Résumé
BackgroundAdvanced hepatocellular carcinoma (HCC) is a global health challenge, and while immunotherapy-based combination are now standards of care as first-line treatment, there is a paucity of data regarding second-line treatment following immunotherapy. We aimed to study the access to second-line treatment, comparing patients initially treated with Sorafenib (Sor) to those with atezolizumab-bevacizumab (AB).MethodsThis study included patients from the real-world prospective CHIEF cohort and aimed to get insight into Systemic treatment sequences in patients with advanced HCC (STRETCH). Median overall survival (mOS) and median progression free survival (mPFS) were defined since the beginning of the 2d line setting.ResultsBetween September 2019 and September 2024, 1103 patients received either AB (n=899) or Sor (n=204) as first-line treatment. Most patients were Child-Pugh A (77.1% AB vs. 70.3% Sor; p=0.06); BCLC-C (66.3% AB vs. 84.3% Sor; p<0.001) and ALBI grade 2 (61.2% AB vs. 64.9% Sor; p=0.021). mOS and mPFS were 22.3 [18.5–27.4] and 5.6 [5.2–6.4] months for AB, compared to 9.4 [7.3–12.7] months (p<0.0001) and 3.5 [3.1–4.0] months (p=0.11) for Sor. Among 456 patients progressing on AB, 42.1% received second-line treatment versus 60.0% of 130 patients progressing on Sor (p<0.0003). In second-line, after AB, patients receiving tyrosine kinase inhibitors (TKI) had an mOS of 13.0 [9.8–15.5] months (n=136, 70.8%), while those on immunotherapy (n=24) or combinations (n=24) had non-reached mOS (p=0.00088). The mOS for second-line TKI was similar regardless of first-line treatment (8.6 months after Sor; p=0.082). No significant differences were found between Sor (n=78), lenvatinib (n=35), regorafenib, or cabozantinib (n=23) (p=0.83), though lenvatinib showed a trend for improved mPFS.ConclusionsThis unique prospective cohort provides real-world data on second-line treatment practices. Access to second-line treatment was lower after AB than Sor, but survivals under second-line TKI were similar. While second-line immunotherapy following immunotherapy shows promising results, these are likely influenced by patient selection for rechallenge.