Frontline Axitinib Plus Pembrolizumab vs Ipilimumab Plus Nivolumab for Metastatic Renal Cell Carcinoma

For patients with metastatic clear cell renal cell carcinoma treated with either combination axitinib plus pembrolizumab or combination ipilimumab plus nivolumab, there was no difference in median or 24-month survival between the 2 treatment groups. However, when patients were stratified by International Metastatic RCC Database Consortium (IMDC) risk criteria, axitinib-pembrolizumab conferred a benefit to real-world progression-free survival (PFS) and overall survival (OS) within the favorable risk population.

Kevin Zarrabi, MD, Sidney Kimmel Cancer Center-Thomas Jefferson University, Philadelphia, PA, and colleagues pointed out “There are no prospective clinical trials comparing recommended front-line therapy options in [metastatic renal cell carcinoma]. Both the KEYNOTE-426 and CheckMate-214 studies compared their respective combination therapy [axitinib-pembrolizumab and ipilimumab-nivolumab, respectively] to sunitnib, which is no longer a category 1 National Comprehensive Cancer Network recommended treatment.” The authors went on to say, “In the absence of prospective studies, retrospective analyses may provide guidance for clinicians in choosing front-line treatments.”

This retrospective, real-world study, included 1506 patients with metastatic clear cell renal cell carcinoma from the Flatiron Health database treated with either frontline axitinib plus pembrolizumab (n = 547) or frontline ipilimumab plus nivolumab (n = 959) between 2018 and 2022. Using underlying risk criteria, the IMDC score was determined for all patients: 6.4% with favorable risk, 82.3% with intermediate/poor risk, and 11.4% with an unknown risk. The primary outcomes of this study were OS and real-world progression-free survival (PFS), defined as time in months from the date of initiation of frontline treatment to death or disease progression.

The median follow-up duration was 20 months (range, 0.2 to 47.6). The real-world PFS for patients treated with axitinib-pembrolizumab was 10.6 months and 6.9 months for those treated with ipilimumab-nivolumab (P = .04). When stratified by IMDC risk criteria, the median real-world PFS for patients with a favorable risk was 25.5 months for those treated with axitinib-pembrolizumab and 6.9 months for those treated with ipilimumab-nivolumab (P = .01). In the intermediate/poor risk strata, the median real-world PFS was 9.5 months for axitinib-pembrolizumab and 6.4 months for ipilimumab-nivolumab. The adjusted median OS for patients treated with axitinib-pembrolizumab was 28.9 months, compared to 24.3 for those treated with ipilimumab-nivolumab (P = .09). Study authors also noted that an IMDC risk score of intermediate/poor was associated with a significantly increased likelihood of being treated with ipilimumab-nivolumab therapy (odds ratio, 2.09; 95% confidence interval, 1.27 to 3.45; P = .004)

Dr Zarrabi et al concluded, “Our study reveals no discernible difference in survival…between patients treated with [ipilimumab-nivolumab] or [axitinib-pembrolizumab].” They went on, “The decision of treatment remains patient centered, accounting for known toxicities, patient co-morbidities, and patient goals of care.”

Source:

Zarrabi KK, Handorf E, Miron Benjamin, et al. Comparative effectiveness of front-line ipilimumab and nivolumab or axitinib and pembrolizumab in metastatic clear cell renal cell carcinoma. Oncologist. Published online October 6, 2022. doi:10.1093/oncolo/oyac195