Dados do Trabalho

Título

REAL-WORLD CONTEXT OF HEPATOCELLULAR CARCINOMA PATIENTS AFTER SORAFENIB TREATMENT: ELIGIBILITY TO SECOND-LINES AND PROGNOSTIC FACTORS

Introdução

In the past years, novel drugs were adopted in hepatocellular carcinoma (HCC) after sorafenib failure. Placebo-controlled trials demonstrated improved overall survival (OS) with regorafenib (RESORCE trial), cabozantinib (CELESTIAL), and ramucirumab (REACH-2). In addition, immune checkpoint inhibitors (ICI) were approved based on durable response rates in phase II studies. However, strict eligibility criteria in clinical trials limit the adoption of these drugs in the practice.

Objetivo

In this study, we aimed to characterize a real-world cohort of HCC patients after progression to sorafenib and apply trial eligibility criteria for subsequent therapies.

Método

HCC patients treated with sorafenib between Jan/2017 and Nov/2019 were included. We retrospectively assessed clinical and laboratorial data at the time of progression to sorafenib and evaluated the eligibility to CELESTIAL, RESORCE, REACH-2 and to phase II immunotherapy trials. Median OS (mOS) after sorafenib progression was estimated by Kaplan Meier methods and prognostic factors were determined using a Cox regression model.

Resultado

125 patients were included: 69.2% male, 92.8% Child-Pugh A, 62.3% HCV etiology, 81.6% BCLC stage C and 50.4% received previous locoregional therapies. Median sorafenib duration was 6.5 months (IQR: 4.7-8.4), median OS was 8.2 (CI95% 6.5-10.1) and the median post sorafenib-progression survival (mPPS) was 2.9 months (CI95% 1.9-4.1). According to trial eligibility, 28.8% would be eligible for cabozantinib, 24% for regorafenib, 11.2% for ramucirumab and 29.6% for ICI. Of those eligible for any second-line trial (n=49, 39.2%) mPPS was 8.0 months (CI95% 3.1-18.9) vs 1.7 months (CI95% 0.4-3.6) for those ineligible (p<0.001). Prognostic factors independently associated with PPS were: ECOG PS 0-1 vs 2-4 (p<0.001), Child-Pugh A-B7 vs >B7 (p<0.001), AFP<200 ng/ml (0.04) and absence of new extrahepatic lesion vs progression with new metastasis (p<0.001).

Conclusão

A small proportion of HCC patients would be eligible for second-line therapies according to trial eligibility. Liver function, AFP, and the pattern of progression can help to stratify patients into prognostic subgroups. Real-world data will be important to determine if subgroups not included in clinical trials may benefit from novel agents.

Palavras-chave

hepatocellular carcinoma, sorafenib, second-line therapy