Clinical Outcomes of Patients with MIBC Treated with Adjuvant Nivolumab - Expert Commentary
The investigators reviewed the records of 253 patients with clinical stage II-IIIB muscle-invasive urothelial carcinoma who initiated adjuvant nivolumab between September 2021 and November 2022. The median follow-up was 12.8 (9.6-15.4) months. Median age at diagnosis was 67.8 (61.5-72.4) years, with 169 patients (66.8%) male. The study population was more diverse than CheckMate 274, including 62 Black or African American patients (24.5%) and 45 patients (18.0%) with ECOG performance status ≥2.
Overall, 141 patients (55.7%) received neoadjuvant chemotherapy, predominantly gemcitabine plus cisplatin (119 patients, 84.4%). Among 112 patients who did not receive neoadjuvant chemotherapy, 88 (78.6%) were cisplatin-ineligible, primarily due to creatinine clearance <60 mL/min (79 patients, 70.5%). Most patients initiated nivolumab at 480 mg every 4 weeks (175 patients, 69.2%). The median treatment duration was 11.2 (8.4-12.0) months, with 220 patients (87.0%) discontinuing therapy primarily due to completion of scheduled duration (163 patients, 74.1%).
Survival outcomes were favorable, with median disease-free survival and overall survival not reached. Twelve-month disease-free survival was 86.3% (95% CI, 81.0%-90.2%), and 12-month overall survival was 90.8% (95% CI, 86.0%-94.0%). Patients who received neoadjuvant chemotherapy had 12-month disease-free survival of 90.0% (95% CI, 82.9%-94.3%) and overall survival of 95.6% (95% CI, 89.6%-98.2%). Among patients who did not receive neoadjuvant chemotherapy, 12-month disease-free survival was 81.6% (95% CI, 72.6%-87.9%) and overall survival was 85.0% (95% CI, 76.3%-90.7%). Adverse events occurred in 52 patients (20.6%), with diarrhea (18 patients, 7.1%) and hypothyroidism (15 patients, 5.9%) most common. Only 10 patients (4.5%) discontinued treatment due to adverse events. Recurrence occurred in 26 patients (10.3%), predominantly distant metastases (25 patients). At last follow-up, 226 patients (89.3%) were alive, with 209 (92.5%) disease-free.
This important study demonstrated clinical outcomes consistent with the CheckMate 274 trial, even with a more diverse population with worse performance status. These results support efficacy of adjuvant nivolumab use in patients who did not receive neoadjuvant chemotherapy, addressing a key clinical question from the original trial. Study limitations include potential selection bias, lack of standardized surveillance protocols, and absence of central imaging review. Extended follow-up is needed to assess long-term clinical outcomes.
Written by: Bishoy M. Faltas, MD, Chief Research Officer, Englander Institute for Precision Medicine, Gellert Family - John P. Leonard, MD, Research Scholar, Associate Professor of Medicine, Cell and Developmental Biology, Weill Cornell Medicine, New York- Presbyterian Hospital, NY
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