Front-line Bavencio Maintenance Improves Survival Regardless of Primary Tumor Site, Advanced Disease Type in Advanced Bladder Cancer

Bavencio (avelumab) as front-line maintenance plus best supportive care demonstrated a survival benefit compared with best supportive care alone in patients with advanced urothelial cancer who have progressed on first-line platinum-containing chemotherapy, according to findings from an analysis of a phase 3 trial.

Findings from this analysis were presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

The progression-free survival and overall survival improvements were seen in patients with upper tract or lower tract disease; metastatic disease, unresectable locally advanced disease, or lymph node–only disease; PD-L1–positive tumors who received frontline gemcitabine/carboplatin and tumor genomic subtypes, with the exception of those with the luminal subtype.

Additionally, an analysis of important immune biomarkers by subtype did not predict benefit with Bavencio in the frontline maintenance setting.

“Overall, it doesn’t appear that this molecular … analysis is able to identify the ‘winners and the losers’ associated with maintenance (Bavencio). This is important because it means we need to move to different types of biomarkers in the future,” lead study author Dr. Thomas Powles, a professor of genitourinary oncology and director of Barts Cancer Centre in London, United Kingdom, said in a presentation during the meeting. “We’ve added something to the field today. I believe that biomarker-positive (and) carboplatin subgroups of patients are relevant, and I also think that the molecular analysis builds on what we know and points us in a different direction of biomarker development in the future.”

In the trial, patients with locally advanced or metastatic urothelial cancer that had not progressed on front-line chemotherapy received front-line maintenance with Bavencio plus best supportive care (350 patients) or best supportive care alone (350 patients) until disease progression, unacceptable toxicity or withdrawal from the trial.

Factors that researchers focused on throughout the trial included overall survival in the overall study population and in those with PD-L1–positive tumors, in addition to effects from the treatment based on a patient’s tumor site and type of advanced disease.

The progression-free survival and overall survival benefits were observed irrespective of primary tumor site or type of advanced disease. There was, however, a greater difference of overall survival outcomes in those with lower tract primary tumors, unresectable locally advanced disease or lymph node–only disease following chemotherapy, but the investigators noted that the number of patients and events were small.

The progression-free survival outcomes were similar with Bavencio/best supportive care versus best supportive care alone in these exploratory subgroups: lower tract, locally advanced and unresectable disease and lymph node–only disease. Similar to the overall survival data, the luminal subtype showed the least benefit of the other key immune biomarker subtypes.

In the basal squamous subgroup, the median overall survival was 24 months and 17.9 months with Bavencio/best supportive care (46 patients) and best supportive care alone (44 patients), respectively. In the luminal subgroup, the median overall survival was 23.8 months (30 patients) and not evaluable (26 patients), respectively.

In the luminal-infiltrated group, the median overall survival was 19.9 months with Bavencio/best supportive care (143 patients) and 14.3 months with best supportive care alone (143 patients). Finally, in the luminal papillary subgroup, the median overall survival was 22.5 months with Bavencio/best supportive care (61 patients) compared with 13.4 months with best supportive care alone (63 patients).

Further data showed that longer outcomes were seen in the Bavencio group in patients with PD-L1–positive disease who received front-line gemcitabine/carboplatin for progression-free survival and overall survival. These data were consistent with the overall study population.

Specifically, the median overall survival was 24 months with Bavencio plus best supportive care and 16.1 months with best supportive care alone; the median progression-free survival was 3.7 months and 2.4 months, respectively.

“These data really support further the approach of giving chemotherapy to get control of the disease and then maintaining that control with maintenance (Bavencio) rather than giving front-line immune therapy, in my opinion, and I think this does really add to the field,” Powles said.

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