Nivolumab as adjuvant therapy

Abstract

Patients undergoing radical cystectomy for muscle-invasive urothelial carcinoma have a high risk of disease recurrence, indicating a need for adjuvant therapy. Cisplatin-based chemotherapy is effective in patients who have not received neoadjuvant platinumbased chemotherapy, although, thus far, no therapies have been shown to improve outcomes in patients who are either ineligible for, or had residual disease after, neoadjuvant chemotherapy. Now, data from a phase iii trial demonstrate the efficacy of the anti-PD-1 antibody nivolumab in this setting. a total of 709 patients with carcinomas originating from the bladder, renal pelvis or ureter, and with pathological evidence of a high risk of disease recurrence after radical cystectomy, were randomly assigned (1:1) to receive either adjuvant nivolumab or placebo. all patients either refused or were ineligible for cisplatin-based chemotherapy. Disease-free survival (DFs) in the intentionto-treat (itt) and tumour PD-L1 ≥ 1% populations were the co-primary end points. after a median follow-up duration of 20.9 months in the nivolumab group and 19.5 months in the placebo group, median DFs durations in the itt population were 20.8 months versus 10.8 months. in the itt and PD-L1 ≥ 1% populations, 6-month DFs was 74.9% versus 60.3% (Hr 0.70, 98.22% Ci 0.55–0.90; P < 0.001) and 74.5% versus 55.7% (Hr 0.55, 98.72% Ci 0.35–0.85; P < 0.001), respectively. Distant metastasis-free survival (in the itt population) was also improved with nivolumab (40.5 months versus 29.5 months). treatment-related adverse events (traes) occurred in 77.5% of patients receiving nivolumab versus 55.5% receiving placebo. Of these, 17.9% versus 7.2% of patients had one or more grade ≥3 traes, most notably including elevated serum levels of lipase (5.1%) and amylase (3.7%). these findings support the use of nivolumab as an effective adjuvant therapy for patients undergoing radical cystectomy who are unable or unwilling to receive cisplatin-based chemotherapy. whether adjuvant nivolumab provides better outcomes than neoadjuvant use, or combined use in both settings, remains to be determined. Peter Sidaway