Real-world outcomes of first-line therapies for unresectable hepatocellular carcinoma in the United States.

4079 Background: Unresectable hepatocellular carcinoma (uHCC) remains a significant clinical challenge despite advances in systemic therapies. Real-world evidence complements clinical trials by evaluating treatment effectiveness in diverse patient populations. This study assessed real-world progression-free survival (rwPFS) and overall survival (rwOS) for current standard-of-care first-line (1L) systemic therapies for uHCC. Methods: This retrospective study used the Flatiron Health database and included untreated uHCC patients diagnosed on or after January 1, 2018, who initiated 1L systemic therapies (atezolizumab + bevacizumab [atezo + bev], lenvatinib, sorafenib, or durvalumab + tremelimumab [durva + treme]) on or after May 29, 2020. Baseline characteristics, including ECOG status, ALBI grade, and demographic factors, were reported across cohorts. Kaplan-Meier method was used to estimate rwPFS and rwOS for each cohort. Results: A total of 1,539 patients were included: atezo + bev (n = 1,070), durva + treme (n = 238), lenvatinib (n = 139), and sorafenib (n = 92). Baseline characteristics were similar across cohorts. Most patients had ECOG (Eastern Cooperative Oncology Group) status 0–1 (57%–70%), with 15%–21% having ECOG 2+. ALBI (Albumin-Bilirubin) grade 2 was observed in 41%–60% of patients, while ALBI grade 3+ was present in 8.1%–17%. The median rwPFS for atezo + bev, lenvatinib, and durva + treme were similar at 4.7 months (95% CI: 4.1–5.4), 4.6 months (95% CI: 3.8–5.5), and 4.2 months (95% CI: 3.2–5.7), respectively. Sorafenib had a significantly shorter rwPFS at 3.0 months (95% CI: 2.5–4.4). The median rwOS for atezo + bev, lenvatinib, and sorafenib were similar at 10.7 months (95% CI: 9.5–11.8), 10.4 months (95% CI: 7.8–13.4), and 10.5 months (95% CI: 5.6–14.9). Durva + treme had a significantly shorter rwOS at 7.6 months (95% CI: 5.7–18.6). At 12 months, the survival probabilities for rwOS were 45% (95% CI: 42%, 48%) for Atezo + Bev, 41% (95% CI: 33%, 50%) for Durva+Treme, 45% (95% CI: 36%, 55%) for lenvatinib, and 43% (95% CI: 33%, 56%) for sorafenib. At 24 months, survival probabilities for rwOS were 27% (95% CI: 24%, 31%) for Atezo + Bev, 26% (95% CI: 19%, 36%) for lenvatinib, 21% (95% CI: 12%, 35%) for sorafenib, and data were undetermined for Durva + Treme. Conclusions: Findings from this real-world analysis show that atezo + bev demonstrated comparable outcomes versus lenvatinib, and potential benefits in rwPFS versus sorafenib and rwOS versus durva + treme. The median rwOS was approximately 10 months across treatments and highlights the need for novel therapies to improve long-term survival in uHCC. These results underscore the importance of evaluating treatment effectiveness in real-world populations, which may differ from clinical trial cohorts. Further analyses are warranted to explore these findings and optimize treatment strategies for uHCC.