Immunotherapy Agents, Combinations to Compete for Frontline NSCLC

Lisa Miller
Published Online: Monday, Apr 17, 2017

Sukhmani Padda, MD

Sukhmani Padda, MD

Immunotherapy agents, both as monotherapy and in combination, are emerging in the pipeline of non–small cell lung cancer (NSCLC) and could end up competing as frontline treatment for patients, explains Sukhmani Padda, MD.  

For example, the PD-1 inhibitor pembrolizumab (Keytruda) is the sole immunotherapy agent approved in the first-line setting for patients with NSCLC; however, many other immunotherapy agents and combination regimens are in development that are aimed at this line of therapy.

In a presentation during the 4th Annual Miami Lung Cancer Conference®, Padda, assistant professor of medicine, Stanford University Medical Center, addressed the optimal immunotherapy choices for select patients versus standard platinum-based chemotherapy, as well as ongoing clinical trials of agents looking to join pembrolizumab in the frontline setting.

Following her presentation, Padda sat down for an interview with OncLive to discuss the status of ongoing trials participating in this race to the frontline in lung cancer.

OncLive: What are the latest developments in immunotherapy in the frontline setting in lung cancer?

Padda: It’s been a really exciting time in lung cancer because we finally have something for patients who don’t have a molecular driver mutation, other than chemotherapy. Just last year, pembrolizumab, which is a PD-1 checkpoint inhibitor, was approved for a subgroup of patients with NSCLC. We should go through the eligibility because it’s really important: these are patients who have no evidence of EGFR mutations in their tumor or ALK rearrangements, and a high level of PD-L1 expression, which was defined as ≥50%.

In that specific population, looking at a primary endpoint of progression-free survival [PFS], pembrolizumab beat chemotherapy with a hazard ratio of 0.5. That was a really nice development, as it is nice to have something else to offer our patients with lung cancer.

Are there any other immunotherapy-based regimens in the pipeline that are promising?

As you can imagine, there is a lot of excitement right now around immunotherapy. Essentially, every permutation and combination you can imagine is being tested. We know that there are a variety of PD-1 and PD-L1 immune checkpoint inhibitors, there are also many other checkpoint inhibitors, and even checkpoint agonists, that are all being targeted. We’ll have to see who, in the end, wins the race.

The furthest along in development is the combination of chemotherapy plus immunotherapy in the first-line setting. This was part of the KEYNOTE-021 study, specifically cohort G. This was a randomized phase II study that looked at the combination of

carboplatin/pemetrexed plus pembrolizumab versus carboplatin/pemetrexed alone. The trial did allow for crossover to the combination arm. The primary endpoint for that study was overall response rate, and so they did see an enhanced overall response rate with the combination of immunotherapy and chemotherapy in that setting, around 55% versus 30% with chemotherapy alone.

If you look at the waterfall plots overall, though, there does seem to be deeper responses when you give the combination of chemotherapy and immunotherapy and overall less patients progress. I think it’s promising in that setting that potentially you could get a deeper response and perhaps in a shorter timeframe.


View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Medical Crossfire®: Leveraging Liquid Biopsies in Tumor Characterization for NSCLC TherapyJan 31, 20181.5
Oncology Best Practice™: Choosing Therapies for Patients with EGFR-Mutant Lung Cancers: More Options... More Decisions... Better OutcomesFeb 28, 20182.0
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