{'fraction_non_alphanumeric': 0.05915894511760513, 'fraction_numerical': 0.044547398431931576, 'mean_word_length': 4.763860369609857, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
PD52-03 A MULTICENTER PHASE 1B/2 STUDY OF NEOADJUVANT PEMBROLIZUMAB AND CISPLATIN CHEMOTHERAPY FOR MUSCLE INVASIVE UROTHELIAL CANCER

INTRODUCTION AND OBJECTIVES: We sought to assess if pembrolizumab (pembro) improves the pathologic response rate in locally advanced urothelial carcinoma (UC) when combined with gemcitabine (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, ⩽pT1N0M0) has been noted for neoadjuvant dose dense MVAC at ∼44%. METHODS: Cisplatin eligible patients with cT2-4aN0M0 UC were treated with pembro 200mg q3wks on day 8 for 5 doses; with C (70mg/m2) day 1, and G (1000mg/m2) days 1 and 8 of a 21-day cycle, for 4 cycles; followed by radical cystectomy (RC). Minimum criteria for evaluation of safety was one dose pembro and for efficacy two doses and RC. The primary endpoint was PaIR of ≥48%, and secondary endpoints included safety and tolerability, RC rate, relapse free-, disease specific-, and overall survival. RESULTS: 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. CONCLUSIONS: 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. Clinical trial identification Clinicaltrials.gov: NCT02365766 Source of Funding: Hoosier Cancer Research Network