A single arm phase II trial of capecitabine and erlotinib in patients with advanced hepatocellular carcinoma after first-line failure (CAPER- HCC study)

Low dose capecitabine in combination with erlotinib has potential anti-tumor activity with limited toxicity, a cost-effective option for advanced hepatocellular carcinoma (HCC). Current second-line systemic therapies are of limited reach for lower-middle-income countries (LMIC).

Patients more than 17 years old having ECOG PS 0-2, with advanced (BCLC B or C) HCC failing (progressed or intolerant to) first-line therapy, were enrolled in phase 2 single-arm study. Erlotinib 100mg once a day and capecitabine 500mg twice a day till progressive disease or intolerable side effects were administered. The primary endpoint was to achieve 30 % Progression-free survival (PFS) at 6 months with the capecitabine with erlotinib combination compared to 10% at 6 months in the historical cohort. Secondary objectives include Overall survival (OS), safety, and Response rate (RR).

Fifteen patients received at least one month of study medications. The median age was 62 years with 14 (93.3%) males. Hepatitis B was the most common cause of HCC in 6 (40%). The median Child-Pugh score was 5 (range; 5-7) and BCLC stage was C for all patients at the time of enrolment. One patient (16.67%) achieved disease stabilization. For all 15 patients enrolled, the median PFS was 2.0 (95% CI 1.25- 2.74) months and OS was 3.0 (95% CI 1.95- 4.0) months with a progression-free survival rate of less than 10% at 6 months. Due to poor efficacy in futility analysis, the study has stopped further enrollment. The regimen was well tolerated with grade 3 diarrhea and grade 3 erlotinib induced rash in 1 patient each, while grade 3 fatigue was seen in 2 (13.3%) patients with consequent dose modification/ interruptions requirement in 3 (20%) patients.

Low dose capecitabine in combination with erlotinib was well tolerated but did not reach the preplanned efficacy criteria of progression-free survival. Future studies evaluating this combination in advanced HCC may consider using different dosing strategies.

CTRI/2021/01/030657 (Clinical Trial Registry of India).

The authors.

Shila medicare private limited provided grants to the institute to support this study. They had no say in the design or the results of the study.

P. Bhargava: Honoraria (Institution): Pfizer Ltd, Novartis Ltd, Intas Ltd; Advisory / Consultancy: Glenmark pharmaceutical Ltd; Research grant / Funding (institution): Dr. Reddy laboratory Pvt Ltd., Cadila health care pvt Ltd., Shilpa Medicare Pvt Ltd. V. Ostwal: Advisory / Consultancy: AstraZeneca ; Research grant / Funding (institution): Dr. Reddy's Lab Pvt limited, Zydus Cadilla Pvt Ltd; Travel / Accommodation / Expenses: AstraZeneca. All other authors have declared no conflicts of interest.