Never give up.
The Study: Let’s first revisit our losses. KEYNOTE-061 reported a pitiful progression-free survival (PFS) time with pembrolizumab when compared to standard paclitaxel, and KEYNOTE-059 showed that pembro gave patients more toxicity than it did durable responses. Now, the long-alluded to phase 2 CheckMate-032 trial has been published in full manuscript. 160 patients with chemo-refractory esophagogastric cancers from the U.S. and Europe (read: Western, not Asian) were treated with one of three immunotherapy regimens:  mono nivolumab 3 mg/kg,  combo nivo 1 mg/kg + ipilimumab 3 mg/kg, or the mirrored  combo nivo 3 mg/kg + ipi 1 mg/kg. The primary endpoint of objective response rates were  12%,  24%, and  8%, with no relation to PD-L1 or MSI status. Rates of PFS at 12 months were  8%,  17%, and  10%, which to be fair isn’t terrible considering the heavily pre-treated population. Unfortunately, as demonstrated time and time again, triple the ipi dose led to almost double the grade 3-4 toxicity rate, which was  17%,  47%, and  27%.
Bottom Line: This is no silver bullet, but it’s worth keeping an eye out for results of the on-going phase 3 CheckMate-649 testing the winning combo nivo 1 mg/kg + ipi 3 mg/kg in the first-line setting for esophagogastric cancers. | Janjigian, J Clin Oncol 2018