Effectiveness of Generic Lenvatinib in Advanced Hepatocellular Carcinoma in Low and Middle-Income Countries

Objective: This study aims to assess the near equivalence of generic Lenvatinib to the patented Lenvatinib in patients with advanced hepatocellular carcinoma (HCC) in low-and middle-income countries (LMICs), with the goal of enhancing patient access and reducing financial burden, ultimately improving treatment adherence. Materials and Methods:This is a multi-centric retrospective cohort analysis of 2 cancer centres in Pakistan.Patients who received Lenvatinib between January 2023 and July 2024 for managing advanced HCC were enrolled.Inclusion criteria were radiologically confirmed advanced Hepatocellular Carcinoma, age > 18 years, ECOG status of 0-2, complete medical records.Patients were excluded if they had ECOG status of 3-4, Brain metastasis, pregnant/lactating females, or incomplete records.The primary endpoint was progression-free survival (PFS).The following factors were reviewed: ECOG, performance status, comorbidities, risk factors, etiology of cirrhosis, Child-Pugh score, prior treatment, and socioeconomic status.Tumour assessment was determined by reviewing radiology reports.Progression-free survival was determined by the Kaplan-Meier method.Confidence intervals were calculated where applicable, using SPSS version 26. Results:The study included 56 patients with a median age of 60 years.Chronic hepatitis C virus infection C (89.2%) was the predominant cause of liver disease, followed by chronic hepatitis B virus infection.75% patients belonged to Child-Pugh class A at baseline.At baseline, tumor size > 5cm was present in 73.2% of patients, 14.3% had multifocal lesions, 44.6% had angioinvasion, and 23.2% had distant metastasis.53.6% had received prior therapies, including trans-arterial chemoembolization (TACE) and or Sorafenib.46.4% had not received any previous treatment.83.9% received follow-up imaging at 4 months.The median number of cycles given was 5 and mPFS was 11.73 months (comparison is indirect and based on historical data such as the REFLECT trial).The response evaluation according to mRECIST criteria showed that 5.4% of patients achieved a complete response (CR), 19.6% had a partial response (PR), 23.2% experienced stable disease (SD), and 35.7% had progressive disease (PD).Additionally, 16.1% of patients did not complete their re-evaluation, with 14.3% primarily due to premature discontinuation of the drug due to toxicities such as diarrhea, hand foot syndrome (5.4%) and decompensation of liver disease (3.6%).Currently, 89.3% of patients are alive, 5.4% died, and the same ratio lost to follow-up Conclusions:The study demonstrated that generic Lenvatinib is an effective treatment option for advanced HCC in low-and middleincome countries (LMICs) patients, with a median progression-free survival (PFS) of 11.73 months (95% CI = 9.7,13.6),compared to 12.5 months.