ASCO GU 2020: Randomized Phase III trial for Treatment of Muscle-Invasive Urothelial Bladder Cancer: Preliminary Results of the GETUG/AFU V05 VESPER Trial on Toxicity and Pathological Responses

San Francisco, California (UroToday.com) The standard of care for muscle-invasive urothelial bladder cancer (MIBC) in 2020 is a radical cystectomy with perioperative chemotherapy (CT). Level 1 evidence supports the use of neoadjuvant CT. Lower level evidence exists for adjuvant CT, but nevertheless, it is frequently used. The two peri-operative chemotherapy regimens with the strongest data are (i) gemcitabine and cisplatin (GC) every three weeks; (ii) dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin every two weeks (ddMVAC).

The GETUG/AFU V05 VESPER trial sought to determine the optimal perioperative chemotherapy regimen by randomizing 500 men to GC versus ddMVAC. The main hypothesis was that ddMVAC improves 3-year progression-free survival by 10% compared to GC. Notable inclusion criteria were pure or mixed UBC (neuroendocrine excluded), ECOG PS < 2, cisplatin eligible. Patients with cT2-4N0M0 were eligible for neoadjuvant CT; patients with pT2-4 or N+ (node-positive) M0 disease were eligible for adjuvant CT. This pre-planned interim analysis reported on the secondary endpoints of toxicity and pathological response.

GETUGAFU V05 VESPER trial design

500 patients were randomized between February 2013 and March 2018; 493 were available for the intention-to-treat analysis. Eighty-nine percent of patients received neoadjuvant CT and 11% received adjuvant CT. Arms were well-balanced for age, sex, performance status, creatinine clearance, and clinical/pathological stage.

GETUGAFU V05 VESPER patient characteristics

Notable differences in toxicity occurred. The following grade 3 or higher toxicities were more frequent in the ddMVAC arm than the GC arm: amemia (22% versus 8%; p = 0.00002), gebrile neutropenia (7% versus 2%; p = 0.05), nausea/vomiting (10% versus 3%; p = 0.03), and asthenia (14% versus 4%; p = 0.0002). There was 1 death on the GC arm and 3 deaths on the ddMVAC arm, which was not statistically significantly different (p = 0.62).

Treatment delivery rates in the adjuvant setting were significantly different. Nineteen percent of patients randomized to receive GC received less than the planned four cycles of GC compared to 60% of patients on the ddMVAC arm who received less than the planned six cycles. Median time from surgery to CT was similar in the GC arm (71 days) and ddMVAC arm (77 days). A similar trend was observed in the neoadjuvant setting where 16% of patients did not complete four cycles of GC compared to 39% of patients who did not complete six cycles of ddMVAC. Among patients randomized to GC, the median number of cycles received was four and 90% underwent surgery. On the ddMVAC arm, the median number of cycles received was six (11% received five cycles, 14% received four cycles, 14% received three cycles or fewer) and 91% underwent surgery. Median time to surgery was similar in the GC arm (48 days) and ddMVAC arm (51 days).

Pathological response rates differed significantly between the arms, favoring ddMVAC. Complete responses were seen in 42% of patients receiving ddMVAC compared to 36% of patients receiving GC (p = 0.02). Rates of non-muscle invasive disease (63% versus 49%; p = 0.007) and organ-confined disease (77% versus 63%; p = 0.002) were also significantly higher in patients treated with ddMVAC than GC.

GETUGAFU V05 VESPER pathological response

Conclusions from the pre-planned interim analysis of safety and pathological response from the GETUG/AFU V05 VESPER Trial are as follows:

  • Treatment delivery was suboptimal in the adjuvant group
  • Grade 3 or higher anemia, febrile neutropenia, asthenia, nausea, and vomiting were more frequently observed in the ddMVAC arm
  • A higher local control rate was achieved in the ddMVAC arm
  • Progression-free survival and overall survival data will be reported in 2021

Presented by: Stephane Culine, MD, PhD, Medical Oncology, Hôpital Saint-Louis, Assistance Publique – Hôpitaux de Paris, Paris, France

Written by: Jacob Berchuck, MD, Medical Oncology Fellow at the Dana-Farber Cancer Institute, Boston, Massachusetts, Twitter: @jberchuck at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California

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