Dr Chaft Discusses Ipilimumab plus Nivolumab for PD-L1-low NSCLC

At the virtual 2021 Personalized Therapies in Thoracic Oncology meeting, Jamie E. Chaft, MD Associate Attending Physician Thoracic Oncology Memorial Sloan Kettering Cancer Center, engaged in a stimulating debate regarding how to handle PD-L1<50% in patients with non-small cell lung cancer (NSCLC).

While her opponent, Aaron Lisberg, Assistant Professor of Clinical Medicine, University of California, Los Angeles, favored pembrolizumab plus histology-specific chemotherapy, Dr Chaft argued for ipilimumab/nivolumab with or without chemotherapy.

“Dr Lisberg here on the OS [overall survival] data, however, I think it’s the PFS [progression-free survival] data that really tells the story here. What we are looking for is the tail on the curve.” Dr Chaft explained. 

When observing the results of Keynote-407, a study on pembrolizumab plus chemotherapy in patients with PD-L1 <1%, there was little PFS data available. 

“We should be striving for durable tails on the curve, splittings of medians that are more than a month or two,” she continued.

On the contrary, CheckMate 9LA, a randomized study on ipilimumab/nivolumab with two cycles of chemo v.s chemo alone, showed superior PFS results. In patients with a PD-L1 expression of 1% or more, PFS was 7.0 months in the ipilimumab/nivolumab group, compared to 5.0 in the chemotherapy group (95% CI, 0.67 [0.53-0.84]). Additionally, Dr Chaft points out that the PFS curve in patients who are PD-L1 negative was nearly identical, suggesting that adding a CTLA4 (such as ipilimumab) can overcome innate resistance to checkpoint inhibition.

Furthermore, follow-up from the Checkmate 227a trial showed that patients with a PD-L1 >1% had a more durable PFS. Among patients receiving ipilimumab plus nivolumab, 34% had a PFS of 36 months, compared to 0% in the chemotherapy group.

“I will conclude by saying, for tumors that are PD-L1 negative you need to find the right tail for your patient, and for me, that’s certainly ipilimumab and nivolumab with or without chemo and much less likely chemo plus PD-1 or PD-L1,” concluded Dr Chaft.—Alexandra Graziano