For some patients who are newly diagnosed with metastatic lung cancer, the combination of a treatment that helps the immune system to fight cancer—an immunotherapy—and chemotherapy may help them to live longer than chemotherapy alone, according to the results of a large clinical trial.
After a median follow up of 10.5 months, patients who received pembrolizumab were 51% less likely to die than patients who received chemotherapy alone. After 12 months, an estimated 69.2% of patients in the pembrolizumab–chemotherapy combination group, but only 49.4% of those in the chemotherapy group, were still alive.
Pembrolizumab is one of a class of immunotherapy drugs known as checkpoint inhibitors.
The results, from the KEYNOTE-189 clinical trial, were presented at the annual meeting of the American Association for Cancer Research (AACR) in Chicago on April 16 and published concurrently in the New England Journal of Medicine.
Last year, the Food and Drug Administration (FDA) approved the combination of pembrolizumab and chemotherapy for some patients with NSCLC. But the treatment has not been widely adopted, in part because the trial that led to its approval was a small phase 2 study, said Roy Herbst, M.D., Ph.D., of the Yale Cancer Center.
Clinicians have been waiting for the results of the phase 3 trial, noted Dr. Herbst, who discussed the KEYNOTE-189 trial during a plenary session at the AACR meeting. “And these results have exceeded all expectations.”
He and other experts at the meeting predicted that the pembrolizumab–chemotherapy combination would now be commonly used as the initial treatment for certain patients.
“This study represents a total change in the way we approach the treatment of patients with metastatic lung cancer,” said the trial’s lead investigator, Leena Gandhi, M.D., Ph.D., of the Perlmutter Cancer Center at NYU Langone Health.
A New Treatment Option
In the clinical trial, more than 600 patients were randomly assigned to receive either a standard chemotherapy regimen alone or the chemotherapy regimen plus pembrolizumab—both as an initial treatment for 3 months and as an extended, or maintenance, treatment.
Patients were eligible for the trial if they had not been treated previously for advanced lung cancer and if their tumors lacked mutations in the ALK or EGFR genes. (Effective targeted therapies exist and are the standard of care for patients whose tumors have ALK or EGFR mutations.)
Merck, which manufactures pembrolizumab, funded the trial.
After a median follow-up of 10.5 months, the estimated median overall survival was 11.3 months in the chemotherapy-alone group but was not reached in the pembrolizumab-combination group.
Patients in the trial treated with pembrolizumab also lived longer without their disease progressing, with a median progression-free survival of 8.8 months versus 4.9 months in patients treated only with chemotherapy.
The addition of the immunotherapy drug to chemotherapy did not substantially increase side effects, Dr. Gandhi noted. However, more patients receiving pembrolizumab experienced a sudden change in kidney function, a condition known as acute kidney injury (5.2% in the pembrolizumab-combination group versus 0.5% in the chemotherapy-alone group).
Patients receiving the combination therapy—and especially patients who may be at risk for kidney problems—should be monitored closely for side effects, noted Arun Rajan, M.D., who studies lung cancer in NCI’s Center for Cancer Research and was not involved in the study.
Testing a Combination of Immunotherapy Drugs
“This is a new era for non-small cell lung cancer,” Dr. Herbst said. The new results, he went on, build on decades of advances in treating lung cancer that began with chemotherapy, continued with targeted therapies, and have led, most recently, to immunotherapies.
But, despite this progress, many patients with metastatic lung cancer who initially respond to these treatments experience a recurrence, Dr. Herbst continued. “We’re doing well, but we can do even better by personalizing therapies.”
He noted that another clinical trial presented at the meeting (and published in the New England Journal of Medicine) could help move the field in this direction by providing information about a potential biomarker of response to immunotherapy called tumor mutational burden. This measurement is an assessment of the number of genetic mutations in a tumor.
Of the 1,004 patients for whom information on tumor mutational burden was available, 444 were found to have a high mutational burden. Among this group, the estimated 1-year progression-free survival rate was 42.6% with nivolumab plus ipilimumab versus 13.2% with chemotherapy. After a minimum follow-up of 11.5 months, patients who received the immunotherapy combination were 42% less likely to have their cancer progress or to die than those in the chemotherapy group.
Among patients with a low tumor mutational burden, progression-free survival was similar between the combination-immunotherapy group and the chemotherapy group. The rates of treatment-related side effects were similar between the two groups.
Matthew Hellmann, M.D., of Memorial Sloan Kettering Cancer Center presented results from the study, which was supported by Bristol-Myers Squibb and Ono Pharmaceutical, in Chicago.
Although longer follow-up is needed to assess whether combination immunotherapy extends overall survival compared with chemotherapy, Dr. Rajan said the ipilimumab–nivolumab combination “could be a potential treatment option for patients with NSCLC who have high tumor mutational burden, lack targetable genomic changes, and wish to avoid chemotherapy altogether.”
Identifying New Molecular Subtypes of Lung Cancer
“This study builds on the progress we’ve made in precision medicine for lung cancer and validates tumor mutational burden as a biomarker,” said Dr. Hellman.
Both studies collected information on a different biomarker of potential response to checkpoint inhibitors—the levels of a protein called PD-L1 on tumor cells.
In CheckMate-227, patients with high tumor mutational burden benefited from the combination of nivolumab and ipilimumab regardless of PD-L1 level. In KEYNOTE-189, patients with high and low PD-L1 levels benefited from the pembrolizumab combination, “but there was increasing benefit with increasing levels of PD-L1,” said Dr. Gandhi.
She stressed the importance of learning more about how to “differentiate patients” and predict responses to immunotherapies. “PD-L1 could be part of that effort,” she added.
Both KEYNOTE-189 and CheckMate-227 increase “our understanding of the distinct molecular subtypes of lung cancer,” Dr. Hellmann said. “They are a huge step forward.”
To continue this progress, Dr. Herbst encouraged physicians to enroll their patients in clinical trials, including those in NCI’s National Clinical Trials Network, so that researchers can learn more about the distinct molecular subtypes of lung cancer and how to treat the disease.
This will take time, he added in an interview later. “We spent 20 years personalizing targeted therapies, and we are now moving toward personalized immunotherapies,” he said.
Wheat is the grain on which Western civilization was built. It’s been used for thousands of years as the foundation of our diet. But 1 out of 100 Americans has a condition called celiac disease, which is an intolerance to wheat, barley and rye. Its symptoms can be subtle, but if you don’t stick to a gluten-free diet you could be damaging your body and not even know it. More from Mayo Clinic.
Mark Truty, M.D., a Mayo Clinic surgeon specialized in treatment of pancreatic cancer, discusses the evaluation, diagnosis, and treatment of pancreatic cancer. Dr. Truty emphasizes that in 2013; approximately 45,000 patients were diagnosed with pancreatic cancer. Today, with Mayo Clinic’s research and modern approach to multimodal surgical management of pancreatic cancer, patients who previously may have had very little hope, now have a greater chance of long-term survival.
For more information, visit: http://www.mayoclinic.org/diseases-conditions/pancreatic-cancer/care-at-mayo-clinic/why-choose-mayo-clinic/CON-20028153/?mc_id=youtube
There are proven treatments that help people stop smoking. Medications and supportive discussion with a health care provider and counseling with a specialist will greatly increase your chances for stopping. In this video, health care providers from the Mayo Clinic describe medication and counseling options and explain how they work to help smokers stop smoking Patients tell how treatment provided for them the help they needed to become and stay smoke-free. There is effective treatment for anyone who smokes. Visit the Mayo Clinic website. www.mayoclinic.org/ndc-rst/
For some people it is very hard to stop smoking. In this video experts from the Mayo Clinic explain why. The video illustrates the way in which cigarettes deliver nicotine to the brain causing changes in the brain that lead to addiction. When a person stops smoking they often experience difficult withdrawal symptoms and powerful urges to smoke. The urges and withdrawal symptoms make quitting very hard for many smokers. But hope and help for smokers can be found at the Mayo Clinic website, http://www.mayoclinic.org/ndc-rst/
Multiple myeloma is a cancer of the plasma cells, which are found in the bone marrow or blood-producing tissue that fills spaces within the bones. In this video, Mayo Clinic hematologist Dr. David Dingli explains the role stem cell transplants play in treating multiple myeloma and the process patients can expect to undergo.
June 28, 2018 – 3HP for Latent TB Infection Treatment
CDC released updated recommendations for use of once-weekly isoniazid-rifapentine for 12 weeks (3HP) for treatment of latent tuberculosis (TB) infection. The updated recommendations support expanded use of an effective, shorter, treatment regimen to reach even more people with latent TB infection. The 3HP regimen can help remove current barriers to latent TB treatment for both patients and providers.
A living nightmare. That’s how the woman you’re about to meet describes her experience with a rare disease called myasthenia gravis. Visit http://mayocl.in/2md660k for more information on care at Mayo Clinic or to request an appointment.
The condition caused her to become so weak she couldn’t walk, talk or swallow. After seeing several doctors, she ended up at Mayo Clinic where medication and a minimally invasive approach to surgery helped her regain her strength and her life.