The New Frontier in NSCLC: Immuno-Oncology Combinations - Episode 1
Mark A. Socinski, MD: Hello, and thank you for joining this OncLive® Peer Exchange® titled “The New Frontier in NSCLC: Immuno-Oncology Combinations.” Although the availability of checkpoint inhibitors has transformed the treatment of advanced lung cancer, there is still a need for more effective frontline therapies and better predictive biomarkers for the majority of patients without driver mutations. We have new standards of care for patients with both metastatic and locally advanced disease, and are now entering an era of combination immuno-oncology regimens and perioperative regimens. In this OncLive® Peer Exchange®, we will talk about the latest data surrounding immunotherapy for non—small cell lung cancer, including the abstracts from the ASCO 2018 Annual Meeting, and opportunities for improving outcomes in clinical practice.
I am Dr. Mark Socinski, and I am the executive medical director and member of the Thoracic Oncology Program at the Florida Hospital Cancer Institute in Orlando, Florida.
Participating today on our distinguished panel are: Dr. Karen Kelly, associate director for clinical research, Jennifer Rene Harmon Tegley and Elizabeth Erica Harmon endowed chair in cancer clinical research, and professor of medicine at the UC Davis Comprehensive Cancer Center in Sacramento, California; Dr. Corey Langer, director of thoracic oncology at Abramson Cancer Center and a professor of medicine at the University of Pennsylvania in Philadelphia, Pennsylvania; and Dr. Benjamin Levy, an assistant professor of oncology and clinical director of medical oncology at the Johns Hopkins Sidney Kimmel Cancer Center, Sibley Memorial Hospital, in Washington, DC. Thank you all for joining us today. Let’s begin.
Corey, I’m going to rewind the clock a little bit and go back to April 16, 2018. At the AACR meeting here in Chicago, we had a session that really set a new standard of care. That was the presentation, finally, of KEYNOTE-189, which was much anticipated due to the results of KEYNOTE-021 cohort G, which you were involved with. I’m wondering if you could tell us a little bit about these studies and how they changed our world?
Corey J. Langer, MD, FACP: I think we need to wind the clock back maybe a year-and-a-half ago, to KEYNOTE-024, which really changed how we practice. Of course, that was single-agent pembrolizumab versus standard chemotherapy in individuals with 50% or higher PD-L1 expression. This trial showed an astounding improvement in response rate, progression-free survival and, ultimately, overall survival, which, at least in my opinion, exceeded my expectations when compared to other studies.
I was involved with a number of other institutions in a randomized phase II trial that asked a somewhat different question: whether adding immunotherapy to chemotherapy could potentially improve outcomes in a more unselected population. PD-L1 was collected, but it wasn’t stipulated as entry criteria. We looked specifically at the nonsquamous population in the absence of molecular aberrations. So, it wasn’t the global population. It explicitly excluded individuals with oncogenic drivers.
This was a randomized phase II trial. It only included 120 patients. Pembrolizumab/carboplatin was the backbone, 4 cycles, followed by pemetrexed maintenance indefinitely, plus or minus pembrolizumab. The pembrolizumab was grafted right on to that regimen and continued as maintenance with pemetrexed for up to 2 years. Here, too, we saw a very marked improvement in outcome, a doubling in response rate from 28% to 56% and a doubling in median progression-free survival. The latest updates show a progression-free survival that is approaching 20 months. The control arm is doing as well, or better than it had done historically.
Mark A. Socinski, MD: Better than expected, yes.
Corey J. Langer, MD, FACP: At 8.8, 9 months. Initially, there was no survival difference. One year: 75% versus 72%. As time went on, the curves started to separate. This is a pattern that we’ve seen in many of the immuno-oncology trials. Maybe there was not an immediate benefit in terms of progression-free survival or median overall survival in some of these trials, but once we hit the year mark, 18 months, 2 years, we start to see a separation. The hazard ratio dropped from 0.9 to 0.69 to 0.59. It wasn’t quite significant. It was a 1-sided alpha, so even though the P value was below 0.05, it could not be called statistically significant. But clearly, this was hypothesis generating. It clearly merited a prospective randomized phase III trial to either confirm or refute these data.
Transcript Edited for Clarity