KEYNOTE-361 Study for Advanced Urothelial Carcinoma

A review of the KEYNOTE-361 study and recent findings of the post-hoc analysis looking at long-term results of pembrolizumab vs chemotherapy as first-line treatment for advanced urothelial carcinoma.

Petros Grivas, MD, PhD: Another big question in the frontline setting, as I mentioned, concerns the concurrent chemotherapy–I/O [immuno-oncology] combination, or if immunotherapy alone can beat chemotherapy. KEYNOTE-361, like IMvigor130, was designed very nicely to address these 2 questions. KEYNOTE-361 had 3 arms. Arm A was a combination of concurrent chemotherapy plus pembrolizumab; arm B was pembrolizumab alone, or monotherapy; arm C was chemotherapy alone. For arm A, or chemotherapy and pembrolizumab, vs arm C, chemotherapy and pembrolizumab vs chemotherapy, there was no significant overall survival [OS] or PFS [progression-free survival] benefit with the addition of pembrolizumab to chemotherapy, and that was a very interesting and surprising finding. The addition of pembrolizumab to chemotherapy did not significantly prolong PFS or OS. There was, of course, a little more toxicity, and obviously cost, but no significant survival benefit with the addition.

The second question was can pembrolizumab alone vs chemotherapy be effective? In all patients in the intent-to-treat population, regardless of PD-L1, pembrolizumab was not significantly superior to chemotherapy. Even in the population of patients with CPS [combined positive score] 10 or higher—so PD-L1–high patients—pembrolizumab was not statistically significantly different from chemotherapy. This tells us that chemotherapy by itself holds its position, in the frontline setting, as initial therapy, and we have to figure out why this is the case. More biomarker work is needed. Based on the data from IMvigor130 and KEYNOTE-361, if you start with chemotherapy, you give it alone. Then you have, as I mentioned, the level 1 evidence of the JAVELIN Bladder 100 trial, where giving avelumab maintenance in those who achieve response or stable disease to platinum-based chemotherapy is an option.

Transcript edited for clarity.

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