Results of a multicenter, phase 2 study of nivolumab and ipilimumab for patients with advanced rare genitourinary malignancies.

Publisher: Wiley Country of Publication: United States NLM ID: 0374236 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-0142 (Electronic) Linking ISSN: 0008543X NLM ISO Abbreviation: Cancer Subsets: MEDLINE

Publication: <2005- >: Hoboken, NJ : Wiley
Original Publication: New York [etc.] Published for the American Cancer Society by J. Wiley [etc.]

Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Ipilimumab/*administration & dosage ; Nivolumab/*administration & dosage ; Urogenital Neoplasms/*drug therapy; Female ; Humans ; Ipilimumab/adverse effects ; Male ; Middle Aged ; Nivolumab/adverse effects ; Rare Diseases ; Urogenital Neoplasms/mortality

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.
Lay Summary: Patients with rare cancers are often excluded from studies and have limited treatment options. Fifty-five patients with rare tumors of the genitourinary system were enrolled from multiple sites and were treated with nivolumab and ipilimumab, a regimen used for kidney cancer. The regimen showed activity in some patients, particularly those with bladder or upper tract cancers of unusual or variant histology; 37% of those patients responded to therapy. Additional studies are ongoing to better determine who benefits the most from this combination.
(© 2020 American Cancer Society.)

Comment in: Nat Rev Urol. 2021 Mar;18(3):133-134. (PMID: 33432180)

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Bristol-Myers Squibb; P30 CA016672 United States NH NIH HHS

Keywords: adrenal tumor; bladder or upper tract tumor of variant histology; genitourinary; immunotherapy; rare cancer

ClinicalTrials.gov NCT03333616

0 (Ipilimumab)
31YO63LBSN (Nivolumab)

Date Created: 20201120 Date Completed: 20211014 Latest Revision: 20211014

20240829

10.1002/cncr.33328

33216356