immunotherapy

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 ligand 1 (PD-L1). PD-L1 is a well-known culprit that cancer and immunosuppressive myeloid cells produce in high amounts to dampen down the immune system.

Led by senior author Clint Allen, Principal Investigator, Section on Translational Tumor Immunology, NIDCD, the team tested the engineered PD-L1 haNKs versus ordinary haNKs against human and mouse head and neck cancer cells. They found that the haNKs expressing the PD-L1 CAR kill mouse and human tumor cells to a greater degree than haNKs without the CAR, and that this ability was retained even if they had already been exposed to cells carrying PD-L1 before. This is important because natural killer cells are known to become ‘exhausted’ after killing target cells.

In mice with head and neck tumors, the haNK cell-based therapy cured the mice in 30% of cases and slowed the growth of tumors in the rest of the mice, without causing toxicity. Treatment with haNKs also reduced the numbers of immunosuppressive myeloid cells that carry PD-L1 within the tumor, while having no effect on other immune-boosting white blood cells.

To investigate whether this effect on the immune cells also occurred in patients, the team incubated white blood cells from people with advanced head and neck cancer with the PD-L1 haNK cells. As they saw in the mice, the immunosuppressive myeloid cells that carry PD-L1 were significantly reduced after treatment with the PD-L1 haNK cells. This suggests that this treatment can both directly kill tumor cells and remove the immunosuppressive myeloid cells that prevent conventional immunotherapies from working.

These findings suggest that haNK cells expressing a PD-L1 CAR may overcome some of the limitations of conventional immunotherapy that relies on T-cell activation, and could be used in patients who are predicted to be insensitive to or have failed existing immunotherapy treatments. The researchers say the next steps would be to take this treatment into the clinic to explore the safety of PD-L1 haNKs in people with advanced or recurring cancer, and to see whether combining haNK cell therapy with other immunotherapies that activate T cells can enhance treatment response.

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 or two prior lines of treatment for metastatic or recurrent disease.

All participants received oral palbociclib (125 mg daily on days 1-21) and IV cetuximab (400 mg/m2 on day 1 of cycle one, followed by 250 mg/m2 once weekly) in 28-day cycles. Objective response, defined as complete and partial responses per RECIST 1.1 criteria, served as the primary endpoint.

Researchers followed patients in group 1 for a median 5.4 months (IQR, 4.4-12.1) and those in group 2 for a median 5.5 months (IQR, 4.3-8.3).

Among 28 evaluable group 1 patients, 11 (39%; 95% CI, 22-59) attained an objective response, including three complete responses. Repeat scans confirmed all but one of the responses. Half of the group 1 patients (n = 14) had stable disease and three (11%) demonstrated progressive disease. Median duration of response was 4 months (IQR, 1.8-5.6), median PFS was 5.4 months (95% CI, 3.4-7) and median OS was 9.5 months (95% CI, 5.3-16.5).

Palbociclib plus cetuximab shows antitumor activity among head and neck cancer subsetAmong 27 evaluable group 2 patients, five (19%; 95% CI, 6-38) achieved an objective response, including one complete response. Four of the responses were later confirmed. Thirteen of the group 2 patients (48%) had stable disease and nine (33%) demonstrated progressive disease. Median duration of response was 6 months (IQR, 2-15.5), median PFS was 3.7 months (95% CI, 2.9-4.3) and median OS was 6.3 months (95% CI, 4.9-10).

In each group, only one patient with a tumor response previously had received immunotherapy.

The most prevalent grade 3 to grade 4 adverse event associated with palbociclib was neutropenia, which occurred in 34% (n = 21) of all patients. The researchers did not document any treatment-related deaths.

The researchers cited various limitations to their study, including its single-group design, and noted that the results will need to be confirmed in a controlled trial with a larger sample size. They acknowledged that immunotherapy might have affected OS outcomes, and that the study design did not permit the evaluation of whether palbocilib’s antitumor activity occurred directly or by reversal of primary cetuximab resistance.

These data suggest a need for further study of palbociclib in patients with recurring or metastatic HNSCC, according to a related editorial by Garth W. Strohbehn, MD, hematology/oncology fellow at University of Chicago, and Everett E. Vokes, MD, professor of medicine and radiation oncology physician-in-chief at University of Chicago Medicine.

“However, we should be circumspect about the prospect of CDK 4/6 inhibitors as standardized, cost-effective therapies in recurrent and metastatic HNSCC,” the authors wrote. “Bringing this class of drugs to head and neck oncology clinics, as either monotherapies or immunotherapy partners, will require appropriately controlled studies linked to biomarker evaluation with both survival and cost-effectiveness endpoints.” – by Jennifer Byrne

Source:
Adkins D, et al. Lancet Oncol. 2019;doi:10.1016/S1470-2045(19)30405-X.
Strohbehn GW and Vokes EE. Lancet Oncol. 2019;doi:10.1016/S1470-2045(19)30484-X.

Disclosures: Adkins reports research funding from Pfizer as part of the work presented in the study; personal fees for advisory/consultant roles from Celgene, Cue Biopharma, Eli Lilly, Loxo Oncology, Merck and Pfizer; and research funding from AstraZeneca, Atara, Blueprint Medicine, Bristol-Myers Squibb, Celgene, CellCeutix, Celldex, Eli Lilly, Enzychem, Exelixis, Gliknik, Kura, Matrix Biomed, Medimmune Innate, Novartis, Pfizer and Polaris outside the submitted work. Please see the study for all other authors’ relevant financial disclosures. Vokes reports consultant/advisory roles with AbbVie, Amgen, AstraZeneca, Bristol-Myers, Celgene, EMD Serono, Genentech, Merck, Novartis and Regeneron. Strohbehn reports no relevant financial disclosures.

August, 2019|Oral Cancer News|

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 industry’s immuno-oncology leader with sales expected to top $10 billion this year and $20 billion in 2024, according to IBES data from Refinitiv.

Keytruda brought in revenue of $7.17 billion for Merck in 2018, while Bristol’s Opdivo earned $6.74 billion.

June, 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
May, 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 from the analysis.

“Although the effect for some individual cancers did not reach statistical significance, possibly because of smaller sample size, the numerical trend of better overall survival was observed in nearly all cancer types, with glioma the clearest exception,” the authors wrote. These findings mirror real-world evidence, which has shown gliomas to be immunosuppressive and remain difficult to treat.

Of note, what constituted as high tumor mutational burden varied greatly by cancer type, which suggests that there is likely not a viable universal number that could define high tumor mutational burden and be predictive of response to immune checkpoint inhibitors across all cancers. While breast cancers and renal cell carcinomas only need 6 mutations per 1 million DNA to predictably respond well to immune checkpoint inhibitors, melanomas need 30.7 and colorectal cancers need 52.2.

According to the researchers, this can likely be explained by distinct tumor microenvironments as well as other factors that have shown to independently predict response, including clonality, immune infiltration, and immune cell exclusion.

Reference:

Samstein R, Lee C, Shoushtari A, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types [publihsed online January 14, 2019]. Nature. doi: 10.1038/s41588-018-0312-8.

January, 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 the 20% of cancers in their data with the most mutations, these people responded better to ICI than those with lower numbers of mutations in their tumors.

However, this correlation did not hold true for all tumors, for example, in people with a type of brain cancer called glioma, those with TMB in the top 20% did no better on ICI than those with lower TMB. Also in breast cancer there was no conclusive evidence that a higher TMB predicted response to ICI, although the study included relatively few breast cancer patients as ICI is not currently widely used for the disease.

Researchers don’t exactly know why high numbers of mutations make cancers more susceptible to immunotherapy, but they do have a very plausible theory. They think that the more mutated a cell is, the more likely it is to produce incorrect, mangled proteins. These displayed on the cell surface are called neoantigens and they are so far from what would be considered normal, the immune system identifies them as foreign and attacks the cells.

This is not a unique study in concept, with previous research on a smaller number of cancers of specific types, notably lung and melanoma, indicating that TMB is likely predictive of immunotherapy response. However, it is the largest and most comprehensive study to date, providing the most persuasive evidence that this is true for a greater number of cancer types.

“Only in lung cancer is TMB being used in a clinical trial. Hopefully this data will give us permission to include it in future clinical trials on other cancer types,” said Morris.

However, some patients with high TMB don’t respond to ICI at all, so there is still work to be done to figure out why high TMB is not a universal predictor of response to ICI.

“TMB by itself is not going to give you a high confidence in predicting whether a patient is going to respond to immunotherapy or not. It is one biomarker for response, but a number of other factors are important. I would not suggest you take the data from this paper and apply it to a patient in the clinic,” said Morris.

January, 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 do it accurately.

The liquid biopsy industry has exploded in 2018, perhaps unsurprising given the market is expected to be worth over $2 billion annually by 2022. The promise is that eventually, we should be able to diagnose cancer with a simple blood test, earlier, more cheaply and even more accurately than we currently do and even use these tests to monitor response to cancer treatment and when and if a tumor returns.  As a cancer research scientist, the number of research papers, presentations at top conferences and news releases by the dozens of companies currently developing these technologies can make it a little overwhelming to figure out what is going on.

In 2018, two of the top liquid biopsy tests on the market had their efficacy called into question with researchers from Johns Hopkins suggesting that the two competing tests gave different results with the same patient samples. A claim which was then challenged by representatives from both companies.

Liquid biopsy tests undoubtedly have huge potential and may indeed live up to their hype, but currently, the field is a little messy and difficult to understand for scientists, patients and oncologists who are not specialists. The American Society for Clinical Oncology (ASCO) issued a statement in March of this year essentially concluding that for most liquid biopsy tests there is currently not enough evidence to recommend their use in either the diagnosis or monitoring of cancer. Hopefully, 2019 brings greater clarity about how these tests can fit into the diagnosis and care of people with cancer and ASCO will be able to review their stance accordingly.

3. More focus on the side-effects of cancer treatment.

As a cancer survivor myself and an advocate for more research into what happens to cancer survivors past the ‘all clear,’ 2018 has been a remarkable year for research into the numerous and often disabling side-effects cancer survivors experience. For decades, cancer research has understandably been mainly focused on making sure as many people survive the disease as possible, but now with millions of cancer survivors in the world, a new research field looking at what actually happens to cancer survivors as a result of their treatments is growing at considerable speed.

From a study which hopes to have found a solution to male infertility after childhood cancer treatment to work showing that some women with early-stage breast cancer can have less radiotherapy without compromising their chance of survival, 2018 was a good year for cancer survivorship research. The highlight, in my opinion, was work from Stanford University scientists that may have figured out why ‘chemo brain’ happens, one of the most commonly-reported side-effects that cancer survivors experience. Even better, the scientists suggest that it may be treatable.

4. Cancer and the microbiome.

The microbiome has been one of the most talked about topics in medicine in 2018 and shows no sign of slowing down. Amidst the predictable flurry of supplements, fad-diets and blog posts giving scientifically-questionable advice telling you how to cherish and nurture your own gut flora, plenty of solid, evidence-backed research has been published showing that the microbiome is potentially involved in multiple sclerosis, inflammatory bowel disease and even Alzheimer’s disease. But what about cancer?

There are already several studies published showing that the microbiome can influence the response to chemotherapy drugs and even in some cases cause the production of toxic breakdown products of the drug. Earlier this month, work published in Nature Communications showed how a particular bacterial strain common in the human microbiome could influence the immune system to drive the progression of a currently incurable type of blood cancer called multiple myeloma. The study raised the possibility that targeting these bacteria with drugs could halt or slow the disease.

5. Organoids, the new secret weapon in personalized cancer medicine.

Back in November 2017, I wrote about how organoids, tiny lab-grown organs made from patient tissue samples would revolutionize the treatment of cancer by allowing researchers to test drugs on patient tumors before deciding which to give the patient. Several pharmaceutical and biotechnology companies have large-scale programs to commercially develop these technologies for using organoids in drug screening for patients and the increasing accessibility of organoid growing kits from companies which supply academic and hospital research laboratories mean research papers are coming out thick and fast.

But, organoids are by no means a perfect way to test new drugs yet. For example, it is easy and quick to make organoids from certain tumor types-such as colorectal, but very difficult from others such as brain tumors. Organoids grown in the lab also don’t have a blood supply, nor are they connected to other body systems which may influence the response of a patient to anti-cancer drugs. But researchers are making progress in organoid development all of the time, figuring out better ways to make and culture them so they more accurately reflect the tumor they were originally made from.  Expect to see them playing an increasing role in designing personalized medicine approaches for cancer patients as well as being involved in more lab-based cancer breakthroughs.

January, 2019|Oral Cancer News|

Hospitals required to post all prices online beginning January 1

Date: 12/26/18
Source: KATV
Author: Associated Press

 

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 the Trump administration has invited technology companies to design secure apps that would let patients access their records from all their providers instead of having to go to different portals.

Verma also announced Medicare is starting a comprehensive review of how it will pay for a costly new form of immunotherapy called CAR-T. It’s gene therapy that turbocharges a patient’s own immune system cells to attack cancer.

Immune system T cells are filtered from the patient’s own blood and reprogrammed to target and kill cancer cells that had managed to evade them. Hundreds of millions of copies of the revved-up cells are then returned to the patient’s blood to take on the cancer.

Though only a couple of such treatments have been approved for blood cancers, the cost can exceed $370,000 per patient.

“It’s a new area for the agency,” said Verma. “We haven’t seen drugs priced at this level and we’re having to think about our strategy.”

January, 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 advanced head and neck cancer overall, and in a group of patients has really dramatic benefits. It is also a much kinder treatment than those currently approved,” said Professor Kevin Harrington, professor of Biological Cancer Therapies at The Institute of Cancer Research, London, and consultant at The Royal Marsden NHS Foundation Trust.

“I would like to see pembrolizumab approved for use in the clinic, so that people with advanced head and neck cancer can be offered the chance of a longer life and improved quality of life.

“There is also an urgent need to work out how we can identify in advance which patients are likely to benefit, given that some of these people may do much better than they do on standard treatment.”

The trial was sponsored and funded by MSD, and the results are published in The Lancet.

December, 2018|Oral Cancer News|

Study: Immunotherapy better than chemotherapy for subtype of head and neck cancer

Date: November 30th, 2018
Source: Scienmag

A randomized clinical trial involving 97 medical centers in 20 countries, including Moores Cancer Center at UC San Diego Health, found that treating patients who have chemotherapy-resistant head and neck cancer with the immunotherapy drug pembrolizumab is more effective and less toxic than standard chemotherapy, reports an international team of researchers in the November 30 online issue of The Lancet.

Previous research had shown that pembrolizumab (Keytruda) was safe and effective for treating patients with recurrent or metastatic head and neck squamous cell carcinoma whose disease had progressed while on or after receiving standard chemotherapy. Data from this clinical trial called KEYNOTE-040, a phase III study sponsored by Merck & Co., the manufacturer of the drug, takes the research a step further by comparing the immunotherapy drug head-to-head to three go-to chemotherapy drugs currently used as standard treatment: methotrexate, docetaxel and cetuximab.

“We compared pembrolizumab against standard of care to see if it fulfilled the promise of early data for patients who are unlikely to do well on standard therapy,” said Ezra Cohen, MD, professor of medicine at University of California San Diego School of Medicine and corresponding author on the study.

“In this trial, patients who received pembrolizumab alone had a higher response rate compared to those receiving standard chemotherapy while those responses lasted, on average, one-and-a-half years. Furthermore, the median survival at one year was markedly better. I feel it is safe to say that these types of therapies should be the new standard therapy for people with cancer that recurs and is resistant to therapy.”

Pembrolizumab is an antibody that inhibits the abnormal interaction between the molecule PD-1 on immune cells and the molecule PD-L1 on tumor cells, allowing the immune cells to activate and attack tumors. Similar results were recently published for another anti-PD-1 drug, nivolumab (Opdivo). Both drugs should be considered by treating physicians for patients with this disease, said Cohen.

The study also pointed to potential biomarkers that can guide oncologists to determine which patients are most likely to respond to these anti-PD-1 drugs.

“It’s fairly clear that patients whose tumors express PD-L1 are most likely to benefit from this type of immunotherapy drug,” said Cohen, associate director for translational science at Moores Cancer Center and an internationally recognized physician-scientist who specializes in novel cancer therapies. “In this trial, overall survival was driven by PD-L1 expression. Only patients whose tumors expressed PD-L1 had a response to pembrolizumab and those responses tended to be durable.”

Over a 17-month period, 247 patients were randomized to receive pembrolizumab and 248 patients were randomly selected by their physicians to receive one of the three standard therapies. The median overall survival for patients receiving immunotherapy was 8.4 months and 6.9 months for patients treated with standard care. Patients received treatment until their cancer progressed, they developed unacceptable toxicity, they withdrew or their physician removed them.

The median duration of response was 18.4 months in the pembrolizumab group, compared with five months in the standard therapy group.

Twelve months after initiating the trial, 37 percent of patients receiving pembrolizumab were alive compared to 26.5 percent of patients on standard therapy.

###

Co-authors include: Denis Soulières, Centre Hospitalier de l’Université de Montréal; Christophe Le Tourneau, Institut Curie, INSERM U900 Research Unit, Versailles-Saint-Quentinen-Yvelines University; José Dinis, Instituto Português de Oncologia do Porto Francisco Gentil; Lisa Licitra, Fondazione IRCCS Istituto Nazionale dei Tumori; Myung-Ju Ahn, Samsung Medical Centre; Ainara Soria, Hospital Universitario Ramón y Cajal; Jean-Pascal Machiels, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain; Nicolas Mach, Hôpitaux Universitaires de Genève; Ranee Mehra, Fox Chase Cancer Center; Barbara Burtness, Yale University School of Medicine and Yale Cancer Center; Pingye Zhang, Jonathan Cheng, Ramona F Swaby, Merck & Co; and Kevin J Harrington, The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust, National Institute of Health Research Biomedical Research Centre.

This research was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co. The funder contributed to study design, data collection, data analysis, data interpretation, and the writing of The Lancet paper. The funder maintained the study database. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Disclosure: Cohen reports grant support to the institution from Merck Sharp & Dohme for clinical research related to the submitted work and serving an advisory role for AstraZeneca, Bristol-Myers Squibb, Eisai, Merck, Human Longevity and Pfizer, all outside the submitted work.

December, 2018|Oral Cancer News|