Results of a multicenter, phase 2 study of nivolumab and ipilimumab for patients with advanced rare genitourinary malignancies
Mené sur 55 patients atteints d'un cancer génito-urinaire rare et de stade avancé, cet essai multicentrique de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un traitement combinant nivolumab et ipilimumab (durée médiane de suivi : 9,9 mois)
Background : In this multicenter, single‐arm, multicohort, phase 2 trial, the efficacy of nivolumab and ipilimumab was evaluated in patients with advanced rare genitourinary cancers, including bladder and upper tract carcinoma of variant histology (BUTCVH), adrenal tumors, platinum‐refractory germ cell tumors, penile carcinoma, and prostate cancer of variant histology (NCT03333616). Methods : Patients with rare genitourinary malignancies and no prior immune checkpoint inhibitor exposure were enrolled. Patients received nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg intravenously every 3 weeks for 4 doses, and this was followed by 480 mg of nivolumab intravenously every 4 weeks. The primary endpoint was the objective response rate (ORR) by the Response Evaluation Criteria in Solid Tumors (version 1.1). Results : Fifty‐five patients were enrolled at 6 institutions between April 2018 and July 2019 in 3 cohorts: BUTCVH (n = 19), adrenal tumors (n = 18), and other tumors (n = 18). The median follow‐up was 9.9 months (range, 1 to 21 months). Twenty‐eight patients (51%) received 4 doses of nivolumab and ipilimumab; 25 patients received nivolumab maintenance for a median of 4 cycles (range, 1‐18 cycles). The ORR for the entire study was 16% (80% confidence interval, 10%‐25%); the ORR in the BUTCVH cohort, including 2 complete responses, was 37%, and it was 6% in the other 2 cohorts. Twenty‐two patients (40%) developed treatment‐related grade 3 or higher toxicities; 24% (n = 13) required high‐dose steroids (≥40 mg of prednisone or the equivalent). Grade 5 events occurred in 3 patients; 1 death was treatment related. Conclusions : Nivolumab and ipilimumab resulted in objective responses in a subset of patients with rare genitourinary malignancies, especially those with BUTCVH. An additional cohort exploring their activity in genitourinary tumors with neuroendocrine differentiation is ongoing.
Cancer 2020