Abstract Code: IUC26698-96
Durvalumab + BCG therapy in BCG-naïve, high-risk NMIBC: efficacy and safety analyses from POTOMAC
- Hussain 1, N. Shore 2, H. Nishiyama 3, J. Palou Redorta 4, M. Krawczynski 5, A. Seyitkuliev 6, F. Guerrero-Ramos 7, M. Kato 8, T. Powles 9, M. De Santis 10
(1) Sheffield – United Kingdom, (2) Carolina Urologic Research Center, Mrytle Beach – United States, (3) University of Tsukuba Department of Urology, Tsukaba – Japan, (4) Urology Department at Fundació Puigvert, Barcelona – Spain, (5) KRAWCZYNSKI MEDICAL CENTER, Lodz – Poland, (6) St. Petersburg Research Center of the Russian Academy of Sciences, St.Petersburg – Russian Federation, (7) Hospital Universitario 12 de Octubre, Madrid – Spain, (8) Osaka Metropolitan University Graduate School of Medicine, Osaka – Japan, (9) Barts Cancer Institute, London – United Kingdom, (10) Charité – Universitätsmedizin Berlin, Berlin – Germany
Background: Durvalumab (D) plus BCG induction (I) + maintenance (M) vs BCG (I+M) demonstrated statistically significant, clinically meaningful improvement in disease-free survival (DFS) in patients with BCG-naïve, high-risk non-muscle-invasive bladder cancer (NMIBC; POTOMAC, NCT03528694). We report in-depth efficacy and safety analyses for D+BCG (I+M) vs BCG (I+M).
Methods: Patients were randomized 1:1:1 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 (TTC; secondary endpoint), post-hoc exploratory analyses of time to high-risk event, BCG-unresponsive disease, median TTC, cystectomy-free survival (CFS; time from randomization to cystectomy/death); and outcomes in patients with papillary tumours.
Results: Fewer high-risk disease events with D+BCG (I+M) (53/339) vs BCG (I+M) (69/340). Median time to high-risk event was 14.1 vs 8.3mo; 45% (24/53) vs 61% (42/69) patients had early high-risk events (≤1 year from randomization). At recurrence, 65% (24/37) vs 81% (44/54) met BCG-unresponsive criteria, respectively. TTC had HR 0.63 (95% CI 0.31–1.24) with D+BCG (I+M) vs BCG (I+M), medians not reached in either arm (ITT population); among patients who underwent cystectomy, median TTC was 19.0 vs 14.1mo. CFS favoured D+BCG (I+M) (HR 0.69; 95% CI 0.48–0.99). Efficacy in papillary subgroups is summarised (Table), and safety was consistent with the overall population.
Conclusions: Fewer early high-risk events occurred with D+BCG (I+M) vs BCG (I+M), with delayed time to high-risk events, and fewer BCG-unresponsive recurrences. TTC and CFS favoured D+BCG (I+M) vs BCG (I+M). DFS benefit observed across papillary subgroups with D+BCG (I+M). Funding: AstraZeneca.
D+BCG (I+M) vs BCG (I+M) | DFS | Overall survival | ||
HR (95% CI) | Reduction in risk of disease recurrence, progression or death | HR (95% CI) | Reduction in risk of death | |
Any papillary tumors (91% of ITT) | 0.61 (0.43–0.85) | 39% | 0.76 (0.49–1.16) | 24% |
Papillary only (64−65% of ITT) | 0.56 (0.37–0.84) | 44% | 0.68 (0.42–1.09) | 32% |
Any T1 | 0.55 (0.36–0.83) | 45% | 0.67 (0.39–1.14) | 33% |
T1 only | 0.48 (0.28–0.79) | 52% | 0.52 (0.27–0.93) | 48% |
T1 high grade/grade 3 only | 0.55 (0.31–0.94) | 45% | 0.58 (0.29–1.12) | 42% |
HR <1 favours D+BCG (I+M) vs BCG (I+M).