Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma

Thomas Powles, Se Hoon Park, Eric Voog, Claudia Caserta, Begoña P. Valderrama, Howard Gurney, Haralabos Kalofonos, Siniša Radulović, Wim Demey, Anders Ullén, Yohann Loriot, Srikala S. Sridhar, Norihiko Tsuchiya, Evgeny Kopyltsov, Cora N. Sternberg, Joaquim Bellmunt, Jeanny B. Aragon-Ching, Daniel P. Petrylak, Robert Laliberte, Jing WangBo Huang, Craig Davis, Camilla Fowst, Nuno Costa, John A. Blake-Haskins, Alessandra di Pietro, Petros Grivas

Research output: Contribution to journalArticlepeer-review

657 Citations (Scopus)


BACKGROUND: Platinum-based chemotherapy is standard-of-care first-line treatment for advanced urothelial carcinoma. However, progression-free survival and overall survival are limited by chemotherapy resistance. METHODS: In a phase 3 trial, we randomly assigned patients with unresectable locally advanced or metastatic urothelial cancer who did not have disease progression with first-line chemotherapy (four to six cycles of gemcitabine plus cisplatin or carboplatin) to receive best supportive care with or without maintenance avelumab. The primary end point was overall survival, assessed among all patients who underwent randomization (overall population) and among those with tumors positive for programmed cell death ligand 1 (PD-L1). Secondary end points included progression-free survival and safety. RESULTS: Among all 700 patients who underwent randomization, the addition of maintenance avelumab to best supportive care significantly prolonged overall survival as compared with best supportive care alone (control). Overall survival at 1 year was 71.3% in the avelumab group and 58.4% in the control group (median overall survival, 21.4 months vs. 14.3 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.86; P = 0.001). Avelumab also significantly prolonged overall survival in the PD-L1-positive population; overall survival at 1 year was 79.1% in the avelumab group and 60.4% in the control group (hazard ratio, 0.56; 95% CI, 0.40 to 0.79; P<0.001). The median progression-free survival was 3.7 months in the avelumab group and 2.0 months in the control group in the overall population (hazard ratio for disease progression or death, 0.62; 95% CI, 0.52 to 0.75) and 5.7 months and 2.1 months, respectively, in the PD-L1-positive population (hazard ratio, 0.56; 95% CI, 0.43 to 0.73). The incidence of adverse events from any cause was 98.0% in the avelumab group and 77.7% in the control group; the incidence of adverse events of grade 3 or higher was 47.4% and 25.2%, respectively. CONCLUSIONS: Maintenance avelumab plus best supportive care significantly prolonged overall survival, as compared with best supportive care alone, among patients with urothelial cancer who had disease that had not progressed with first-line chemotherapy. (Funded by Pfizer and Merck [Darmstadt, Germany]; JAVELIN Bladder 100 ClinicalTrials.gov number, NCT02603432.).

Original languageEnglish
Pages (from-to)1218-1230
Number of pages13
JournalNew England Journal of Medicine
Issue number13
Publication statusPublished - 24 Sept 2020


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