Bavencio Soon After Chemotherapy Improves Survival in Patients with Advanced Bladder Cancer

The immunotherapy Bavencio (avelumab), given shortly after initial chemotherapy for advanced urothelial carcinoma, significantly extends survival, according to a study whose results were reported during the virtual scientific program of the American Society of Clinical Oncology (ASCO) Annual Meeting.

Researchers reported that Bavencio improved survival by 7.1 months in patients with inoperable locally advanced or metastatic urothelial cancer who had experienced no disease progression after taking chemotherapy as an initial treatment. In the study, patients got best supportive care — meaning the management of their disease-related symptoms — with or without Bavencio. The immunotherapy was given as a maintenance treatment, intended to sustain the response to chemotherapy and help delay or prevent cancer’s recurrence.

Urothelial carcinoma is the most common type of bladder cancer. Bavencio is an immunotherapy known as a checkpoint inhibitor that interferes with a protein used by cancer to hide from the immune system. By disabling that protein, the drug makes the cancer more visible to the immune system, which can then work to fight it.

The results from the phase 3 JAVELIN Bladder 100 trial represent the largest survival benefit seen to date in advanced urothelial cancer in the maintenance setting, and the first showing efficacy of Bavencio just after initial chemotherapy, a time when recurrence frequently occurs, ASCO stated in a press release.

The findings were strong enough to suggest that this treatment should be the new standard after chemotherapy in these patients, said the study’s lead author, Dr. Thomas Powles, a professor of genitourinary oncology and director of Barts Cancer Centre in London.

Powles noted that Bavencio and other checkpoint inhibitors are already available to patients with this disease whose cancer progresses after platinum-based chemotherapy, but he said that only 22% to 55% of eligible patients receive it, with a minority of those patients gaining a durable clinical benefit. The aim of using such drugs as maintenance treatments is to prevent these relapses.

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

The trial included 700 patients with inoperable locally advanced or metastatic urothelial carcinoma who had experienced no disease progression following four to six cycles of chemotherapy: gemcitabine plus either cisplatin or carboplatin. Of the total study population, 350 patients received intravenous Bavencio every two weeks along with BSC, and 350 were assigned to BSC alone. The patients started their study treatment within 10 weeks of completing chemotherapy.

The study’s main goal was to measure length of life, or overall survival (OS), starting from the time patients were assigned to study groups, in two populations: all patients in the study and those whose tumors expressed the cancer-driving protein PD-L1, which is targeted by Bavencio. Also measured were the length of time until disease progression, the proportion of patients who experienced a partial or complete response to treatment and safety.

Researchers also watched for differences in patient health outcomes based on whether they had visceral versus non-visceral disease when they started chemotherapy, and whether they had experienced a complete or partial response to chemotherapy versus stable disease.

Patients were followed for a median 19 months.

Investigators found that Bavencio plus BSC generated a median OS of 21.4 months compared with 14.3 months for BSC alone.

In the 358 patients whose tumors were PD-L1-positive, median OS had not yet been reached in the Bavencio group and was 17.1 months in the BSC-alone group. An OS benefit for Bavencio was seen in all the subgroups studied, although those with visceral disease prior to chemotherapy had worse outcomes than those who started with non-visceral disease.Time until disease progression was 38% better in the Bavencio arm compared with the BSC-alone group across all study patients (3.7 vs 2.0 months, respectively) and was 44% improved in the Bavencio group compared with the BSC-alone group in patients with PD-L1-positive tumors.

“In urothelial cancer, patients have high PD-L1 expression and high tumor mutation burden. Response rates associated with immune therapy are pretty high,” Powles said. “This means that checkpoint inhibitors can work quite well in urothelial cancer.”

Serious side effects occurred in 47.4% of patients who received Bavencio plus BSC compared with 25.2% in those who received BSC alone. The most common serious or worse side effects were urinary tract infection, anemia, blood in the urine, fatigue and back pain. The safety profile of Bavencio was consistent with previous studies of the drug when given by itself, the authors stated.

The researchers plan to continue to follow patients to see how long the response is maintained.

The study was funded by Pfizer (Merck KgA).