Interim analysis of the phase 3 JAVELIN Bladder 100 trial showed that maintenance therapy with the PD-L1 inhibitor Bavencio (avelumab) plus best supportive care significantly prolonged survival compared with the current best supportive care alone in patients with advanced urothelial carcinoma, the most common type of bladder cancer, that did not progress (get worse) after treatment with first-line platinum-based chemotherapy.
This survival benefit was seen in all patients who participated in the clinical trial, regardless of the PD-L1 status of their tumor, and in all other subgroups of the study.
PD-L1 expression is a biomarker found on some tumors that can affect the tumor’s response to therapy. The targeted drugs known as PD-L1 inhibitors, such as avelumab, are specifically designed to target and kill cancer cells that express PD-L1, thereby improving the response to therapy and extending patients’ survival.
JAVELIN Bladder 100 Trial
These results were presented at the 2020 ASCO annual meeting by Thomas Powles, MD, PhD, MBBS, MRCP, FCRP, Lead for Solid Oncology, Experimental Cancer Medicine Centre, Barts Cancer Institute, London, England. JAVELIN Bladder 100 is the first study of maintenance therapy in bladder cancer to show a survival advantage in patients with advanced bladder cancer whose disease is stable after first-line chemotherapy.
“This study met its primary objective, demonstrating significantly prolonged overall survival with first-line maintenance avelumab [Bavencio] 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,” he emphasized.
JAVELIN Bladder 100 was a randomized, prospective, phase 3 clinical trial that enrolled patients with unresectable (cannot be removed surgically) locally advanced or metastatic (spreading) urothelial cancer whose disease did not progress after receiving 4 to 6 cycles of first-line gemcitabine plus cisplatin or gemcitabine plus carboplatin.
The study evaluated the benefit of avelumab as maintenance therapy in patients who responded to platinum-based chemotherapy. A total of 700 patients were randomized (divided into groups) to receive maintenance avelumab intravenously every 2 weeks plus best supportive care versus best supportive care alone. The treatment was continued until disease progression, unacceptable side effects, or death. Of the 700 patients, more than half (358) had PD-L1 expression on their tumor.
The average follow-up of patients was 19.6 months in the avelumab group and 19.2 months in the best supportive care group. The combination of avelumab plus best supportive care significantly prolonged patient survival by 31% compared with best supportive care alone. The average overall survival was 21.4 months with avelumab versus 14.3 months with best supportive care alone, a 7-month gain in survival.
Longer Survival with Avelumab
In the patients who had PD-L1 expression on their tumor, treatment with avelumab significantly prolonged survival compared with supportive care alone by 44%. The average overall survival was not reached for patients in the avelumab group (meaning patients are still alive) compared with 17.1 months for the patients who received supportive care alone.
In a prespecified subgroup analysis, avelumab achieved an overall survival benefit across all patient characteristics, including age, overall performance status, which first-line chemotherapy regimen was used, site of baseline metastasis, and PD-L1 status.
The average progression-free survival in the overall population was 3.7 months with avelumab and 2 months with supportive care alone.
Side effects of any grade or severity were reported in most (98%) of the patients who received avelumab compared with 77.1% in the patients who received best supportive care alone.
Serious (grade 3 or 4) side effects were reported in 47.4% of the patients who received avelumab versus 25.2% of patients who received supportive care alone.
Patients are allowed to cross over from the supportive care to the avelumab group, as patients are still receiving therapy and are being followed up for longer results.
- PD-L1 expression is a biomarker found on some tumors that can affect the tumor’s response to therapy
- PD-L1 inhibitors, such as avelumab, are designed to target and kill cancer cells that express PD-L1, thereby improving the response to therapy and extending survival
- Maintenance therapy with the PD-L1 inhibitor avelumab plus supportive care extended survival in patients with advanced urothelial carcinoma versus supportive care alone
- Avelumab as first-line maintenance is a new standard of care for patients with advanced bladder cancer that has not progressed with platinum-based chemotherapy