(Merck) Jan 6, 2020 - Merck, known as MSD outside the United States and Canada, today announced that the Phase 3 KEYNOTE-604 trial investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy met one of its dual primary endpoints of progression-free survival (PFS) in the first-line treatment of patients with extensive stage small cell lung cancer (ES-SCLC). In the study, treatment with KEYTRUDA in combination with chemotherapy (etoposide plus cisplatin or carboplatin) resulted in a statistically significant improvement in PFS compared to chemotherapy alone (HR=0.75 [95% CI, 0.61-0.91]), which was observed at a prior interim analysis.Read Article
H. Jack West, MD (Posted: January 07, 2020)
Perhaps a bit surprising for pembro, which has had the luck or efficacy to usually be just a shade better than others in its class, but this wasn't going to be a high stakes win even if the trial had been positive for OS. To be clear, KEYNOTE-604 being positive for PFS but negative for OS is definitely not a victory when atezolizumab and durvalumab have already demonstrated positive results for OS in the same setting. At best, a third and very redundant entrant into the same market, unless it had looked significantly better than the others.
The fact that this trial was negative for OS shouldn't leave us agonizing about how pembro is meaningfully different or inferior. In fact, with a HR of 0.80 that barely missed statistical significance, these results are very similar to IMpower133 and CASPIAN (with atezo and durva, respectively), but those came out just a tiny shade better for OS, with results falling on the statistically significant side in those cases, leaving some debating whether the improvement is enough to be truly impressed by those results. As it is, the pembro results in ES-SCLC are very concordant but don't support the concept that pembro is invariably a bit better than other competing anti-PD1 immune checkpoint inhibitors.