ASCO GU 2020: Preliminary Results of the GETUG/AFY VESPER Trial on Toxicity and Pathological Responses

San Francisco, CA (UroToday.com) The interesting phase 3 randomized trial comparing dd-MVAC to GC in muscle invasive urothelial bladder cancer (MIUBC) was presented by Dr. Stephane Culine. The standard of care for MIUBC in 2020 is cystectomy and perioperative chemotherapy with level one evidence supporting neoadjuvant chemotherapy,¹ and low evidence supporting adjuvant chemotherapy. The survival benefit has been shown to be restricted to cisplatin-based chemotherapy. There are 2 regimens that have been frequently used: dd-MVAC and GC. The associated ypT0N0 rate has been shown to be 10-50% in phase 2 trials.²

The VESPER trial aimed to analyze what the optimal perioperative chemotherapy regimen is. This was a randomized phase 3 trial hypothesizing that dd-MVAC improved 3-year progression free survival (PFS) by 10% when compared to GC. The authors aimed to accrue 500 patients with the secondary endpoints being toxicity, pathological responses and overall survival (OS).

The inclusion criteria were:

Pure or mixed urothelial bladder cancer (neuroendocrine was excluded)
ECOG performance status <2
All criteria for cisplatin eligibility had to be met
Informed consent

AND

>=T2, N0 (lymph node<=10 mm on CT scan), M0 for patients receiving neoadjuvant chemotherapy
OR >=T3 OR pN+ and M0 for patients receiving adjuvant chemotherapy

Patients received chemotherapy according to the protocol showed in figure 1, and surgery within 8 weeks in the neoadjuvant chemotherapy cohort.

Figure 1- Trial design:

The trial took place between February 2013 and March 2018. A total of 500 patients form 28 French cancer centers were accrued. 493 patients were available for intention to treat analysis. A total of 56 patients (11%) and 437 (89%) received adjuvant and neoadjuvant chemotherapy, respectively. The patients’ characteristics are shown in Table 1 and the associated hematological and non-hematological toxicities are shown in table 2, and 3, respectively.

Table 1 – Patient characteristics:

Table 2 – Hematological toxicities:

Table 3 – Non-hematological toxicities:

In the adjuvant cohort, 19% and 60% of the patients received less than 4 cycles of GC and less than 6 cycles of dd-MVAC, respectively. In the neoadjuvant cohort receiving GC, 16% and 90% received less than 4 cycles and underwent surgery, respectively. In the neoadjuvant cohort receiving dd-MVAC 39% and 91% received less than 6 cycles and underwent surgery, respectively.

The pathological results were quite interesting, showing a clear advantage to the dd-MVAC cohort in the rate of complete response, non-muscle invasive disease, and organ confined disease (Table 4).

Dr. Culine concluded that grade >=3 complications (anemia, febrile neutropenia, asthenia, and nausea/vomiting) were more common in the dd-MVAC arm. A higher local control rate was achieved in the dd-MAC arm.

We eagerly await the final PFS and OS results expected to be released in 2021.

Table 4- Pathological responses:

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

Written By: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA @GoldbergHanan at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California

References:

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