LBA79 - LENVAGIST: A multicentre, comparative, placebo (P)-controlled, double-blinded, phase II study of the efficacy of Lenvatinib (L) in patients with advanced GIST after failure of imatinib and sunitinib

Background

In advanced GIST, imatinib, then sunitinib, regorafenib and ripretinib are the usual sequence in 1^st, 2^nd, 3^rd and 4^th line, respectively. Beyond approved drugs, others tyrosine kinase inhibitors (TKI) can offer clinical benefit because some clones remain sensitive to TKI. L is a broad spectrum TKI (KIT, RET, PDGFRA, VEGFR 1-3, FGFR 1-4) approved in different solid tumors.

Methods

Eligible adult patients (pts) were randomly assigned (1:1) to receive L + best supportive care (BSC) or P+BSC (stratification on the number of prior drugs (2 vs ≥3)). Primary endpoint was Progression-Free Survival (PFS) based on investigator assessment. The study was designed to detect a hazard ratio (HR) of 0.5, translating in a 4-month PFS (PFS-4M) of 40% (L) versus 16% (P) with 10% 2-sided α error and 90% power. 74 pts (37/arm) were expected and 71 events were required for the final analysis. Main secondary endpoints included overall survival (OS), objective response rate and tolerance (NCI-CTC v5.0). Efficacy endpoints were assessed using the RECIST 1.1.

Results

From March 2020 to January 2024, 77 pts (L: 39, P: 38) were randomized. Median age was 65.0 y [23.0-85.0], 63.6% were males and 89.7% of pts have received ≥3 prior drugs. The intent-to-treat analysis showed an improved PFS with L vs P: PFS-4M of 39% (95% CI 23-54) vs 11% (95% CI 3-23) (HR: 0.44, 95% CI 0.27-0.71; stratified log-rank: p=0.0008). 2 partial responses were reported, both in L arm. 30 pts (79%) allocated to P switched to L (mPFS from L start 2.1 m (95%CI 0.9-3.7). With a median FU of 22.2 m, the median OS was 14.4 m (95%CI 7.1-18.9) for L vs 8.7 m (5.2-14.4) for P (HR: 0.77, 95% CI 0.46-1.28). Grade ≥3 related adverse events (AE) were reported in 22/39 pts (56.4%) with L vs 16/38 pts (42.1%) with P. Among all patients treated with L (n=69), 56.5% experienced related grade ≥3 AE (mainly hypertension: 40.6% and fatigue: 13%), 8.7% had investigator-related serious AE. 2 toxic deaths were reported by investigators.

Conclusions

The LENVAGIST study met its primary endpoint. Lenvatinib leads to clinical benefits in pts presenting advanced GIST after failure of available TKIs.

Clinical trial identification

Sponsor ID: ET18-291 NCT: 04193553 (release date Dec. 9th 2019).

Editorial acknowledgement

Legal entity responsible for the study

Centre Léon Bérard.

Funding

Eisai SAS.

Disclosure

O. Bouche: Financial Interests, Personal, Advisory Board: Amgen, Merck, Apmonia Therapeutics, Deciphera, Astellas, Takeda; Financial Interests, Personal, Invited Speaker: Servier, Pierre Fabre, Bayer. A. Dufresne: Non-Financial Interests, Project Lead, Translational research project: GSK, Adaptimmune; Non-Financial Interests, Project Lead, Translational research program: Bayer. L. Lebellec: Financial Interests, Personal, Invited Speaker: Astellas Pharma. D. Perol: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli-Lilly, Gilead, Ipsen, Pfizer, Novartis, Merck Sharp and Dohme, Roche, Takeda; Financial Interests, Personal, Advisory Board: Brenus Pharma; Other, travel expenses (ESMO annual meeting Madrid 2023): Novartis; Other, travel expenses (ESMO annual meeting Paris 2022): Roche. J. Blay: Financial Interests, Institutional, Research Funding: Eisai SAS. All other authors have declared no conflicts of interest.