Survival and adverse events of elderly patients treated with sorafenib for hepatocellular carcinoma

Elderly patients; Hepatocellular carcinoma; SorafenibPacientes ancianos; Carcinoma hepatocelular; SorafenibPacients grans; Carcinoma hepatocel·lular; SorafenibIntroduction: The first-line treatment for advanced hepatocellular carcinoma (HCC) is atezolizumab plus bevacizumab, but its availability is not universal and elderly patients are underrepresented in clinical trials. There is little evidence of efficacy and tolerability in elderly patients under systemic treatment. The aims of this study were to characterize the profile of elderly patients treated with sorafenib, assess their survival and safety profile in order to extrapolate their eligibility for systemic treatment. Methods: Retrospective multicentre study of HCC patients aged ≥75 years old treated with sorafenib from January 2008 to December 2019. Demographic data, baseline characteristics, and variables related to HCC and sorafenib were recorded. Overall survival (OS) and safety were analyzed. Results: The study included 206 patients from 11 hospitals, median age 77.9 years; 71.4% men and 62.6% stage Barcelona Clinic Liver Cancer- C (BCLC-C). The main causes of cirrhosis were hepatitis C (60.7%) and alcohol (14.7%). Most patients (84.5%) started with sorafenib 800mg and 15.5% at lower dosage. Arterial hypertension (AHT) (74.2 vs 62.2%; standardized mean differences (STD): 26) and baseline ECOG-PS>0 (45.3 vs 34.7%; STD: 38.2) differed significantly between patients receiving low and full doses. Median OS was 15.4 months (18.2 in BCLC-B vs 13.6 in BCLC-C). OS was not modified by comorbidities, age or period with more expertise. Conclusions: Sorafenib appears to be safe in elderly patients with HCC. This is the first study to characterize the profile of elderly patients to be considered for systemic treatment. These findings could be used as the reference profile for elderly candidates for atezolizumab-bevacizumab.AS: Travel grants from Tillots, Ferring, Norgine, Alfasigma, Jansen, Abbvie. MC: None. ZV: None. SM-M: None. VS: Travel grants from Bayer. Consultancy LEO Pharma. MP: None. LC: None. RG: None. AG: None. BM: Consultancy: Bayer-Shering Pharma, Eisai-Merck. Conferences/lectures: Eisai, MSD, Roche. Research grant: Lab Viñas. Funding: BM is funded by grants PI18/00961 and PI21/00714 from Instituto de Salud Carlos III. DH. None. AC. None. SM. Conferences/lectures: Bayer. Travel grants: Bayer, and Eisai. MRo. None. MRe. Consultancy: Bayer-Shering Pharma, BMS, Roche, Ipsen, AstraZeneca, Lilly. BTG/Paid conferences: Bayer-Shering Pharma, BMS, Gilead, Lilly. Research Grants: Bayer-Shering Pharma, Ipsen. MV. Travel grants: Gilead, MSD, Bayer, Abvie. Conferences/lectures: MSD, Gilead, Abvie, Eisai

Non-Invasive Tests of Liver Fibrosis Help in Predicting the Development of Hepatocellular Carcinoma among Patients with NAFLD

Carcinoma hepatocelular; Elastografía transitoriaCarcinoma hepatocel·lular; Elastografia transitòriaHepatocellular carcinoma; Transient elastographyBackground: The potential role of non-invasive tests (NITs) for liver fibrosis for hepatocellular carcinoma (HCC) prediction remains poorly known. Methods: Retrospective analysis of a NAFLD cohort from a single university hospital in Barcelona, Spain. Incidence rates and cumulative incidence for the overall cohort, as well as cirrhotic and non-cirrhotic patients were calculated. Logistic regression analyses were carried out to investigate risk factors of HCC. Results: From the entire cohort of 1040 patients, 996 patients (95.8%) were analyzed, in whom 35 cases of HCC were detected, of which 26 (72.4%) HCC incident cases were newly diagnosed during a median follow-up of 2.5 (1.9–3.6) years. Two-hundred and thirty-one (23.2%) were cirrhotic at baseline. With the exception of 2 (7.7%) cases of HCC, the rest were diagnosed in cirrhotic patients. Overall HCC cumulative incidence was 9.49 (95% CI 6.4–13.9) per 1000 person-years. The incidence rate for cirrhotic patients was 41.2 (95% CI 27.6–61.6) per 1000 person-years and 0.93 (95% CI 0.23–3.7) per 1000 person-years for patients without cirrhosis. Overall mortality was significantly higher amongst patients with HCC (4.4% vs. 30.8%, p < 0.001). In patients with available liver biopsy (n = 249, 25%), advanced fibrosis (F3–F4) was significantly associated with higher HCC incidence, but not steatosis, lobular inflammation, nor ballooning. In the overall cohort, FIB-4 ≥1.3 (HR 8.46, 95% CI 1.06–67.4, p = 0.044) and older age (HR 1.06, 95% CI 1.01–1.11, p = 0.025) were associated with increasing risk of HCC over time, whereas in cirrhotic patients predictors of HCC included decreasing values of albumin (HR 0.34, 95% CI 0.13–0.87, p = 0.024), platelets (HR 0.98, 95% CI 0.98–0.99, p = 0.001), and increasing values of liver stiffness (HR 1.03, 95% CI 1.00–1.06, p = 0.016). Conclusions: In a Spanish cohort of NAFLD patients, HCC was rare in non-cirrhotic patients. NITs might play a relevant role at predicting HCC.The study was conducted in accordance with the Declaration of Helsinki and approved by the Vall d’Hebron University Hospital Campus Institutional Review Board (study protocol code PR(AG)626/2021)