Dr Galsky on the Significance of the FDA Approval of Perioperative Durvalumab Plus Gemcitabine/Cisplatin for MIBC

"The significance of the approval of perioperative durvalumab for the treatment of patients with MIBC is that it really represents the first time that a treatment has been added to standard cisplatin-based chemotherapy in the neoadjuvant setting, which has improved outcomes."

Matthew Galsky, MD, a professor of medicine (hematology and medical oncology) and urology at the Icahn School of Medicine at Mount Sinai; as well as the director of genitourinary medical oncology co-director of the Center of Excellence for Bladder Cancer, and associate director for Translational Research at The Tisch Cancer Institute, discussed the clinical implications of the FDA approval of perioperative durvalumab (Imfinzi) in combination with gemcitabine and cisplatin as neoadjuvant therapy for patients with muscle-invasive bladder cancer (MIBC).

The regulatory decision was based on data from the phase 3 NIAGARA trial (NCT03732677), in which patients were randomly assigned to receive neoadjuvant durvalumab plus gemcitabine and cisplatin followed by single-agent durvalumab after radical cystectomy, or neoadjuvant gemcitabine plus cisplatin followed by radical cystectomy alone. The regimen resulted in a statistically significant improvement in event-free survival (EFS)—the trial’s primary endpoint—with a HR of 0.68 (95% CI, 0.56-0.82; 2-sided P < .0001). The median EFS was not reached (NR; 95% CI, NR-NR) in the experimental arm compared with 46.1 months (95% CI, 32.2-NR) in the chemotherapy-only arm. The benefit with the experimental regimen regarding overall survival (OS)—a key secondary end point—was also statistically significant (HR, 0.75; 95% CI, 0.59-0.93; 2-sided P = .0106); the median OS was NR in either arm.

Galsky noted that this approval marks a meaningful advancement in the MIBC neoadjuvant treatment paradigm, representing the first time since the initial approval of neoadjuvant cisplatin-based chemotherapy that a therapeutic addition has demonstrated improved outcomes in this population. The improvement in pathological complete response (pCR), which was 9.8% higher in the durvalumab arm, further supports the clinical benefit of the regimen.

The safety profile of perioperative durvalumab in combination with chemotherapy was consistent with those seen in prior reports, Galsky added, with no unexpected safety signals observed. Immune-related adverse effects were manageable and aligned with established experience using checkpoint inhibition in patients with urothelial carcinoma.

Galsky emphasized that the incorporation of perioperative durvalumab into the standard treatment algorithm for cisplatin-eligible patients with MIBC reflects a step forward in the optimization of multimodality therapy. As new data continue to emerge, refinement of patient selection strategies and identification of biomarkers will be essential to maximizing the therapeutic potential of immune checkpoint blockade in earlier stages of urothelial cancer, he concluded.