First-line IO Combination Therapies in mRCC

Ipilimumab plus nivolumab is a first-line combination treatment option in patients with metastatic renal cell carcinoma (mRCC). Data from recent studies have demonstrated the efficacy of first-line immune-oncology vascular endothelial growth factor (IO-VEGF) inhibitor combinations. There are limited data on comparative data between those two strategies; the efficacy of subsequent therapies is also unknown.

Shaan Dudani, MBChB, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada, and colleagues conducted a comparative analysis of the two treatment strategies. They reported results of the analysis during a poster session at the ASCO 2019 Annual Meeting in a poster titled First-line (1L) Immuno-oncology (IO) Combination Therapies in Metastatic Renal Cell Carcinoma (mRCC): Results from the International mRCC Database Consortium (IMDC).

The researchers utilized the International Metastatic RCC Consortium (IMDC) data base to compare patients treated with any first-line IO-VEGF combination with those treated with ipilimumab plus nivolumab. To control for imbalances in IMDC risk factors, the researchers used multivariable Cox regression models.

A total of 188 patients received first-line IO combination therapy; of those 113 were treated with IO-VEGF combinations and 75 with ipilimumab plus nivolumab. The two groups were similar in baseline characteristics and IMDC risk factors.

Comparing IO-VEGF combinations versus ipilimumab plus nivolumab, first-line response rate (RR) was 33% versus 40%, time to treatment failure (TTF) was 14.3 months (95% confidence interval [CI], 9.2-16.1) versus 10.2 months (95% CI, 6.7-15.1), and median overall survival was not reached [NR] (95% CI, 22.3-NR) versus not reached (95% CI, 35.1-NR). Following adjustment for IMDC risk factors, the hazard ratio for time to treatment failure was 0.71 (95% CI, 0.46-1.12) and the hazard ratio for death was 1.74 (95% CI, 0.82-3.68).

There was variation in second-line treatments. Among patients who received subsequent VEGF-based therapy, second-line response rate was lower in the IO-VEFG cohort (n=20) than in the ipilimumab plus nivolumab cohort (n=20): 15% vs 45%; P=.04). There was no significant difference in time to treatment failure between the two cohorts. The use of immune-oncology following IP-VEGF treatment was uncommon; three of five patients had progressive disease as best response; two of five had partial response/stable disease but their first-line IO-VEGF exposure was short (<3 months).

“There does not appear to be a superior first-line immune-oncology combination strategy in mRCC, as IO-VEGF combinations and ipilimumab plus nivolumab have comparable first-line response rate, time to treatment failure, and overall survival. Most patients received VEGF-based therapy in the second line. In this group, second-line response rage was greater in patients who received ipilimumab plus nivolumab, though there was no difference in second-line time to treatment failure,” the researchers said.

Source: Dudani S, Graham J, Wells C, et al. First-line (1L) immune-oncology (IO) combination therapies in metastatic renal cell carcinoma (mRCC): Results from the international mRCC database consortium (IMDC). Abstract of a poster presented at the American Society of Clinical Oncology 2019 Annual Meeting, June 3, 2019, Chicago, Illinois.