Real-world efficacy of nivolumab plus cabozantinib in metastatic renal cell carcinoma (mRCC) using the IMDC.

Abstract

446 Background: Nivolumab plus Cabozantinib is an established first-line standard of care in mRCC after demonstrating significant improvements over Sunitinib in the phase III CheckMate 9ER trial. However, real-world outcomes with this regimen remain under-reported. Methods: Using the International mRCC Database Consortium (IMDC), we identified all patients treated with Nivolumab plus Cabozantinib between January 1, 2018, and August 31, 2025. Baseline characteristics were described, and median time to next treatment (mTTNT), overall survival (mOS), overall response rate (ORR), and subsequent treatment sequencing and efficacy were evaluated. OS was compared by IMDC risk group using log-rank. Results: 195 patients were identified. Baseline characteristics are summarized in Table 1. With a median follow-up of 18.9 months, the ORR was 41.6% (3.6% CR), mTTNT was 19.4m (95% CI 16.9-26.4) and mOS 44.4m (95% CI 29.6 m-NR). By IMDC risk group, mOS was NR (44.4–NR), 46.9m (26.4–NR), and 18.4m (11.5–NR) for favorable, intermediate, and poor risk, respectively (p<0.0001). At data cutoff, 91 patients were still on treatment, and 58 patients started a 2nd line. The most commonly used second line drugs were Axitinib (27.6%) and Lenvatinib plus Everolimus (17.2%). Others included Sunitinib (6.9%), Pazopanib (6.9%), Tivozanib (6.9%), Pembrolizumab plus Lenvatinib (5.2%) and Belzutifan (3.4%). Among patients treated with second-line Axitinib (n=16), ORR was 33.3%, with a mTTNT of 7.2m (95% CI 5.4–NR) and mOS of 12.3m (95% CI 5.4–NR). Conclusions: In this real-world analysis, Nivolumab plus Cabozantinib achieved TTNT and OS comparable to those reported in CheckMate 9ER, albeit with a somewhat lower ORR (41.6% vs 55.7%), likely influenced by the inclusion of non-clear cell histology. Importantly, 2nd line TKIs demonstrated activity following Cabozantinib exposure, supporting its use in this treatment sequence. Baseline characteristics. Characteristic N=195 (%) Median Age (IQR) 63 (56-71) Male 157 (80.5%) Non-clear cell 54 (27.7%) Nephrectomy 107 (54.9%) Brain metastasis 18 (9.3%) Bone metastasis 97 (49.7%) Liver metastasis 40 (20.5%) More than 1 metastasis site 141 (72.3%) IMDC risk (Fav/Int/Poor) 36 (21.7%) / 81 (48.8%) / 49 (29.5%)