Real-world efficacy and survival outcomes of novel targeted therapies in advanced hepatocellular carcinoma from low- and middle-income countries.

99 Background: Advanced hepatocellular carcinoma (aHCC) has a dismal prognosis, with a median survival of 8-10 months. Immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) are now the standard of care for patients with aHCC. Limited information is available on access to and efficacy of new targeted treatments, response patterns, and survival among patients from lower-middle-income countries (LMICs) in the era of new therapies. Methods: This retrospective study included 666 patients with advanced HCC treated at two tertiary care hospitals. Baselines included age, gender, etiology of liver disease, socioeconomic status, ECOG performance status, Child-Pugh score, BCLC stage, and cirrhosis. Systemic treatments included tyrosine kinase inhibitors and immunotherapy-based regimens. Patients who had received prior or additional locoregional therapies. Multivariable logistic regression analysis was performed to identify predictors of treatment response. Overall survival (OS) was estimated using Kaplan-Meier curves. Results: A total of 666 patients with advanced hepatocellular carcinoma were included. The mean age at diagnosis was 60.23 ± 9.38 years. Male patients accounted for 484 (72.7%), whereas female patients accounted for 182 (27.3%) of the cohort. The most common underlying etiology of liver disease was HCV (81.6%). At presentation, 532 patients (75%) had Child-Pugh A. TKI was administered to 545 patients (81.8%), including sorafenib in 298 patients (45.1%) and lenvatinib in 247 patients (38.7%). Immunotherapy was received by 121 patients (18.2%). Locoregional therapies were used in 146 patients (21.9%) either prior to or alongside systemic therapy. On multivariable logistic regression analysis, ECOG performance status and hepatic function were independently associated with better survival in patients. Median OS was 12 months. With immunotherapy, OS improved to 18 months, compared with 12 and 10 months with Lenvatinib and Sorafenib, respectively. Conclusions: ICIs significantly improved the OS in HCC. The costs of IO therapies need to be significantly reduced to make this therapy a viable option for the vast majority of our patients in LMICs. We are planning prospective clinical trials to evaluate the efficacy and feasibility of low-dose immunotherapy, with the rationale of expanding access to immunotherapy for patients who are unable to afford standard-dose treatment.