Pembrolizumab alone or combined with chemotherapy versus chemotherapy as first-line therapy for advanced urothelial carcinoma (KEYNOTE-361): a randomised, open-label, phase 3 trial

SPS commentary:

According to a commentary, the largely negative overall results of this study and also the IMvigor130 study contrast starkly with the results of the JAVELIN Bladder 100 trial, which assessed the switch maintenance approach, whereby patients who had response or disease stabilisation with induction platinum-based chemotherapy for advanced urothelial carcinoma were randomly assigned to maintenance avelumab plus best supportive care versus best supportive care alone. This study showed significantly prolonged overall survival (median 21·4 vs 14·3 months) and progression-free survival (3·7 vs 2·0 months) with avelumab in the overall population, leading to the approval of maintenance avelumab after platinum-based chemotherapy in several countries. It notes that overall, these studies raise the challenging question of why switch maintenance immunotherapy, but not concurrent chemoimmunotherapy, prolongs overall survival in patients with advanced urothelial carcinoma. It adds the potential explanations for these findings are not clear, but proposes several hypotheses. It concludes that based on this current study and the totality of the available data, the use of concurrent chemoimmunotherapy is only experimental, whereas induction platinum-based chemotherapy followed by switch maintenance avelumab remains the standard frontline therapy in advanced urothelial carcinoma.