Nivolumab-ipilimumab combination confers durable responses in renal cell carcinoma
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A combination of nivolumab and ipilimumab conferred durable partial responses among certain patients with treatment-refractory advanced renal cell carcinoma, according to phase 2 study results presented at the virtual ASCO Annual Meeting.
“The safety profile of nivolumab [Opdivo, Bristol-Myers Squibb] and ipilimumab [Yervoy, Bristol-Myers Squibb] was similar to historical data in advanced renal cell carcinoma with this combination,” Toni K. Choueiri, MD, director of Lank Center for Genitourinary Oncology and the Kidney Cancer Center at Dana-Farber Cancer Institute, and Jerome and Nancy Kohlberg professor of medicine at Harvard Medical School, said during a presentation. “Although nivolumab and ipilimumab has been considered a standard-of-care option for advanced renal cell carcinoma since 2018 in the U.S. and since 2019 in Europe, the role of immunotherapy following progression on first-line checkpoint inhibitor therapy has not been well-established.”
In the open-label, randomized FRACTION-RCC study, researchers evaluated outcomes with nivolumab and ipilimumab after progression on checkpoint inhibitors among 46 patients (median age, 61 years; range, 36-82; 80% men; 94% white) with treatment-refractory advanced renal cell carcinoma.
One patient received no prior therapy; 10 had received one prior line; 12 had received two prior lines; 10 had received three prior lines; and 13 patients had received four or more prior lines.
All pretreated patients received prior anti-PD-L1 therapy, and 37 patients had undergone prior treatment with tyrosine kinase inhibitor-based therapy. Most patients (n = 44) had clear cell advanced renal cell carcinoma.
Patients received 3 mg/kg nivolumab plus 1 mg/kg ipilimumab every 3 weeks for four doses, followed after 6 weeks by 480 mg nivolumab monotherapy every 4 weeks for up to 2 years or until progression, toxicity or protocol-specified discontinuation.
Confirmed objective response rate using RECIST version 1.1, duration of response and PFS served as primary endpoints. Safety and tolerability served as secondary endpoints.
After a median follow-up of 8.9 months, researchers observed an ORR of 15.2%, with seven patients achieving partial response and no patients achieving complete response.
Duration of response ranged between 2 months and 19 or more months, and five patients experienced an ongoing response.
Six of the seven patients who responded to nivolumab plus ipilimumab had received two or more prior lines of therapy, researchers noted.
Thirty-six patients (78.3%) reported treatment-associated adverse events, including fatigue (19.6%), rash (19.6%), diarrhea (17.4%) and nausea (15%). Thirteen patients (28.3%) had grade 3 to grade 4 treatment-related adverse events, which included diarrhea (8.7%), increased amylase (6.5%) and increased lipase (6.5%).
Treatment-associated immune-mediated adverse events of any grade occurred among 47.8% of patients, including rash (19.6%) and diarrhea (17.4%). There were no treatment-related deaths.
“The safety profile of nivolumab and ipilimumab observed in this select group of patients was manageable,” Choueiri said. “The FRACTION-RCC trial offers a novel, efficient strategy for the assessment of therapies to provide new treatment options for [patients with advanced renal cell carcinoma] with high unmet needs.”
For more information:
Toni K. Choueiri, MD, can be reached at Dana-Farber Cancer Institute, 450 Brookline Ave., DANA 1230, Boston, MA 02215; email: toni_choueiri@dfci.harvard.edu.
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Choueiri TK, et al. Abstract 5007. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
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