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Perioperative Durvalumab for Muscle-Invasive Bladder Cancer?
Cisplatin-based neoadjuvant chemotherapy can modestly improve overall survival (OS) in patients with muscle-invasive bladder cancer undergoing radical cystectomy. Recently, two adjuvant immune checkpoint studies demonstrated improvement in disease-free survival (NEJM JW Oncol Hematol Jun 2 2021 and N Engl J Med 2021 Jun 3; 384:2102; N Engl J Med 2024 Sep 14; [e-pub]).
In an industry-sponsored, international, open-label trial, 1063 patients were randomized to undergo radical cystectomy preceded by neoadjuvant gemcitabine-cisplatin (GC) for 4 cycles either with or without durvalumab (4 neoadjuvant cycles followed by 8 adjuvant cycles every 4 weeks). Of note, patients with T2N0 disease were limited to 40% of the patient population, and those with a creatinine clearance of 40–60 mL/minute/1.73 m2 were limited to 20% (the latter were managed with split-course cisplatin dosing).
Among the key findings:
- Pathologic complete response, one of two primary endpoints, did not differ significantly between the durvalumab arm and the GC-alone arm (34% vs. 26%).
- Estimated event-free survival at 24 months, the other primary endpoint, was significantly higher in the durvalumab arm than the GC-alone arm (68% vs. 60%).
- Estimated OS at 24 months was significantly higher in the durvalumab arm (82% vs. 75%).
- Grade 3 or 4 adverse events occurred with similar frequency in the two arms.
Comment
For cisplatin-eligible patients fit to undergo radical cystectomy, the combination of durvalumab plus GC represents a new standard of care. It is important to remember that carboplatin and cisplatin are not interchangeable agents in urothelial cancer, and thus extrapolating this experience to durvalumab-gemcitabine plus carboplatin is inappropriate. Treating patients with creatine clearance between 40 and 60 mL/minute requires experience and vigorous patient oversight. Notably, adjuvant immune-checkpoint therapy was not incorporated in the chemotherapy-only arm. Other perioperative trials, including one exploring the role of enfortumab vedotin/pembrolizumab, may provide options for patients who are not candidates for cisplatin.
Citation(s)
Author:
Powles T et al.
Title:
Perioperative durvalumab with neoadjuvant chemotherapy in operable bladder cancer.
Source:
N Engl J Med
2024
Sep
15; [e-pub].
(Abstract/FREE Full Text)
Empfohlen von
Robert Dreicer, MD, MS, MACP, FASCO