Introduction and objectives: One year of durvalumab (D) plus BCG induction (I) + maintenance (M) vs BCG (I+M) alone demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) in patients (pts) with BCG-naïve, high-risk non-muscle-invasive bladder cancer (NMIBC; POTOMAC, NCT03528694). Early recurrence is associated with worse outcomes and BCG unresponsive disease is an indication for radical cystectomy. Papillary tumors constitute the majority of NMIBC, and their prognosis depends on disease stage and grade. This was also the largest pt subgroup in POTOMAC. We report in-depth additional efficacy and safety analyses for D+BCG (I+M) vs BCG (I+M).
Methods: Eligible pts who had TURBT (complete resection; including residual carcinoma in situ [CIS]) were randomized 1:1:1 to D+BCG (I+M), D+BCG (I), or BCG (I+M). For D+BCG (I+M) vs BCG (I+M), we report time to cystectomy (secondary endpoint) and post-hoc exploratory analyses of time to high-risk disease event, BCG-unresponsive disease per FDA guidelines, median time to cystectomy, cystectomy-free survival (time from randomization to cystectomy/death), and outcomes in pts with papillary tumors.
Results: Fewer high-risk disease events (high-risk NMIBC recurrence [high-grade Ta/T1/CIS], persistent CIS at 6 mo, or MIBC/metastasis) occurred with D+BCG (I+M) (53/339) vs BCG (I+M) (69/340). Median time to high-risk event was 14.1 vs 8.3 mo; 45% (24/53) vs 61% (42/69) of pts had early high-risk events (≤1 year from randomization). At recurrence, 65% (24/37; D+BCG [I+M]) vs 81% (44/54; BCG [I+M]) met BCG-unresponsive criteria. Time to cystectomy in ITT resulted in a HR of 0.63 (95% CI 0.31–1.24) with D+BCG (I+M) vs BCG (I+M), with medians not reached in either arm. Among pts who underwent cystectomy, median time to cystectomy was 19.0 vs 14.1 mo. The cystectomy-free survival HR was 0.69 (95% CI 0.48–0.99) with D+BCG (I+M) vs BCG (I+M). Outcomes in papillary subgroups are summarised (Table). Safety in pts with papillary tumors was consistent with the overall population.
Conclusions: Fewer early high-risk events occurred with D+BCG (I+M) vs BCG (I+M), as well as a delayed time to high-risk events, and fewer BCG-unresponsive recurrences. Time to cystectomy and cystectomy-free survival showed a trend in favor of D+BCG (I+M) vs BCG (I+M). Notably, a DFS benefit was observed across papillary subgroups with D+BCG (I+M). These data further support D+BCG (I+M) as a potential new treatment in this setting.
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Source of Funding: AstraZeneca