Five-year results of immunotherapy for lung cancer: A discussion with Dr. Julie Brahmer

Background
In December 2014, investigators reported the first clinical trial results for the immune checkpoint inhibitor nivolumab (Opdivo) for the treatment of patients with advanced squamous non-small cell lung cancer (NSCLC). At the recent American Association for Cancer Research (AACR) Annual Meeting in April 2017, researchers presented long-term results using nivolumab in the same cohort of patients with NSCLC.

In this interview, lead researcher Dr. Julie Brahmer of Johns Hopkins School of Medicine in Baltimore, MD, discusses these results and what they mean for patients with lung cancer.

MDLinx: What kind of long-term results did this trial find?

Dr. Brahmer: We were able to show that the five-year estimated overall survival rate was 16% in a group of 129 patients who were enrolled in the second human clinical trial of nivolumab. These were patients with lung cancer who had progressed after chemotherapy.

Historically, we typically tell patients with metastatic lung cancer that their five-year survival rate is approximately 4%. But now with immunotherapy, there are a group of patients who can be alive a long time after their diagnosis, even without treatment.

MDLinx: You stopped nivolumab after two years if the patient responded to the treatment or remained stable. Tell me about these patients.

Dr. Brahmer: If the patient was doing well after two years, the treatment was automatically stopped and the patient was then followed. Treatment was also stopped early if patients had side effects. Out of 16 patients, 12 received no further therapy after the nivolumab was stopped and had no evidence of progression at the time of the last follow-up. Only four patients had to stop early because of side effects and those patients also didn’t require any further treatment.

This trial indicates that there are a group of patients for which we can stop treatment at two years and follow them, and the response is maintained and the disease won’t progress.

MDLinx: What did these patients who survived have in common?

Dr. Brahmer: We looked at the different characteristics to try to see if anything predicted which patients would be long-term survivors, and we didn’t see a consistent pattern or characteristic. It really didn’t matter what subtype of lung cancer they had or what their histology was. It didn’t matter what biomarker they had or didn’t have, or what their previous therapy was.

However, the majority of patients who lived beyond five years did have initial responses to nivolumab, not just stable disease. This kind of gives us the first glimpse that if immunotherapy does work, it can work for a very long time and patients don’t need long-term treatment.

We’ll find out more about this over the next several years as the phase 3 trials start reporting their long-term survival rates.

MDLinx: What has been the response from patients who survived five years or longer?

Dr. Brahmer: It’s certainly life changing because they never expected to be alive and doing well this far out. It’s truly a credit to these patients that they were willing to take a chance on this type of drug because, back when the trial began, there was no certainty whether or not this [immunotherapy] would work.

For lung cancer patients, there haven’t been a whole a lot of options outside of the new drugs that are being developed for patients with a specific mutation in their cancer. Immunotherapy is a bit more wide reaching and it gives a lot more patients another treatment option besides chemotherapy.

MDLinx: While you were at the AACR 2017 Annual Meeting, what was the most promising research you heard from other presenters?

Dr. Brahmer: A trial presented by Dr. David McDermott looked at gene signatures for patients with kidney cancer to potentially predict which type of treatments would be best for that particular patient. Also, Dr. Solange Peters presented some information about tumor mutation burden and immunotherapy in lung cancer patients, and this seemed to be a better predictor of benefits for patients than PD-L1 status.

About Dr. Brahmer: Julie R. Brahmer, MD, MSc, is the Director of the Thoracic Oncology Program and Associate Professor of Oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. She also directs the Kimmel Cancer Center on the Johns Hopkins Bayview campus and is co-principal investigator on Johns Hopkins’ National Clinical Trials Network.

This study was funded by Bristol-Myers Squibb (BMS), the maker of Opdivo.