Interim analysis of the phase 3 JAVELIN Bladder 100 clinical trial showed that maintenance therapy with the PD-L1 inhibitor avelumab (Bavencio) plus best supportive care significantly prolonged overall survival (OS) versus best supportive care alone in patients with advanced urothelial carcinoma whose disease did not progress with first-line platinum-based chemotherapy. The survival benefit extended to all patients enrolled in the study, regardless of PD-L1 expression status and in all prespecified subgroups.
The JAVELIN Bladder 100 is the first maintenance clinical trial to show a survival advantage in patients with advanced urothelial cancer with stable disease or better after first-line chemotherapy, according to Thomas Powles, MD, PhD, MRCP, FCRP, Lead for Solid Oncology, Barts Cancer Institute, London, England, who presented these results at the plenary session of the ASCO 2020 virtual annual meeting.
“This study met its primary objective, demonstrating significantly prolonged overall survival with first-line maintenance avelumab and best supportive care versus best supportive care alone in the overall population and in PD-L1–positive patients whose disease did not progress on platinum-based chemotherapy,” Dr Powles said. “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.”
The randomized, prospective, phase 3 JAVELIN Bladder 100 trial enrolled patients with unresectable locally advanced or metastatic urothelial cancer without disease progression after response or stable disease after 4 to 6 cycles of first-line gemcitabine-cisplatin or gemcitabine-carboplatin.
A total of 700 patients were randomized in a 1:1 ratio to maintenance avelumab 10 mg/kg intravenously every 2 weeks plus best supportive care versus best supportive care alone. Treatment was continued until disease progression, unacceptable toxicity, or death. Of the 700 patients, 358 (51%) had PD-L1 expression. The median follow-up was 19.6 months in the avelumab group and 19.2 months in the best supportive care group.
Maintenance therapy with avelumab plus best supportive care prolonged the OS by 31% (P = .001) versus best supportive care alone. The median OS was 21.4 months versus 14.3 months, respectively, a 7-month gain.
In patients whose tumor expressed PD-L1, avelumab significantly prolonged survival versus best supportive care alone by 44% (P = .001). The median OS was not reached in patients who received avelumab versus 17.1 months in patients who received best supportive care alone.
In a prespecified subgroup analysis, the addition of avelumab resulted in an OS benefit across the board, regardless of 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.
The median progression-free survival in the overall population was 3.7 months for the avelumab-based group versus 2 months for best supportive care group alone.
Adverse events of any grade were reported in 98% of those who received avelumab versus 77.1% in those who received best supportive care alone; grade ≥3 adverse events were reported in 47.4% versus 25.2%, respectively.
Crossover to avelumab is allowed in the trial, and follow-up will continue.