442 Background: Cabo+Nivo and Len+Pem are very effective and approved 1L Rx for pts with mccRCC PMID:33657295, 33616314. However, after progression on these Rx, outcomes with 2L agents are not well established. Herein, we present Rx patterns and outcomes with 2L therapy after 1L Cabo+Nivo or Len+Pem in pts with mccRCC. Methods: This study used pt-level data from the US-based, electronic health record-derived deidentified Flatiron Health Research Database. Eligibility criteria: diagnosis of mccRCC, receipt of Cabo+Nivo (cohort 1) or Len+Pem (cohort 2) in 1L and documentation of 2L Rx. For both cohorts the data cut-off date was 10/31/2024. The primary endpoints were real-world time to next therapy (rwTTNT) and real-world overall survival (rwOS) from the start of 2L Rx and were summarized using median survival and 95% confidence interval (CI) via the Kaplan-Meier method. Results: Cohort 1 consisted of 238 pts treated with 1L Cabo+Nivo of which 66 who received 2L met eligibility and included in the analysis. These pts were diagnosed with mccRCC between 9/1/2012 – 10/5/2023, and initiated 2L from 8/23/2018 - 9/23/2024. Median age was 65 years (IQR 58, 76), 67% were White non-Hispanic and 71% were male. Cohort 2 consisted of 145 pts treated with 1L Len+Pem of which 37 received 2L and met eligibility and included in the analysis. These pts were diagnosed with mccRCC between 11/14/2014 – 2/2/2024 and initiated 2L from 6/29/2021 – 9/9/2024. Median age was 71 years (IQR 64, 76), 78% were White non-Hispanic and 68% were male. Rx patterns and survival outcomes summarized in Table. Conclusions: These data present Rx patterns after Cabo+Nivo or Len+Pem. 2L Rx in this setting retain modest activity. These findings underscore the limited efficacy of current 2L options in the post-Cabo+Nivo or Len+Pem setting, highlight the urgent need for novel therapies in this setting and provide survival estimates for future trial design and patient counseling. Rx patterns and survival outcomes of pts in cohort 1 and cohort 2. Rx in 2L Cohort 1 n(%) Cohort 1 median rwTTNT (mo) (95% CI) Cohort 1 median rwOS (mo) (95% CI) Cohort 2 n(%) Cohort 2 median rwTTNT (mo) (95% CI) Cohort 2 median rwOS (mo) (95% CI) TKI 21 (31.82%) 5.8 (3.0, —) 36 (5.0, —) 17 (45.95%) 4.6 (2.9, —) 14 (5.1, —) TKI + PD-1i 14 (21.21%) 12 (8.5, —) 19 (18, —) 10 (27.03%) 7.5 (5.2, —) 8.6 (5.2, —) CTLA-4i + PD-1i 12 (18.18%) 6.3 (2.6, —) 17 (9.1, —) 0 NA NA Single PD-1i 9 (13.64%) 18 (18, —) — (18, —) 3 (8.11%) — (2.1, —) — (—, —) HIF 2 (3.03%) 8.1 (7.4, —) — (—, —) 1 (2.70%) 3.1 (—, —) 3.1 (—, —) Other 8 (12.12%) 2.3 (1.4, —) — (3.5, —) 6 (16.22%) 4.9 (4.6, —) 6.5 (4.8, —) i = inhibitor.
murdock et al. (Sun,) studied this question.