Practical Perspectives in the Treatment of Small-Cell Lung Cancer - Episode 2
Mark Socinski, MD: With both of those being anti–PD-L1 antibodies, I’m going to ask Dr Liu, we are coming off the tail of our first virtual ASCO [the American Society of Clinical Oncology annual] meeting this year. And at that meeting we saw the presentation of 2 trials with PD-1 inhibitors, KEYNOTE-604 with pembrolizumab, and the ECOG-ACRIN 5161 trial, which was actually a phase 2 trial with nivolumab. Can you walk us through those and give us your impressions?
Stephen Liu, MD: Yes. These are 2 randomized studies and we saw results for the first time. The phase 3 trial you mentioned, KEYNOTE-604, was presented by Charles Rudin, [MD]. This was a very well-designed randomized, placebo-controlled large phase 3 trial. It included patients with previously untreated stage IV small cell lung cancer. All patients received platinum/etoposide, allowed either carboplatin or cisplatin, with a 1:1 randomization to concurrent pembrolizumab or placebo, followed by maintenance [pembrolizumab] or placebo. The study had 453 patients, of note, the vast majority, about 70%, received carboplatin. And it had dual primary end points of progression-free survival [PFS] and overall survival [OS]. What we saw at ASCO 2020 was the final analysis, and in that analysis KEYNOTE-604 was positive in that it hit its progression-free survival end point. The PFS favored pembrolizumab a median of 4.8 from 4.3 [months], the hazard ratio there was 0.73, the 1-year PFS rate from 5% with placebo to 15% with [pembrolizumab].
Unfortunately, overall survival did not cross the threshold for superiority. There was a numeric difference, median from 9.7 to 10.8 [months], hazard ratio of 0.80, but it did not cross that statistical threshold for a positive OS benefit. It’s interesting, if you take away 1 patient who inadvertently received the wrong treatment, it was a positive trial, just to show how close it was. We learned from KEYNOTE-604 there is activity there, comparable, in the same ballpark, as we saw with PD-L1 in IMpower133 for atezolizumab, and in CASPIAN for durvalumab. But unfortunately, this will not impact practice because it did not improve survival; while the trend was encouraging, it didn’t quite get there.
The ECOG-ACRIN 5161 was a randomized phase 2, through the cooperative group. It accrued remarkably fast, and this study looked at platinum/etoposide with or without nivolumab. No placebo, choice of platinum, this was a smaller study, a phase 2, 160 patients, and this study accrued in 7 months. Primary end point was progression-free survival, and that improved with nivolumab from 4.7 to 5.5 [months]. It’s a hazard ratio of 0.68. Even though a relatively modest size study, it was able to show a PFS benefit and was able to show a survival benefit. The OS hazard ratio there was 0.73. This was a smaller phase 2 positive for both PFS and OS. In a world where we have multiple randomized phase 3 trials showing an OS benefit with atezolizumab, durvalumab, unfortunately, no immediate impact in our clinic.
Transcript Edited for Clarity