Why immunotherapy only works for some with head and neck cancer

Source: medicalxpress.com Author: Katie Pence, University of Cincinnati Image of a healthy T cell on left compared to a cancer T cell on right. Credit: Ameet Chimote University of Cincinnati researchers have discovered new clues into why some people with head and neck cancer respond to immunotherapy, while others don't. Findings published in the Journal for ImmunoTherapy of Cancer show that it could all come down to "channeling" the power and function within one particular type of immune cell. Laura Conforti, Ph.D., professor in the Department of Internal Medicine at the UC College of Medicine and corresponding author on the study, says understanding these mechanisms could help in creating combination treatments to more effectively treat some patients with cancer. She points out that head and neck cancers are the sixth most common cancers in the world, affecting about 53,000 Americans every year. To combat the deadly disease, doctors often turn to immunotherapy, which boosts the body's own immune system in an effort to identify and kill cancer cells. "Our immune cells are naturally programmed to distinguish between our body's 'normal' cells and what they see as 'foreign' cells and attack only the foreign cells," explains Conforti. She says the immune cells—called T cells— lead the body's attack against cancers but the impact of that attack can be proven futile if a molecule in cancer cells is able to bind to an immune checkpoint in the T cells and effectively "turn them off like a light switch." As a [...]

2020-11-25T13:38:19-07:00November, 2020|Oral Cancer News|

Engineered killer immune cells target tumours and their immunosuppressive allies

Source: medicalxpress.com Author: eLife staff Scientists have engineered natural killer immune cells that not only kill head and neck tumor cells in mice but also reduce the immune-suppressing myeloid cells that allow tumors to evade the immune response, according to a new study in eLife. The engineered cell therapy could be used as an alternative approach for treating cancer in patients for whom previous immunotherapy based on the activation of T cells has failed. These findings are reported by researchers at the U.S. National Institutes of Health (NIH) in Bethesda, Maryland. In recent years, treatments called T-cell therapy or CAR-T cell therapy have been approved to treat blood cancers, and many others are now in development for other forms of cancer. However, these T-cell therapies rely on the ability to reprogram a patient's own T cells to express a chimeric antigen receptor (CAR) that targets tumor cells. This process of reprogramming a patient's own T cells is expensive and laborious. High affinity natural killer cells (haNKs) represent potential 'off-the-shelf' cell therapies that do not rely on reprogramming a patient's own immune cells. The same cells could be produced in mass and potentially given to anyone. But the presence of immune-suppressing myeloid cells in the tumor microenvironment remains a barrier to effective immunotherapy, including haNK cell-based treatment. To address this barrier, researchers from the NIH's National Institute on Deafness and Other Communication Disorders (NIDCD) and National Cancer Institute have utilized haNKs expressing a CAR that targets a molecule called programmed death [...]

Palbociclib plus cetuximab shows antitumor activity among head and neck cancer subset

Source: www.healio.com Author: Adkins D, et al. A combination of palbociclib and cetuximab demonstrated substantial antitumor activity among patients with platinum- or cetuximab-resistant HPV-unrelated head and neck squamous cell carcinoma, according to results of a multigroup phase 2 trial published in The Lancet Oncology. “Currently, effective therapeutic options for patients with cetuximab-resistant HNSCC are few. Traditional chemotherapy has marginal activity, with 6% of patients or fewer achieving a tumor response,” Douglas R. Adkins, MD, professor in the oncology division of the department of medicine at Washington University School of Medicine in St. Louis, and colleagues wrote. “The most effective therapy for these patients might be pembrolizumab [Keytruda, Merck] or nivolumab [Opdivo, Bristol-Myers Squibb], which have resulted in responses in 11% to 16% of patients and median OS of 6.9 months to 8 months. Novel treatment strategies are needed for patients with recurrent or metastatic HNSCC.” The combination of the cyclin-dependent kinase (CDK) 4/6 inhibitor palbociclib (Ibrance, Pfizer) and epidermal growth factor receptor inhibitor cetuximab (Erbitux, Eli Lilly) appeared safe and tolerable in the phase 1 portion of the multicenter trial, conducted across eight U.S. university sites. For phase 2, Adkins and colleagues divided 62 patients with HPV-unrelated HNSCC (median age, 66 years; interquartile range [IQR], 58-70; 71% men) into two groups: those who were platinum-resistant (group 1; n = 30) and those who were resistant to cetuximab (group 2; n = 32). Primary tumor sites included the oral cavity (42%) and larynx (29%), and 81% of patients had received one [...]

Merck’s Keytruda wins FDA approval to treat head and neck cancer

Source: Reuters Date: June 11, 2019 Author: Reporting by Aakash Jagadeesh Babu; Editing by Shailesh Kuber (Reuters) - Merck & Co Inc said on Tuesday its blockbuster cancer drug Keytruda won approval from the U.S. Food and Drug Administration to treat a type of head and neck cancer. The drug was approved for use as a monotherapy, as well as in combination with a common chemotherapy regimen, to treat previously untreated patients with head and neck squamous cell carcinoma, Merck said. The approval is based on results from a late-stage trial, where Keytruda showed a significant improvement in overall survival in cancer patients, Merck said. Keytruda, a type of immunotherapy called a PD-1 inhibitor, is already an approved treatment for several forms of cancer, including lung and skin cancers. Head and neck cancer includes tumors in the mouth, tongue, nose, sinuses, throat and lymph nodes in the neck. Merck estimates that there will be more than 65,000 new cases of head and neck cancer diagnosed in 2019 in the United States. Keytruda works by increasing the ability of patients’ immune system to help detect and fight tumor cells. The drug has been amassing approvals as a standalone therapy and in combination with other drugs to treat several forms of cancer. It is the leading immunotherapy for treating lung cancer, ahead of rival drugs from Bristol-Myers Squibb, Roche and AstraZeneca. Keytruda, first approved for advanced melanoma in 2014, is Merck’s most important growth driver. It has overtaken Bristol’s Opdivo as the [...]

2019-06-12T09:48:16-07:00June, 2019|Oral Cancer News|

Queensland scientist develops new HPV cancer vaccine

Source: 9News Date: May 22, 2019 Author: 9News Staff *click Source to view video* Former Australian of the Year Professor Ian Frazer has developed a vaccine aimed at treating HPV-related cancers of the head, neck, throat and tongue. While funding is still being finalised, a trial of the vaccine is being prepared for people with incurable oropharyngeal cancers. Professor Frazer, the Scottish-born immunologist who developed and patented the vaccine against HPV-related cervical cancer, has been working on this vaccine for nearly 15 years. While the cervical cancer vaccine works as a preventative, this new vaccine is a treatment therapy. It works by teaching the patient’s immune system to target the cancer cells containing HPV. The patient will then be given immunotherapy drugs that supercharge the immune system. “This is all about a new way to treat cancer using the body's defence against infection,” Professor Frazer said. “This might give a second chance at life.” HPV-related throat cancer kills three Australians every day. “It's going to become a major problem in Australia, in fact in the US we've seen an increase in HPV-related throat cancers by 225 per cent," head and neck radiation oncologist Sandro Porceddu said. Professor Porceddu will conduct the trial at the Princess Alexandra Hospital. It should begin towards the end of this year if a further $700,000 in necessary funding is found. © Nine Digital Pty Ltd 2019

2019-05-22T16:06:08-07:00May, 2019|Oral Cancer News|

Tumor Mutational Burden Predicts Who Will Respond to Immunotherapy

The advent of immunotherapy has significantly shifted the treatment paradigm and prognosis for multiple advanced-stage cancers. In cancers like metastatic melanoma and non–small cell lung cancer (NSCLC), the treatment class has greatly improved survival rates. However, not all patients respond to the treatments, highlighting the need for predictive biomarkers to determine which patients will benefit. Early reports and small cohorts have suggested high tumor mutational burden being associated with improved clinical response, and now a large study has confirmed the hypothesis. “Given the potential toxicities of immunotherapy and the highly variable response to immune checkpoint inhibitors, as well as the significant economic cost of these agents, there is an urgent need for biomarkers that can predict immunotherapy response,” explained the researchers of the study. Looking at data from more than 1000 patients with stage IV or metastatic disease for which immune checkpoint inhibitors are approved, including NSCLC, melanoma, renal cell carcinoma, bladder cancer, and head and neck cancer, researchers found that higher somatic tumor mutational burden is associated with improved overall survival. Patients were treated with atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab, pembrolizumab, or tremelimumab. Tumor mutational burden was calculated by normalizing the number of somatic nonsynonymous mutations to the total number of megabases sequenced, and noting that mutational load varies across tumor types, the researchers defined tumor mutational burden within each cancer type. The authors found that, across all cancers, more mutations translated into improved overall survival. The authors noted that the association remained even when removing NSCLC and melanoma [...]

2019-01-22T11:03:57-07:00January, 2019|Oral Cancer News|

Researchers Uncover Major Clue In Predicting Response To Immunotherapy

Researchers at Memorial Sloan Kettering Cancer Center in New York have discovered that cancer cells with high numbers of faults in their DNA are more likely to respond to immune checkpoint inhibitors (ICI), a major class of immunotherapy drugs, which includes Keytruda. The study, published today in Nature Genetics adds important pieces to the puzzle as to why some cancer patients respond to immunotherapy whereas others do not. The researchers measured 'tumor mutation burden (TMB)', essentially counting how many DNA faults a tumor contains by looking for errors in the DNA sequence. "People assume that TMB is important in predicting response to immunotherapy in all cancers, but up until now, all we've had is data from small studies and clinical trials on mostly lung cancers and melanoma," said Luc Morris, MD, surgical oncologist at Memorial Sloan Kettering Cancer Center and one of the lead authors of the paper. The researchers studied the DNA of 1,662 patients with advanced cancer (classified as stage IV or metastatic disease) treated with one or more of several FDA-approved ICI drugs and DNA from 5,371 patients with advanced cancer who had not had ICI. They used a tool called MSK-IMPACT, which looks at just 3% of the coding-regions in DNA, but is correlated to the number of mutations in the genome. "Is TMB associated with likelihood that immunotherapy has benefit? Is this true in all cancers? We wanted to find out whether TMB had broad applicability," said Morris. The researchers found that if they took [...]

2019-01-16T11:03:13-07:00January, 2019|Oral Cancer News|

Five Things To Look Out For In Cancer Research In 2019

Date: 12/28/18 Source: Forbes.com Author: Victoria Forster 2018 was a remarkable year for cancer research, with great strides made in diagnosing and treating various types of cancer as well as important breakthroughs looking at the health of cancer survivors. What can we expect to see from cancer research in 2019? As a cancer research scientist, here are the top five topics that I'll be looking out for. 1. Immunotherapy. Who will respond, who won't respond and why? Immunotherapy is now seemingly everywhere, with several therapies approved for various cancer types, including CAR T-cells and immune checkpoint inhibitors and several more in development such as tumor infiltrating lymphocyte (TIL) therapy. TILs successfully cleared all tumors from a woman with metastatic breast cancer, in a research breakthrough which was one of the most reported in 2018. Over 2,500 trials are now registered worldwide, but as the use of immunotherapy grows, there are still major questions to be answered. One particularly important to the use of immune-checkpoint blocking drugs such as those which target PD-1 or CTLA-4 is 'why do some patients respond whereas others do not?' Several research teams worldwide are currently grappling with this question, which is unlikely to have a single, clear answer, but I expect to see much more research published on this in 2019, which will hopefully start to benefit patients by identifying who will and won't respond to these expensive drugs. 2. Liquid biopsy tests. More clarity on precisely what they do and more evidence that they [...]

2019-01-02T13:07:21-07:00January, 2019|Oral Cancer News|

Hospitals required to post all prices online beginning January 1

Date: 12/26/18 Source: KATV Author: Associated Press   WASHINGTON (AP) — Medicare will require hospitals to post their standard prices online and make electronic medical records more readily available to patients, officials said Tuesday. The program is also starting a comprehensive review of how it will pay for costly new forms of immunotherapy to battle cancer. Seema Verma, head of the Centers for Medicare and Medicaid Services, said the new requirement for online prices reflects the Trump administration’s ongoing efforts to encourage patients to become better-educated decision makers in their own care. “We are just beginning on price transparency,” said Verma. “We know that hospitals have this information and we’re asking them to post what they have online.” Hospitals are required to disclose prices publicly, but the latest change would put that information online in machine-readable format that can be easily processed by computers. It may still prove to be confusing to consumers, since standard rates are like list prices and don’t reflect what insurers and government programs pay. Patients concerned about their potential out-of-pocket costs from a hospitalization would still be advised to consult with their insurer. Most insurance plans nowadays have an annual limit on how much patients must pay in copays and deductibles — although traditional Medicare does not. Likewise, many health care providers already make computerized records available to patients, but starting in 2021 Medicare would base part of a hospital’s payments on how good a job they do. Using electronic medical records remains a cumbersome task, and [...]

2019-01-02T12:52:16-07:00January, 2019|Oral Cancer News|

Immunotherapy extends the life of head and neck cancer patients

Source: Pharmatimes.com Date: 12/3/18 Author: Anna Smith A new immunotherapy can greatly extend the lives of a proportion of people with advanced head and neck cancer, with some living for three years or more, reports a major new clinical trial. The study, by The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, found that the drug – MSD’s Keytruda (pembrolizumab) - has been shown to have significant benefits for patients, with 37% of those who received it surviving for a year or more, compared with only 26.5% of those on standard care. The drug was evaluated in a trial of nearly 500 patients with very advanced head and neck cancer that had spread around the body and already become resistant to platinum chemotherapy, the first-line treatment for the disease. Some 247 patients were randomised to receive Keytruda and 248 to standard of care – chemotherapy or the targeted agent Erbitux (cetuximab). When chemotherapy or targeted therapies stop working, treatment options for people with advanced head and neck cancer are limited, and they are normally expected to survive for less than six months. Patients in the Keytruda arm survived for a median of 8.4 months, compared to 6.9 months with standard treatment. However, a minority of patients responded extremely well to Keytruda – 36 patients saw their cancer partially or completely disappear, and some are still cancer free three years after first receiving the drug. “Our findings show that the immunotherapy pembrolizumab extends the life of people with [...]

2018-12-05T17:20:46-07:00December, 2018|Oral Cancer News|
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