Melissa Johnson, MD
PD-1/PD-L1 inhibitors continue to change the armamentarium of non–small cell lung cancer (NSCLC) treatment, especially with the May 2017 frontline approval of the combination of pembrolizumab (Keytruda) and pemetrexed/carboplatin regardless of PD-L1 expression status.
Although the promising findings of the phase III KEYNOTE-024 trial led to the October 2016 FDA approval for single-agent pembrolizumab in the frontline setting, results of the CheckMate-026 trial—which explored frontline nivolumab (Opdivo) in patients with NSCLC—were disappointing as overall survival (OS) was with chemotherapy and the PD-1 inhibitor, also questioning the utility of PD-L1 as a biomarker.
However, results of an analysis of CheckMate-026 presented at the 2017 AACR Annual Meeting showed that patients who had high tumor mutation burden derived an enhanced benefit from nivolumab compared with platinum-doublet chemotherapy. Of the patients with high tumor mutation burden, the median progression-free survival (PFS) improved to 9.7 months versus 5.8 months (HR, 0.62; 95% CI, 0.38-1.00) and the objective response rate was higher with nivolumab versus chemotherapy (46.8% vs 28.3%).
Melissa Johnson, MD, associate director, Lung Cancer Research, Sarah Cannon Research Institute, described the impact of immunotherapy for patients with NSCLC—those with both high and low levels of PD-L1 expression—and how the treatment and the role of PD-L1 will continue to progress in the coming years in an interview during the 2017 OncLive®
State of the Science Summit™ on Advanced Non–Small Cell Lung Cancer.
OncLive: What is the current role of immunotherapy in NSCLC?
Immunotherapy is currently approved for second-line use in all patients with lung cancer, but about 6 months ago, it was also approved for patients in the frontline setting whose tumors express high levels of PD-L1 at 50% or greater. It’s pembrolizumab that is approved for those patients.
What emerging regimens are in the pipeline?
Pembrolizumab is approved for patients in the frontline setting who have tumors that express high levels of PD-L1 at more than 50%, but that is only about 30% of frontline patients with lung cancer. That leaves about 60% that need to be treated either with immunotherapy plus chemotherapy or PD-L1 inhibitors in combination with other checkpoint inhibitors such as anti–CTLA-4 inhibitors. PD-1 plus CTLA-4 is a strategy that’s already been approved for the treatment of patients with metastatic melanoma, and many oncologists have good experience using that regimen.
We have a number of clinical trials right now that are evaluating that strategy for patients with lung cancer in the frontline setting, across a number of sponsors. Merck is evaluating pembrolizumab plus ipilimumab (Yervoy), Bristol-Meyers Squibb is evaluating nivolumab plus ipilimumab, and AstraZeneca Medimmune is looking at durvalumab (Imfinzi) plus tremelimumab.
How has the frontline approval of pembrolizumab changed the landscape?
It cannot be overstated that it has really changed the standard of care for patients with newly diagnosed lung cancer, which is a pretty dramatic statement. However, the idea that you can give patient a single-agent therapy that doesn’t make them lose their hair or give them side effects like nausea, cytopenia, or neuropathy is very significant.
It has also led to improved survival, which is amazing, and something that is a hope for every clinical trial. It [has] also meant that patients need more tissue at diagnosis in order to know the best treatment. In the past, we needed tissue for molecular testing. Now we also need it for PD-L1 testing. Therefore, we are having more and more conversations with our pulmonologists, pathologists, and sometimes surgeons with getting enough tissue at diagnosis to enable the best treatment decision from the beginning.
What is the efficacy of PD-L1 as a biomarker?
That is a good question, maybe even a controversial one. In the frontline setting, we use pembrolizumab based on its FDA approval in October 2016 for patients with PD-L1–high tumors. In the KEYNOTE-024 trial that led to that approval, it seemed to be a very reliable biomarker, as the patients with PD-L1–high expression did do better with pembrolizumab.