ArticleInternational journal of clinical oncology2026
Clinical efficacy and safety of second-line cabozantinib after first-line immune checkpoint inhibitor-based combinations in metastatic renal cell carcinoma: a multicenter retrospective study.
Article in International journal of clinical oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThe efficacy of second-line cabozantinib following first-line immune checkpoint inhibitor (ICI)-based combinations, particularly after pembrolizumab plus lenvatinib (Pem + Len), remains uncharacterized. We evaluated real-world outcomes in patients with metastatic renal cell carcinoma (mRCC).
methodsThis multicenter retrospective study included 96 mRCC patients who initiated second-line cabozantinib between 2021 and 2025, after first-line ipilimumab plus nivolumab (Ipi + Nivo; n = 36), avelumab or pembrolizumab plus axitinib (Ave/Pem + Axi; n = 30), or Pem + Len (n = 30). Endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) from cabozantinib initiation and from first-line therapy initiation, prognostic factors, and safety.
resultsThe overall ORR was 36% (Ipi + Nivo: 40%; Ave/Pem + Axi: 43%; Pem + Len: 23%). The median PFS from cabozantinib initiation was 9.4 months (Ipi + Nivo: 9.4; Ave/Pem + Axi: 15.9; Pem + Len: 8.7; P = 0.57), and the median OS was 25.5 months (P = 0.87). From first-line therapy initiation, the median PFS (27.1 months) and OS (42.2 months) did not differ significantly across groups (P = 0.70; P = 0.91). On multivariate analysis, only IMDC poor risk was independently associated with PFS. Grade ≥ 3 treatment-related adverse events occurred in 34.4% of patients.
conclusionSecond-line cabozantinib provided meaningful efficacy across all approved first-line ICI-based combinations. Cumulative PFS from first-line therapy initiation was similar across regimens, although OS data for the Pem + Len group remain immature. Cabozantinib appears to represent a reasonable second-line option in the ICI era.
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