Details

Autor(en) / Beteiligte

• McGregor, Bradley Alexander
• Campbell, Matthew T.
• Xie, Wanling
• Farah, Subrina
• Bilen, Mehmet A.
• Schmidt, Andrew L.
• Sonpavde, Guru P.
• Kilbridge, Kerry L.
• Choudhury, Atish D.
• Mortazavi, Amir
• Shah, Amishi Y.
• Venkatesan, Aradhana M.
• Bubley, Glenn J.
• Siefker‐Radtke, Arlene O.
• McKay, Rana R.
• Choueiri, Toni K.

Titel

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

Ist Teil von

• Cancer, 2021-03, Vol.127 (6), p.840-849

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. Patients with rare genitourinary malignancies have limited treatment options and are underrepresented in clinical trials. In this phase 2 trial, which has accrued 55 patients in less than 18 months, the combination of nivolumab and ipilimumab is active in a subset of patients with rare genitourinary malignancies, particularly those with bladder or upper tract carcinoma of variant histology (objective response rate 37%).