Dr Apolo on Adjuvant Pembrolizumab in Muscle-Invasive Urothelial Carcinoma

Andrea B. Apolo, MD, senior investigator, head, Bladder Cancer Section, Genitourinary Malignancies Branch, director, Bladder Cancer and Genitourinary Tumors Multidisciplinary Clinic, National Institutes of Health, discusses interim findings from the phase 3 AMBASSADOR Alliance A031501 trial (NCT03244384) of adjuvant pembrolizumab (Keytruda) vs observation in patients with locally advanced and muscle-invasive urothelial carcinoma.

The open-label, randomized AMBASSADOR trial enrolled patients with histologically confirmed muscle-invasive bladder, upper tract, or urethral cancer who had pN+ and/or pT2 margins+ at surgery following neoadjuvant chemotherapy or pN+ and/or pT3 positive margins at surgery and were either ineligible for cisplatin or declined adjuvant cisplatin-based therapy. Surgery included nephrectomy, radical cystectomy, ureterectomy, or nephroureterectomy. Patients were randomly assigned in a 1:1 ratio to receive either pembrolizumab at 200 mg every 3 weeks for 1 year or undergo observation. Disease-free survival (DFS) and overall survival (OS) served as the dual primary end points of the trial; secondary objectives included DFS and OS in PD-L1–positive and –negative patients, as well as safety.

This trial met one of its dual primary end points of DFS, Apolo says. At a median follow-up of 22.3 months (range, 0.03-48.9), the median DFS with adjuvant pembrolizumab was 29.0 months (95% CI, 21.8-not reached [NR]) vs 14.0 months (95% CI, 9.7-20.2) with observation (HR, 0.69; 95% CI, 0.54-0.87; P = .001). At a median follow-up of 36.9 months (range, 0-63.9), the median OS was 50.9 months (95% CI, 43.9-NR) with pembrolizumab vs 55.8 months (95% CI, 53.3-NR) with observation.

The AMBASSADOR Alliance A031501 trial investigators also performed PD-L1 testing to determine whether PD-L1 status was predictive of benefit with adjuvant pembrolizumab, Apolo adds. Although the patients with PD-L1–positive disease had a better prognosis than those with PD-L1–negative disease, PD-L1 was not found to be predictive of outcomes with adjuvant pembrolizumab, Apolo explains.

Adjuvant nivolumab (Opdivo) is currently FDA approved for patients with high-risk urothelial carcinoma. The findings from the AMBASSADOR Alliance A031501 trial support the use of adjuvant pembrolizumab as an additional treatment option for patients with muscle-invasive disease, Apolo concludes.