded categories, or heat maps, to indicate a decreasing trend (green tones) an increasing trend (red tones). Counties with fewer than 15 cases were excluded from the county analysis but were included in the regional and state calculations.

Two other recent studies by CalCARES investigators have shown a particularly large need for increased screening for colorectal cancer among Hispanic men in California and a need for greater use of gene expression profile testing for women with early stage breast cancer, especially among women with Medi-Cal health insurance.

Source:
The above post is reprinted from materials provided by University of California – Davis Health System. Note: Content may be edited for style and length.

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Google and UCLH to develop AI to improve cancer therapies

Mon, Sep 5, 2016

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Source: www.phgfoundation.org
Author: Julian Harris

Google’s Artificial Intelligence research group announced a new partnership with University College London Hospitals, applying machine learning to radiotherapy treatment for head and neck cancer.

Abstract, Electronic circuit network grunge background

The new partnership is the third since the launch of DeepMind’s health division in February 2016.

The partnership aims to assist clinicians in the segmentation process – designating which areas of the body to target with radiotherapy – which in the case of head and neck cancer is highly time consuming, taking around four hours. The agreement will give DeepMind access to the anonymised scans of around 700 patients, as well as the expertise of UCLH’s world leading team at their specialised head and neck cancer centre.

Google DeepMind hopes to utilise machine learning to make the planning of radiotherapy treatment more efficient and reduce the duration of the segmentation process. Ultimately , clinicians will still be responsible for deciding on treatment plans, but the reduced workload will free up their time to focus on patient care.

If successful, the team hope that they will be able to adapt their segmentation algorithm to other parts of the body and other cancers which can also be treated with radiotherapy.

Machine learning continues to be a promising new area of health technology, with the potential to provide novel solutions to a range of problems in healthcare. In the UCLH press release, the Co-Founder of DeepMind, Mustafa Suleyman said that “this real-world application of artificial intelligence (AI) technology is exactly why we set up DeepMind… We hope this work could lead to real benefits for cancer patients across the country and for the clinicians who treat them.”

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Expert Asserts Pembrolizumab to Play Important Role in Head and Neck Cancer Treatment

Thu, Sep 1, 2016

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Source: www.targetedonc.com
Author: Laura Panjwani

Joshua-Bauml

The FDA approval of pembrolizumab (Keytruda) as a treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) in August 2016 was extremely significant for this patient population, which previously had limited options following progression on a platinum-based chemotherapy.

The approval was based on the phase Ib KEYNOTE-012 study, which demonstrated that pembrolizumab had an overall response rate (ORR) of 18% and a stable disease rate of 17% in patients with recurrent/metastatic HNSCC.

Several other studies are further evaluating the immunotherapy agent in HNSCC.Preliminary results of the phase II KEYNOTE-055 study—which included 92 evaluable patients who received pembrolizumab after failing platinum and cetuximab therapies—were presented at the 2016 ASCO Annual Meeting.

In an interview with Targeted Oncology, lead study author Joshua M. Bauml, MD, an assistant professor of Medicine, Hospital of the University of Pennsylvania and the Veteran’s Administration Medical Center, discusses the impact of pembrolizumab’s success in HNSCC, the results of the KEYNOTE-055 study, and what he sees on the horizon for the PD-1 inhibitor in this field.

TARGETED ONCOLOGY: What role do you envision pembrolizumab having in this patient population?

Baumi: It is going to play a critical role in head and neck cancer. The other agents that are available have limited efficacy, and are associated with significant toxicities. This is a clear improvement for our patient population with limited options.

TARGETED ONCOLOGY: What were the key takeaways from KEYNOTE-055? Baumi: Patients with recurrent/metastatic head and neck cancer that is refractory to both platinum-based therapy and cetuximab (Erbitux) really have very few options. The historical reference population we usually use is patients treated with methotrexate, which has a response rate of 5% and an overall survival (OS) of only about 6 months. There is a really great need for this. For pembrolizumab, which is an anti–PD-L1 agent, there is biologic rationale to think that it would be active in this patient population. PD-L1 and PD-L2 are unregulated in head and neck cancer.

What KEYNOTE-055 did is really try and create a homogenous patient population. Rather than a large phase I study, here are patients all who have failed both platinum-based therapy and cetuximab. We have really identified the sickest patient population.

What we are able to show in this study was that the drug was well tolerated and it has a response rate of 17% to 18%, which compares favorably for the 5% seen with the prior data with methotrexate. The OS rate was 8 months, which again compares very favorably to the 6 months seen with methotrexate. This was true, even though 85% of patients had received at least 2 prior treatments for head and neck cancer.

TARGETED ONCOLOGY: What did this study tell us about the safety of pembrolizumab in head and neck cancer?

Baumi: The rate of grade 3 through 5 treatment-related adverse events was 12% in our study. Nearly all of the side effects are what you would expect with pembrolizumab; those have been reported in multiple other studies. There was 1 treatment-related death due to pneumonitis, which is a rare side effect of this class of drugs.

Outside of that, it was a really well-tolerated agent. The fact that if you compared grade 3 through 5 toxicities of 12% with cytotoxic chemotherapy, this is a very well-tolerated agent.

TARGETED ONCOLOGY: How common is it for patients to fail both platinum-based therapy and cetuximab?

Baumi: Any patient who has recurrent or metastatic head and neck cancer is going to go through these agents if they survive long enough to get them. Basically, we know that these are the limited tools in our toolbox. We have platinum, we have cetuximab, and then we are really out of options. Many patients have received cetuximab in the locally advanced setting and so we have already lost one of our active treatments. This affects a lot of people.

TARGETED ONCOLOGY: What is next for pembrolizumab in head and neck cancer?

Baumi: There are currently phase III studies evaluating pembrolizumab in head and neck cancer both in combination with and versus traditional cytotoxic chemotherapy to see if we can move up the treatment earlier for patients. The key difference between pembrolizumab and cytotoxics is beyond the improved safety profile. However, we have durable responses; 75% of those patients who responded are still responding to this day. That is really not something that we see.

TARGETED ONCOLOGY: What are the biggest questions that remain regarding the treatment of patients with metastatic head and neck cancer?

Baumi: One of the key questions that relates to immunotherapy—and this covers all tumors—is trying to identify who the 20% of patients are that will respond. Eighty percent of our patients are not responding to our therapies.

Identifying a biomarker to enrich this patient population is very critical. Right now, I would not select patients for pembrolizumab by virtue of PD-L1 status because there were responses in the PD-L1–negative cohorts.

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

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New method of cancer immunotherapy developed

Thu, Aug 25, 2016

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Source: www.nextbigfuture.com
Author: staff

A team of Stanford ChEM-H scientists has discovered a novel form of cancer immunotherapy, which works by removing certain sugars from the surface of cancer cells and making those cells visible to the immune system.

Scientists have long known that if certain sugars are present on a tumor, it is less likely to respond well to therapies. But nobody knew what that halo of sugars was doing, in part because such a small number of labs study the glycocalyx.

Evidence had been mounting within those few labs that do study the glycocalyx, including Bertozzi’s, that a subset of sugars called sialic acids act as a signal for the innate immune system to ignore the otherwise suspicious-looking tumor. Eliminate those sugars, and maybe innate immune cells would be more likely to recognize and attack the cancer cells, Bertozzi thought.

And essentially that’s exactly what happened.

Current immunotherapies on the market work by blocking one of the inhibitory signals that are recognized by the adaptive immune system. Block those and the balance tilts in such a way that the immune system will attack the now recognizable cancer.

Bertozzi’s approach provides a second way of tiling the balance in favor of attack, this time for the innate immune system. She said this study shows just one example of how it could work, but her sugar-removing lawnmower could be used on a wide variety of cell types, not just those expressing HER2, and on different types of sugars.

PNAS – Precision glycocalyx editing as a strategy for cancer immunotherapy

PNAS – Precision glycocalyx editing as a strategy for cancer immunotherapy [Supplemental information]

Significance
Successful tumors are able to evade the immune system, which is otherwise capable of killing transformed cells. Therapies that prevent this evasion have become revolutionary treatments for incurable cancers. One mechanism of evasion is the presentation of sugars, called sialic acids, within the cell surface’s sugar coating, or glycocalyx. Here, we designed biotherapeutic molecules, termed “antibody–enzyme conjugates,” that selectively remove sialic acids from tumor cells. The antibody directs the enzyme to the cancer cells, the enzyme cleaves the sugars, and then the antibody directs immune cells to kill the desialylated cancer cells. The conjugate increased tumor cell killing compared with the antibody alone. Editing the cancer cell glycocalyx with an antibody–enzyme conjugate represents a promising approach to cancer immune therapy.

Abstract
Cell surface sialosides constitute a central axis of immune modulation that is exploited by tumors to evade both innate and adaptive immune destruction. Therapeutic strategies that target tumor-associated sialosides may therefore potentiate antitumor immunity. Here, we report the development of antibody–sialidase conjugates that enhance tumor cell susceptibility to antibody-dependent cell-mediated cytotoxicity (ADCC) by selective desialylation of the tumor cell glycocalyx. We chemically fused a recombinant sialidase to the human epidermal growth factor receptor 2 (HER2)-specific antibody trastuzumab through a C-terminal aldehyde tag. The antibody–sialidase conjugate desialylated tumor cells in a HER2-dependent manner, reduced binding by natural killer (NK) cell inhibitory sialic acid-binding Ig-like lectin (Siglec) receptors, and enhanced binding to the NK-activating receptor natural killer group 2D (NKG2D). Sialidase conjugation to trastuzumab enhanced ADCC against tumor cells expressing moderate levels of HER2, suggesting a therapeutic strategy for cancer patients with lower HER2 levels or inherent trastuzumab resistance. Precision glycocalyx editing with antibody–enzyme conjugates is therefore a promising avenue for cancer immune therapy.

Source:
Stanford University, Proceedings of the National Academy of Sciences of the United States of America
PNAS

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Expert says Nivolumab Poised to Change Standard of Care in SCCHN

Wed, Aug 24, 2016

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Source: www.onclive.com
Author: Laura Panjwani

Robert-Ferris

Nivolumab (Opdivo) is a game-changing agent for the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN), according to Robert L. Ferris, MD, PhD.

“Recent findings have shown us that this agent is really the new standard-of-care option for all platinum-refractory patients with head and neck cancer,” says Ferris, vice chair for Clinical Operations, associate director for Translational Research, and co-leader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute. “This is regardless of whether patients are PD-L1–positive or negative or whether they are HPV-positive or negative.”

The PD-L1 inhibitor received a priority review designation by the FDA in July 2016 based on the CheckMate-141 study, which demonstrated a median overall survival (OS) with nivolumab of 7.5 months compared with 5.1 months with investigator’s choice of therapy (HR, 0.70; 95% CI, 0.51-0.96; P = .0101) in patients with recurrent or metastatic SCCHN.

The objective response rate (ORR) was 13.3% with nivolumab and 5.8% for investigator’s choice. The FDA is scheduled to make a decision on the application for the PD-1 inhibitor by November 11, 2016, as part of the Prescription Drug User Fee Act.

Ferris was the lead author on an analysis that further evaluated preliminary data from CheckMate-141, which was presented at the 2016 ASCO Annual Meeting. In an interview with OncLive, he discusses the findings of this study, potential biomarkers for nivolumab, and questions that remain regarding the use of the immunotherapy in SCCHN.

OncLive: What were the updated findings from CheckMate-141 presented at ASCO?

Ferris: The data that were presented at the 2016 ASCO Annual Meeting were further evaluations and follow-up on some preliminary data—originally presented at the 2016 AACR Annual Meeting—that listed the OS results.

At ASCO, we recapped the primary endpoint of OS as an important endpoint for immunotherapies because response rate and progression-free survival may not be as accurate. Ultimately, the FDA and people at large want OS. In this study, OS was 36% at 1 year in the nivolumab-treated arm and 16.6% in the comparator arm, which was investigator’s choice of single-agent chemotherapy, consisting of methotrexate, docetaxel, or cetuximab. In this phase III randomized trial, nivolumab was given in a 2:1 randomization: 240 patients received nivolumab and 120 received investigator’s choice.

Also at ASCO, we presented further evaluations consisting of what the regimens are in the comparator arm. There was about 20% each of docetaxel and methotrexate and 12% of cetuximab. Approximately 60% of the patients had prior cetuximab exposure and we stratified by cetuximab as a prior therapy. We also demonstrated the ORR, which was 13.3% in the nivolumab-treated arm versus 5.8% in the investigator’s choice arm.

Therefore, there was an improvement in overall response, but the difference seemed more modest than the OS benefit—which was a doubling—with 20% more patients alive at 1 year. This reinforces the concept that perhaps response rate may not be the best endpoint. Progression-free survival (PFS) was double at 6 months, with about 20% in the nivolumab arm versus about 9.9% in the investigator’s choice arm. The median PFS was not different, but the 6-month PFS was twice as high. The time to response was about 2 months in each arm at the first assessment.

Your analysis also looked at biomarkers. Can you discuss these findings and their significance?

The p16 or HPV-positive group had a better hazard ratio for OS than the overall study population. The hazard ratio was .73 for the overall population, using a preplanned interim analysis. With the HPV-positive group, we had a hazard ratio of .55 and the HPV-negative group had a hazard ratio of .99. It is still favoring the nivolumab-treated patients but, with the curves separated earlier in the HPV-positive group, one could see the improvement with nivolumab at about 1 to 2 months. It took 7 or 8 months with the HPV-negative group to show a separation of the curves in favor of nivolumab.

We looked at PD-L1 levels, and PD-L1—using a 1% or above level—had an improvement in the PD-L1–positive patients in favor of nivolumab in terms of OS and ORR. When we looked at 5% and 10% thresholds of PD-L1, the OS did not seem to improve. Therefore, in all levels above 1%, the OS was similarly beneficial over the PD-L1 less-than-1% group. However, essentially all levels of PD-L1–positivity and PD-L1–negativity still favored nivolumab, but the benefit was more when its levels were greater than 1%.

We could combine HPV status with PD-L1 status and look at subsets; however, essentially every subset benefited, whether it was PD-L1–negative or positive. This indicates that, in this group of patients, who progress within 6 months of platinum-based therapy, that no current systemic therapeutic options benefit patients as well as nivolumab.

With regard to these findings, what are you most excited about?

Head and neck cancer is a difficult disease. Until recently, we didn’t know the impact of this enrichment for HPV-positive virus-induced subsets and we didn’t know if this was an immune responsive cancer. Clearly, it is. We have all of the hallmarks that we have seen for a bright future—based on the melanoma data—and a series of other cancers indicating response rates in the 15% to 20% range, suggesting that we now have a platform of the PD-1 pathway to combine with other checkpoints and to integrate earlier in disease with radiation and chemotherapy.

We have a demonstration of head and neck cancer as an immune-responsive cancer. We are beginning to get an idea of the biomarkers and starting to be able to segment patients who will benefit. Now, we have a large comparative trial with an OS endpoint and tissue to look at biomarkers to try and understand what the best future combinations will be.

What are some questions that you still hope to answer regarding nivolumab in head and neck cancer?

We have to get down deeper into the nonresponders. We should acknowledge that the majority of patients neither had a response nor benefited. Understanding who is more likely to benefit is useful, but we also need to understand the levels of alternative checkpoint receptors or other biomarkers of resistance.

We have sequential lymphocyte specimens from the peripheral blood, tissues, and serum so those are intensively under evaluation. There are interferon gamma signatures that have risen from the melanoma checkpoint field that will certainty be applied, as well.

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

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