Randomized phase II/III trial assessing gemcitabine/carboplatin (GC) and methotrexate/carboplatin/vinblastine (M-CAVI) in patients (pts) with advanced urothelial cancer (UC) “unfit” for cisplatin based chemotherapy (CHT): Updated phase II results and risk group analysis of EORTC study 30986

Abstract

5031 Background: The primary objective of the phase II part of this study was to evaluate activity and safety of two CHT combinations in pts with UC “unfit” for cisplatin based chemotherapy. Methods: CHT naïve pts with measurable disease and an impaired renal function (GFR<60 but >30 ml/min) and/or performance status 2 were randomized to receive either GC (G 1000 mg/m ² d1&8 and C AUC 4.5) q21days or M-CAVI (M 30 mg/m² d1&15&22, CA AUC 4.5 d1 and VI 3 mg/m² d1&15&22) q28 days. A two stage Bryant and Day design was used with endpoints response and severe acute toxicity (SAE) which were evaluated with respect to renal function, performance status and Bajorin risk groups. Results: 3 of 178 pts from 28 institutions who were ineligible or did not start treatment are excluded. 16/175 pts received only 1 cycle for reasons other than progression or toxicity. SAEs were mucositis gr3, 1.1% vs 5.7%, thrombocytopenia 3/4 with bleeding 18.1% vs 1.1%, neutropenic fever 3/4 5.7% vs 14.9%, renal toxicity 3/4 5.7% vs 8.0% and death due to treatment 2.3% vs 4.6% for GC and M-CAVI, respectively. Overall response rates (ORRs) and SAEs by treatment arm and risk groups are summarized below (see table). Conclusions: Both combinations are active in this well defined group of purely unfit patients. However in pts with PS2 and GFR<60 ml/min or Bajorin risk group 2, ORRs with GC and M-CAVI are low and toxicity high. Alternative treatment modalities should be sought in this subgroup of very poor risk patients. ORRs and SAEs by treatment arm and risk groups Only 1 cycle n=16/175 (%) ORR (%) SAEs (%) PS2 or GFR<60 7/129 (5) 40 16 PS2 & GFR<60 9/46 (20) 26 26 Bajorin 0 4/68 (6) 47 16 1 2/58 (3) 38 16 2 10/49 (20) 20 24 GC 6/88 (7) 42 14 M-CAVI 10/87 (11) 31 23 ORR=overal response rates; SAE=severe acute toxicity Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Eli Lilly