Adding lenvatinib plus pembrolizumab to TACE improves PFS in intermediate-stage HCC

Treatment with lenvatinib plus pembrolizumab in combination with transarterial chemoembolisation (TACE) was superior to TACE alone in patients with intermediate-stage hepatocellular cancer (HCC) who are not amenable to curative treatment, as demonstrated by the first results of the LEAP-012 study.

For decades, the standard treatment of intermediate-stage HCC has been TACE; however, survival has been modest (median overall survival [OS] 26–30 months) [1,2]. Lenvatinib is a first-line treatment option for patients with unresectable HCC who are ineligible for or refractory to TACE [3]. In the previous LEAP-002 study, first-line lenvatinib plus pembrolizumab showed a trend for prolonged OS compared with lenvatinib alone in patients with advanced HCC [4].

The ongoing, randomised, phase 3 LEAP-012 trial (NCT04246177) aimed to evaluate the efficacy and safety of lenvatinib plus pembrolizumab in combination with TACE versus TACE alone in patients with intermediate-stage HCC. LEAP-012 enrolled 480 participants with confirmed HCC not amenable to curative treatment and with ≥1 measurable lesion. They were 1:1 randomised to receive lenvatinib plus pembrolizumab plus TACE or dual placebo plus TACE. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Prof. Josep Llovet (Icahn School of Medicine at Mount Sinai, NY, USA) presented the results of the first interim analysis [5].

After a median follow-up of 25.6 months, the median PFS in the lenvatinib/pembrolizumab arm was 14.6 months versus 10.0 months in the placebo arm (HR 0.66; 95% CI 0.51–0.84; P=0.0002). PFS rate at 18 months was 39.1% versus 27.9%, respectively. Lenvatinib plus pembrolizumab also numerically favoured OS rate at 24 months over placebo: 74.6% versus 68.6% (HR 0.80; 95% CI 0.57–1.11; P=0.867). In addition, the objective response rate per mRECIST was significantly higher in the lenvatinib/pembrolizumab arm (71.3% vs 49.8%), as was the median duration of response (14.6 vs 12.5 months).

Grade 3 or 4 adverse events were more common in the lenvatinib/pembrolizumab arm than the placebo arm (71.3% vs 31.1%), as was treatment discontinuation (8.4% vs 1.2%).

Based on these outcomes, Prof. Llovet concluded that “treatment with lenvatinib plus pembrolizumab plus TACE may be a new option for patients with intermediate-stage HCC.”

1. Singal AG, et al. Hepatol. 2023;78:1922-1965.
2. Llovet JM, et al. Nat Rrev Gastroenterol Hepatol. 2021;18:293-313.
3. Kudo M, et al. Lancet 2018; 391:1163-1173.
4. Llovet JM, et al. Lancet Oncol 2023;24:1399-1410.
5. Llovet JM, et al. Transarterial chemoembolization (TACE) with or without lenvatinib (len) + pembrolizumab (pembro) for intermediate-stage hepatocellular carcinoma (HCC): Phase III LEAP-012 study. Abstract LBA3, ESMO Congress 2024, 13–17 September, Barcelona, Spain.

 

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Posted on 4 November 20244 November 2024