ESMO Virtual Congress 2020: Efficacy and Safety of Avelumab with Gemcitabine/Carboplatin (CG) vs CG Alone in Patients with Unresectable or Metastatic Urothelial Carcinoma Who are Ineligible to Receive Cisplatin-Based Therapy

( The current first-line standard of care therapy for advanced urothelial carcinoma patients with good performance status and kidney function is cisplatin-based chemotherapy. However, up to 50% of advanced urothelial carcinoma patients are not medically eligible for cisplatin therapy. Options, in this case, include carboplatin-based chemotherapy, or atezolizumab or pembrolizumab if patients have high levels of PD-L1 expression as assessed by the appropriate companion diagnostic test. In this presentation, Dr. Valderrama presented data from a multi-center phase 2 trial evaluating the efficacy of the anti-PD-L1 antibody avelumab in combination with carboplatin/gemcitabine chemotherapy as compared to carboplatin-based chemotherapy alone in patients who are ineligible to receive cisplatin.

The study design is shown below, avelumab was administered for two cycles as induction therapy, then in combination with carboplatin/gemcitabine, and finally as maintenance until progression or development of unacceptable toxicity. The primary endpoint was overall response rate.


Patient characteristics were well-balanced between treatment arms, including rates of visceral metastatic disease, location of metastatic disease, and reasons for being deemed cisplatin-ineligible.


The overall response rate from combination IO/chemotherapy was 57.1%, which was similar to that of chemotherapy alone (53.5%). The response rate of carboplatin/gemcitabine therapy was higher than expected from historical data, and parallels the chemotherapy response rates seen in the IMVigor130 trial. 31% of patients in the avelumab arm progressed or died before or at the time of first planned response assessment, relative to 9% in the chemotherapy alone arm. No imbalance was observed in known adverse prognostic factors between groups. At a median follow-up of 15 months, there was no difference in progression free survival (PFS) or overall survival (OS).


Even after censoring all patients who died within 30 days (6 patients), no differences in PFS or OS were observed though more patients in the combination arm were alive at 15 months


The observed toxicities were consistent with those previously seen with each therapy. Overall, these data suggest that induction immunotherapy with avelumab prior to carboplatin-based chemotherapy is not an appropriate strategy in cisplatin-ineligible advanced urothelial carcinoma.

Presented by: Begona P. Valderrama, Department of Oncology, Hospital Universitario Virgen del Rocío, Seville, Spain

Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute at the European Society for Medical Oncology Virtual Congress, ESMO Virtual Congress 2020 #ESMO20, 18 Sept - 21 Sept 2020 

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