A real-world comparison of nivolumab plus cabozantinib and pembrolizumab plus lenvatinib focusing on safety outcomes in metastatic renal cell carcinoma: results from the JK-FOOT consortium.
Immune checkpoint inhibitor (ICI)-based combination therapy is a standard first-line treatment for metastatic renal cell carcinoma (mRCC), with combinations such as nivolumab plus cabozantinib (Nivo + Cabo) and pembrolizumab plus lenvatinib (Pem + Len) demonstrating favorable oncologic outcomes. However, no direct comparisons between these two regimens have been conducted. This study aimed to compare the safety and oncologic outcomes of Nivo + Cabo and Pem + Len in patients with mRCC.
This retrospective study included 185 patients with mRCC treated with Nivo + Cabo (n = 81) or Pem + Len (n = 104) between January 2018 and June 2025 across multiple institutions. The primary outcome was a comparison of treatment-related adverse events (TrAEs). Oncologic outcomes, including objective response rate (ORR), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS), were compared using one-to-one propensity score matching.
Any-grade TrAEs occurred in 90% of patients in the Nivo + Cabo group and 92% in the Pem + Len group (p = 0.6). Severe TrAEs (grade ≥ 3) were more frequent in the Pem + Len group (44%) than in the Nivo + Cabo group (30%, p = 0.048). Tyrosine kinase inhibitor dose reduction and treatment discontinuation rates were similar between groups. In the matched cohort (Nivo + Cabo: n = 74; Pem + Len: n = 74), ORRs were comparable (66% vs. 71%, p = 0.6). With a median follow-up of 17 months, no significant differences were observed in PFS (p = 0.4), CSS (p = 0.9), or OS (p = 0.5).
Nivo + Cabo and Pem + Len demonstrated similar oncologic efficacy as first-line treatments for mRCC. However, Pem + Len was associated with more severe TrAEs. Careful toxicity management and shared decision-making are essential when selecting ICI-based combinations.
This retrospective study included 185 patients with mRCC treated with Nivo + Cabo (n = 81) or Pem + Len (n = 104) between January 2018 and June 2025 across multiple institutions. The primary outcome was a comparison of treatment-related adverse events (TrAEs). Oncologic outcomes, including objective response rate (ORR), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS), were compared using one-to-one propensity score matching.
Any-grade TrAEs occurred in 90% of patients in the Nivo + Cabo group and 92% in the Pem + Len group (p = 0.6). Severe TrAEs (grade ≥ 3) were more frequent in the Pem + Len group (44%) than in the Nivo + Cabo group (30%, p = 0.048). Tyrosine kinase inhibitor dose reduction and treatment discontinuation rates were similar between groups. In the matched cohort (Nivo + Cabo: n = 74; Pem + Len: n = 74), ORRs were comparable (66% vs. 71%, p = 0.6). With a median follow-up of 17 months, no significant differences were observed in PFS (p = 0.4), CSS (p = 0.9), or OS (p = 0.5).
Nivo + Cabo and Pem + Len demonstrated similar oncologic efficacy as first-line treatments for mRCC. However, Pem + Len was associated with more severe TrAEs. Careful toxicity management and shared decision-making are essential when selecting ICI-based combinations.
Authors
Yanagisawa Yanagisawa, Mori Mori, Kawada Kawada, Katayama Katayama, Tsujino Tsujino, Maenosono Maenosono, Toyoda Toyoda, Nukaya Nukaya, Morinaka Morinaka, Tamura Tamura, Fukuokaya Fukuokaya, Urabe Urabe, Murakami Murakami, Bekku Bekku, Takahara Takahara, Fujita Fujita, Azuma Azuma, Araki Araki, Inamoto Inamoto, Komura Komura, Kimura Kimura,
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