touchONCOLOGY coverage of data presented at European Society of Medical Oncology (ESMO) 2024 Annual Congress
The LEAP-012 trial is a phase III, randomized, double-blind study that evaluated the efficacy and safety of combining lenvatinib and pembrolizumab with transarterial chemoembolization (TACE) compared to placebo plus TACE in patients with intermediate-stage hepatocellular carcinoma (HCC). The study found that lenvatinib + pembrolizumab + TACE significantly improved progression-free survival (PFS) compared to placebo + TACE, with a median PFS of 14.6 months versus 10.0 months. However, overall survival (OS) was not statistically significant at the time of analysis. Treatment-related adverse events (TRAEs) were higher in the lenalidomide + pembrolizumab group versus placebo (71.3% versus 31.5%). The combination therapy showed a promising improvement in PFS, though further analysis is needed to confirm the OS benefit.
The late-breaking abstract, ‘Transarterial chemoembolization (TACE) with or without lenvatinib (len) + pembrolizumab (pembro) for intermediate-stage hepatocellular carcinoma (HCC): Phase III LEAP-012 study’ (LBA3) was presented at the European Society of Medical Oncology Congress 2024 on 13–17 September 2024 in Barcelona, Spain.
Disclosures: Prof. Josep Llovet discloses that he has acted as a consultant for Eisai Inc., Merck, Roche, Genentech, Astrazeneca, Bayer Pharmaceuticals, Abbvie, Sanofi, Moderna, Glycotest and Exelixis; has received grant/research support from Eisai Inc. and Bayer Pharmaceuticals; and has served on an advisory board for Bristol Myers Squibb.
This content has been developed independently by Touch Medical Media for touchONCOLOGY. It is not affiliated with the European Society of Medical Oncology (ESMO). Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Transcript
I’m Josep Llovet. I’m Professor of Medicine and Director of the liver cancer program at Mount Sinai, New York. I’m also Professor of Medicine at the Hospital Clinic, University of Barcelona, IDIBAPS, in Barcelona.
LEAP-012 phase III study: transarterial chemoembolization ± lenvatinib + pembrolizumab for immediate-stage hepatocellular carcinoma
This year at ESMO we presented the LEAP-012 study, aimed to compare lenvatinib plus pembrolizumab plus TACE versus TACE in patients with intermediate HCC. Intermediate HCC represents 30% of patients with HCC that currently are treated with transarterial chemoembolization. This has been the standard of care for the last 20 years. Modern randomized controlled trials in this area have tested combinations of systemic therapies with TACE, and unfortunately they resulted in negative outcomes.
We designed this study with 480 patients that were randomized 1:1 to receive lenvatinib plus pembrolizumab for 3 years+ days versus dual placebo plus days. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoint was objective response rate (ORR). We hit the primary endpoint of PFS with median PFS for the combo arm of 14.5 months and for the dual placebo phase arm of 10 months, with a hazard ratio of 0.66 and a p-value of 0.0002. This profound effect in PFS was also reiterated in the specified subgroup analysis. Regarding the other primary endpoint of OS, here we presented the first interim analysis with 151 events, and there was a trend favoring lenvatinib-pembrolizumab dose with a hazard ratio of 0.8 and p-value of 0.086. We also checked the ORR as measured by myelofibrosis, following the American and European guidelines, and the ORRs for the combination of systemic therapies was 72%, 56% of which represented complete responses, which is an outstanding landmark compared to overall a 49% ORR for the dual placebo arm.
In terms of adverse events, treatment-related adverse events accounted for 71% in the combo arm and 31% in the dual placebo TACE arm, related directly to transarterial chemoembolization. The most common were hypertension, proteinuria, increased LTST, hypothyroidism and also post-embolization syndrome related directly to TACE. Treatment-related adverse events leading to discontinuation of both lenvatinib plus pembrolizumab accounted for 80% of the patients and grade 5 toxicity accounted for 1.7%.
Overall, taking into account the three variables of efficacy, the two primary endpoints of PFS and objective response, and also that the safety profile was manageable and there were no new treatment-related adverse events as opposed to the ones already reported. We support the treatment of lenvatinib plus pembrolizumab plus TACE as the newest standard of care for patients at the intermediate hepatocellular carcinoma.
Thank you very much for your attention.
Interviewer/Editor: Nicola Cartridge
Cite: Llovet J. TACE with lenvatinib and pembrolizumab for hepatocellular carcinoma. touchONCOLOGY. September 26, 2024.
Abbreviations: HCC: hepatocellular carcinoma; OS: overall survival; overall response rate (ORR); PFS: progression-free survival; TACE: transarterial chemoembolization; TRAEs: Treatment-related adverse events
