Durvalumab (Imfinzi) plus BCG induction and maintenance improved disease-free survival (DFS) vs BCG induction and maintenance alone in patients with BCG-naive, high-risk, papillary-only
At a median follow-up of 60.7 months, DFS events occurred in 17% of patients with papillary-only tumors in the durvalumab plus BCG arm (n = 217) vs 30% of those in the BCG-alone arm (n = 220; HR, 0.56; 95% CI, 0.37-0.84); median DFS was not reached (NR) in either arm. The 48-month DFS rates were 84% vs 74%, respectively.
In the T1 subset of the papillary-only population, DFS events occurred in 16% of patients in the durvalumab arm (n = 137) vs 31% in the BCG-alone arm (n = 145; HR, 0.48; 95% CI, 0.28-0.79), with 48-month DFS rates of 85% vs 73%.
"These findings further support 1 year of durvalumab in combination with BCG induction and maintenance as a new treatment option for BCG-naive, high-risk NMIBC, including those patients with papillary-only tumors," said lead study author Maria De Santis, MD, of Charité Universitätsmedizin Berlin in Germany and the Medical University of Vienna in Austria, in a presentation of the data.
POTOMAC randomly assigned 1018 patients with BCG-naive, high-risk NMIBC 1:1:1 to durvalumab at 1500 mg intravenously every 4 weeks for 13 cycles plus BCG induction (weekly for 6 weeks) and maintenance (3 weekly doses at 3, 6, 12, 18, and 24 months); durvalumab plus BCG induction only; or BCG induction and maintenance alone. The primary end point was investigator-assessed DFS for durvalumab plus BCG induction and maintenance vs BCG induction and maintenance alone in the intention-to-treat population.
In the final analysis, published in The Lancet, the combination met its primary end point (HR, 0.68; 95% CI, 0.50-0.93; P = .015).2 The current analysis included patients with papillary-only tumors, defined as T1 or Ta disease without carcinoma in situ that met high-risk enrollment criteria, who made up 64% to 65% of the intention-to-treat population.
The papillary-only analysis was prespecified, and the T1 analysis was post hoc.1 Median age was 67 years in both arms; T1 disease accounted for 63% and 66% of patients, respectively, and 53% and 55% had higher-risk papillary disease.
In the papillary-only population, high-risk disease recurrence occurred in 13% of patients in the durvalumab arm vs 20% in the BCG-alone arm, including high-risk NMIBC recurrence in 8% vs 15% and muscle-invasive or metastatic disease in 5% of each arm.
Early high-risk events, those within 12 months of randomization, occurred in 16 vs 29 patients, respectively, and in 10 vs 20 patients in the T1 subset.
Among patients with a high-risk NMIBC recurrence, 61.1% of those in the durvalumab arm (n = 18) vs 88.2% of those in the BCG-alone arm (n = 34) met BCG-unresponsive criteria; in the T1 subset, the rates were 60.0% (n = 10) vs 87.5% (n = 24). The
Cystectomies were performed in 3% of patients with papillary-only tumors in the durvalumab arm vs 5% in the BCG-alone arm, and in 3% vs 6% of those with T1 disease.1 Cystectomy-free survival favored durvalumab plus BCG in the papillary-only population (HR, 0.59; 95% CI, 0.38-0.92) and the T1 subset (HR, 0.45; 95% CI, 0.25-0.78).
In the papillary-only safety population, adverse effects (AEs) of any cause occurred in 97% of patients in the durvalumab arm (n = 215) vs 88% in the BCG-alone arm (n = 219). Grade 3 or 4 AEs occurred in 34% vs 16%, treatment-related grade 3 or 4 AEs in 23% vs 3%, and serious AEs in 30% vs 17%. AEs led to treatment discontinuation in 29% vs 17%, and no AEs leading to death were considered treatment related.
Immune-mediated AEs occurred in 27% of patients in the durvalumab arm and were grade 3 or 4 in 9%; the most common were hypothyroid events (11%) and hepatic events (7%). At the data cutoff, 60% of patients with immune-mediated AEs had events that were resolved, resolving, or resolved with sequelae.
Disclosures: De Santis reported receiving consulting fees from AAA, Amgen, Astellas, AstraZeneca, Basilea, Bayer, Bioclin, Bristol Myers Squibb, Eisai, Ferring, Gilead Sciences, Immunomedics, Ipsen, Janssen, Merck Sharp & Dohme, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, Seagen, and Thermosome; receiving honoraria and support for attending meetings and/or travel from AAA, Amgen, Astellas, AstraZeneca, Basilea, Bayer, Bioclin, Bristol Myers Squibb, Eisai, Ferring, Gilead Sciences, Immunomedics, Ipsen, Janssen, Merck Sharp & Dohme, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, and Seagen; participating on safety monitoring or advisory boards for the Thermosome Hyperthermia trial, GUSTO DMEC (academic trial Sheffield, unpaid), and AURORA (academic trial Southampton, unpaid); and holding leadership or fiduciary roles with the ESMO bladder cancer CPG and the German S3 bladder cancer guideline (unpaid).
