Lenvatinib for unresectable hepatocellular carcinoma: the first Indian experience

The AsiaPacific region contributes to nearly 73% of global deaths due to hepatocellular carcinoma (HCC).1 The ageadjusted annual HCC incidence rate (per 100,000 persons) in India ranges between 0.7 and 7.5 for men and 0.2 and 2.2 for women.2 Most patients present in the advanced stage when definitive therapies are not possible.3 Lenvatinib was a breakthrough in the treatment of unresectable HCC (uHCC).4 However, there is no Indian data on lenvatinib therapy. In this report, we describe the outcomes of uHCC patients treated with lenvatinib. We retrospectively analysed the data of patients who were treated with lenvatinib as firstline systemic therapy at our tertiary care centre from January 2019 to February 2021. The data were analysed using SPSS software 25 version. Descriptive statistics have been expressed as mean (±SD) for continuous data. For categorical data, we have expressed the results as a percentage (n). KaplanMeier analysis was used to assess the median overall survival (OS) and progressionfree survival (PFS). A total of 63 patients received lenvatinib. The mean age was 60.24 ± 9.57 years. Males were predominant (93.7%). Viral hepatitis (50%) was the most common cause of liver disease, followed by nonalcoholic steatohepatitis (44.5%) and alcohol (6.3%). Twentytwo percent (14/63) of patients were noncirrhotic HCC. The mean αfetoprotein (AFP) before initiation of lenvatinib was 1120.71 ± 2369.55 ng/mL. All the patients had ≤1 Eastern Cooperative Oncology Group performance status. Thirtyfive percent of patients had received a prior radiological intervention (Table 1). Sixtytwo percent (39/63) of patients were initiated on 8 mg dose and the rest on 12 mg dose based on the weight. Fiftysix percent (35/63) of patients developed adverse events. The median tolerated dose was 8 mg/d in the whole cohort. The median duration of therapy was 4.1 months. Adverse events noted were hypertension (13/63, 21%), nausea (6/63, 10%), diarrheoa (5/63, 8%), palmarplantar erythrodysesthesia syndrome (4/63, 6.35%), fatigue (3/63, 5%), skin rash (2/63, 3.17%) and abdominal pain (1/63, 1.6%). One patient developed tumour rupture (size 10.3 × 7.1 cm) after 27 days of therapy. Treatment was discontinued in 20% (12/63) of patients due to adverse events. Seven patients were started on regorafenib, given the progressive disease. On KM analysis, the median PFS was 5 (95% CI, 4.275.72) months, and the median OS was 10.4 (95% CI, 8.2412.56) months. Fiftytwo patients were evaluated by modified Response Evaluation Criteria in Solid Tumors (mRECIST). While none of the patients achieved complete response, 27% (14/52) achieved partial response, 44.2% (23/52) had stable disease, and the disease progressed in 29% (15/52) of patients. Lenvatinib is a multikinase inhibitor which is now one of the firstline therapy recommended for uHCC. The first study by Kudo et al demonstrated noninferiority of lenvatinib compared to sorafenib.4 The median PFS was significantly better with lenvatinib than sorafenib.4 Recently, Goh et al evaluated 111 patients treated with lenvatinib for uHCC. OS was 10.5 months, and PFS was 6.2 months in the realworld experience. The results of our study are similar to the experience of Koh et al5 The major limitation of our study is the retrospective evaluation of the data and lack of comparison with patients who received sorafenib. However, this is the first Indian data on the safety and efficacy of Lenvatinib for uHCC.