Randomized phase III trial of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC) as perioperative chemotherapy for muscle invasive urothelial bladder cancer (MIUBC): Preliminary results of the GETUG/AFU V05 VESPER trial on toxicity and pathological responses.

Abstract

437 Background: The optimal perioperative chemotherapy regimen for patients (pts) with MIUBC is not defined. Methods: Between February 2013 and February 2018, 494 pts were randomized in 28 French centres and received either 4 cycles of GC every 3 weeks or 6 cycles of dd-MVAC every 2 weeks before surgery (neoadjuvant group) or after surgery (adjuvant group). The primary endpoint was the progression-free survival at 3 years. Secondary endpoints included toxicity, pathological responses and overall survival. Results: In the neoadjuvant group, 218 pts received dd-MVAC and 219 pts GC. The median number of cycles was 6 (0-6) and 4 (1-4), respectively. 60% of pts received 6 cycles in the dd-MVAC arm, 84% received 4 cycles in the GC arm. 199 pts (91%) and 198 (90%) pts underwent surgery, respectively. Complete pathologic responses (ypT0pN0) were observed in 84 (42%) and 71 (36%) pts, respectively (p=0.02). An organ-confined status (<ypT3pN0) was obtained in 154 (77%) and 124 (63%) pts, respectively (p=0.002). In the adjuvant group (57 pts), the median number of cycles was 5 (1-6) and 4 (1-4), respectively. 40% of pts received 6 cycles in the dd-MVAC arm, 60% received 4 cycles in the GC arm. Most of CTCAE grade ≥ 3 toxicities concerned hematological toxicities. At least one of these where reported for 125 (50%) pts in the dd-MVAC group and 134 (54%) pts in the GC group (p=NS). Gastrointestinal (GI) grade ≥ 3 disorders were more frequently observed in the dd-MVAC arm (p<0.0001) as well as grade ≥ 3 asthenia (p<0.00001). Four deaths (3 in the dd-MVAC) occurred during chemotherapy. Conclusions: Complete pathological responses and organ-confined status were more frequently observed in the dd-MVAC arm. Toxicity was manageable with more severe asthenia and GI side effects in the dd-MVAC arm. Clinical trial information: 2012-000563-25.