Site-specific disease progression in patients with metastatic renal cell carcinoma treated with first-line nivolumab plus ipilimumab or axitinib-based immunotargeted combinations.

478 Background: Data on site-specific progression patterns in metastatic renal cell carcinoma (mRCC) treated with immuno-oncology agents are limited. This study aimed to characterize sites of progression in patients receiving nivolumab plus ipilimumab (Nivo-Ipi) or axitinib-based immunotargeted combinations in the first-line setting. Methods: A retrospective, observational cohort study included patients with clear-cell mRCC who received either Nivo-Ipi (Cohort A) or pembrolizumab-axitinib and avelumab-axitinib (Cohort B) from 2018 to 2024. The primary objective was to assess the occurrence of new lesions in different organs. Secondary analysis evaluated disease progression by an increase of more than 20% in target lesion size. Results: A total of 334 patients were identified, with radiographic progression observed in 86.3% (107/124) of Cohort A and 60% (126/210) of Cohort B. In the ITT population (n=233), the median age at mRCC diagnosis was 59.7 years (range 31–84), 79% were male, 74% had undergone nephrectomy, 61% had intermediate IMDC risk, and 64% had two or more metastatic sites. Cohort B had a younger median age (60.2 vs. 65.4 years), a higher incidence of bone metastases (28.6% vs. 13.1%), and more favorable risk (15.1% vs. 0.9%) compared to Cohort A. The site-specific rate of new lesions differed between cohorts (Table). Progression due to increased target lesions occurred in 60.7% (65/107) of Cohort A and 77.8% (98/126) of Cohort B patients. Conclusions: New lesion development was more frequent with Nivo-Ipi, with lymph nodes being the most common site of new lesions of mRCC across both cohorts. Cohort An=107 Cohort Bn=126 Baseline At the time of progression Baseline At the time of progression Patients with new lesions, n (%) - 42 (39.3) - 28 (22.2) Sites of metastases, n (%) Lung 73 (68) 81 (76) 76 (60) 79 (63) Lymph node 55 (51) 94 (88) 68 (54) 81 (64) Liver 27 (25) 28 (26) 39 (31) 47 (37) Bone 14 (13) 26 (24) 36 (29) 41 (33) Adrenal gland 19 (18) 20 (19) 20 (16) 28 (22) Contralateral kidney 5 (5) 5 (5) 1 (0.8) 2 (1.6) Brain 1 (1) 2 (2) 4 (3) 4 (3) Soft tissues 4 (4) 4 (4) 1 (0.8) 1 (0.8) Pancreas 2 (2) 3 (3) 0 (0) 2 (1.6) Other* 5 (5) 7 (7) 9 (7) 9 (7) *Thyroid gland, pleura, peritoneum, ovary, breast.