Advanced Bladder Cancer Survival Improved With Maintenance Avelumab

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According to an interim analysis of the phase III JAVELIN Bladder 100 trial, rates of survival among patients with advanced urothelial carcinoma who did not progress on first-line platinum-based chemotherapy were significantly prolonged by maintenance therapy with avelumab and best supportive care vs best supportive care alone. The data, presented during the Plenary Program of the ASCO20 Virtual Scientific Program, indicated the survival benefit among all patients enrolled in the trial, in patients who were PD-L1 positive, and in all prespecified subgroups.

“This study met its primary objective, demonstrating significantly prolonged overall survival with first-line maintenance avelumab and best supportive care vs best supportive care alone in the overall population and in PD-L1–positive patients whose disease did not progress on platinum-based chemotherapy. Avelumab as first-line maintenance therapy represents a new first-line standard of care for advanced urothelial cancer that has not progressed on first-line platinum-based chemotherapy,” said lead author Thomas Powles, MD, PhD, of Barts Cancer Institute, London.

“Instead of waiting for disease to progress after chemotherapy— which it will quickly do in patients with advanced urothelial cancer—adding avelumab significantly improved survival.”
— Thomas Powles, MD, PhD

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“The maintenance setting is an attractive time for using a checkpoint inhibitor. Patients have gone through chemotherapy, and the disease is under control. But instead of waiting for disease to progress after chemotherapy—which it will quickly do in patients with advanced urothelial cancer—adding avelumab significantly improved survival,” he continued.

Patients with advanced urothelial cancer who respond to first-line platinum-based chemotherapy typically relapse eventually, and theoretically, maintenance therapy can prolong progression-free survival. JAVELIN Bladder 100 is the first maintenance trial to show a survival advantage in patients with advanced urothelial cancer with stable disease or better after first-line chemotherapy.

Avelumab is a PD-L1 inhibitor approved for the treatment of advanced urothelial cancer that has progressed on platinum-based chemotherapy. The immune checkpoint inhibitor is also approved for renal cell carcinoma and Merkel cell carcinoma.

Study Details

JAVELIN Bladder 100 is a randomized phase III trial that enrolled patients with unresectable locally advanced or metastatic urothelial cancer without disease progression who had a response or stable disease after being treated in the first line with four to six cycles of gemcitabine/cisplatin or gemcitabine/carboplatin. Patients were randomly assigned 1:1 to receive maintenance avelumab at 10 mg/kg intravenously every 2 weeks plus best supportive care vs best supportive care alone. Treatment was continued until disease progression, toxicity, or death.

The primary endpoint was overall survival in all 700 randomly assigned patients and in 358 patients (51%) with PD-L1–positive tumors according to the Ventana SP263 assay. Results were stratified according to best response to first-line chemotherapy (complete response, partial response, or stable disease) and by visceral vs nonvisceral disease at the time of initiating first-line chemotherapy.


On June 30, 2020, the U.S. Food and Drug Administration approved the supplemental Biologics License Application for avelumab (Bavencio) for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy. Approval was based on results of the Phase III JAVELIN Bladder 100 study.

Patients were followed for 19.6 months in the avelumab group and 19.2 months in the best supportive care–alone group. The combination of avelumab plus best supportive care significantly prolonged overall survival by 31% (P =.001) vs best supportive care alone. The median overall survival was 21.4 months vs 14.3 months, respectively—a 7-month gain.

Among patients with PD-L1–positive tumors, survival was significantly prolonged by 44% (P = .001). In this group, the median overall survival was not reached for avelumab-treated patients vs 17.1 months for the best supportive care–alone group. All prespecified subgroups had an overall survival benefit from avelumab, including age, Eastern Cooperative Oncology Group performance status, first-line chemotherapy regimen, best response to chemotherapy, site of baseline metastasis, creatinine clearance, and PD-L1 status.

Adverse events of any grade occurred in 98% of avelumab recipients vs 77% in the best supportive care–alone group. Grade 3 or higher events—most frequently urinary tract infection, anemia, hematuria, fatigue, and back pain—were reported in 47.4% vs 25.2%, respectively. 

DISCLOSURE: The study was funded by Pfizer as part of an alliance between Pfizer and Merck KGaA, Darmstadt, Germany. Dr. Powles has received honoraria from AstraZeneca, Bristol-Myers Squibb, Ferring, GLG Group, Janssen, Merck, Novartis, Pfizer, Roche/Genentech, and Seattle Genetics/Astellas; has served in a consulting or advisory role for AstraZeneca, Bristol-Myers Squibb, Genentech/Roche, Incyte, Ipsen, Merck, Novartis, Pfizer, and Seattle Genetics; has received research funding from AstraZeneca/MedImmune and Roche/Genentech; and has been reimbursed for travel, accommodations, or other expenses by AstraZeneca, Bristol-Myers Squibb, Ferring, MSD, Novartis/Ipsen, Pfizer, Research to Practice, and Roche/Genentech.


1. Powles T, et al: Maintenance avelumab + best supportive care (BSC) vs BSC alone after platinum-based first-line chemotherapy in advanced urothelial carcinoma. ASCO20 Virtual Scientific Program. Abstract LBA1.


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