PD52-03 A MULTICENTER PHASE 1B/2 STUDY OF NEOADJUVANT PEMBROLIZUMAB AND CISPLATIN CHEMOTHERAPY FOR MUSCLE INVASIVE UROTHELIAL CANCER

Abstract

INTRODUCTION AND OBJECTIVES: We sought to assess if pembrolizumab (pembro) improves the pathologic response rate in locally advanced urothelial carcinoma (UC) when combined with gem-citabine (G) and cisplatin (C) neoadjuvant chemotherapy (NAC) through a multicenter phase 1b/2 chemo-immunomodulation trial. Historically, the best pathologic non-muscle invasive rate (PaIR, 48%, and secondary endpoints included safety and tolerability, RC rate, relapse free-, disease specific-, and overall survival. RESULT(S): Forty patients (pts) were accrued: median age was 65 years, 75% were male, 10% had mixed UC histology, and PD-L1 combined positive score >10 was 52%. No dose-limiting toxicities were noted in the 6 pts on phase 1b. Average number of doses given (vs intended) for pembro=4.3(5), C=3.7(4), G = 7.2(8). There was 1 death on post-RC day 9 due to mesenteric ischemia. One pt did not have RC due to adverse event (AE), gr4 thrombocytopenic purpura; UC in remission at 14mo, and 3 patients refused RC. One pt with presumed gr3 MI during cycle 4 had a negative cardiac workup and completed therapy and RC without further AE. One gr4 hyponatremia and ten gr3 events did not preclude RC (2-each thromboembolism, elevated creatinine, hyponatremia;1-each: dehydration, emesis, neutropenic fever, infection). Gr 3/4 cytopenias occurred in 57% of pts. Of 36 pts who had RC the median time to surgery was 5.3 wks from last dose. Baseline stage was cT2 51%, cT3 44%, cT4a 5%. The PaIR was 61%. Sixteen pts were downstaged to pT0 (44.4%), 3 to pTis (8.3%), and 3 to pT1 (8.3%). PaIR did not correlate with baseline PD-L1 score. At 17.4 (1.6-33.3) months median follow up, the relapse free-, overall-, and disease specific-survival, was 70%, 81%, and 90%, respectively. CONCLUSION(S): Neoadjuvant chemo-immunotherapy with pembro in locally advanced UC has manageable toxicity, a comparable time to surgery as NAC, and has improved pathologic outcomes compared to historic controls. Furthermore, the long-term effects of immunotherapy with a sustained high disease specific survival may provide control rates that warrant further study.