Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Sorafenib in Molecularly Selected Cancer Patients: Final Analysis of the MOST-Plus Sorafenib Cohort

Version 1 : Received: 15 May 2023 / Approved: 15 May 2023 / Online: 15 May 2023 (14:22:29 CEST)

A peer-reviewed article of this Preprint also exists.

Trédan, O.; Toulmonde, M.; Le Tourneau, C.; Montane, L.; Italiano, A.; Ray-Coquard, I.; De La Fouchardière, C.; Bertucci, F.; Gonçalves, A.; Gomez-Roca, C.; You, B.; Attignon, V.; Boyault, S.; Cassier, P.A.; Dufresne, A.; Tabone-Eglinger, S.; Viari, A.; Sohier, E.; Kamal, M.; Garin, G.; Blay, J.-Y.; Pérol, D. Sorafenib in Molecularly Selected Cancer Patients: Final Analysis of the MOST-Plus Sorafenib Cohort. Cancers 2023, 15, 3441. Trédan, O.; Toulmonde, M.; Le Tourneau, C.; Montane, L.; Italiano, A.; Ray-Coquard, I.; De La Fouchardière, C.; Bertucci, F.; Gonçalves, A.; Gomez-Roca, C.; You, B.; Attignon, V.; Boyault, S.; Cassier, P.A.; Dufresne, A.; Tabone-Eglinger, S.; Viari, A.; Sohier, E.; Kamal, M.; Garin, G.; Blay, J.-Y.; Pérol, D. Sorafenib in Molecularly Selected Cancer Patients: Final Analysis of the MOST-Plus Sorafenib Cohort. Cancers 2023, 15, 3441.

Abstract

Background: MOST-plus is a multicenter, randomized, open-label, adaptive Phase II trial evaluating the clinical benefit of targeted treatments matched to molecular alteration in advanced/metastatic solid tumors. Sorafenib was tested on patients with tumors harboring sorafenib-targeted genes Methods: The MOST-plus trial used a randomized discontinuation design. After 12 weeks of sorafenib (400 mg, po BID), patients with progressive disease dis-continued study, patients with objective response were proposed to continue sorafenib, whereas patients with stable disease (SD) were randomly assigned (1:1) to maintenance or interruption of treatment. Primary endpoint was RE-CIST version 1.1 progression-free rate at 16 weeks after randomization (PFR-16w). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Statistical analyses used a sequential Bayes-ian approach with interim efficacy analyses. The enrolment could be stopped in the case of a 95% probability for the estimated PFR-16w to be higher in the maintenance than in the interruption arm (NCT02029001). Results: 151 patients were included, of whom 35 had SD at 12 weeks of Soraf-enib. For the 35 patients with SD on sorafenib, the PFR-16w was 65% [95% credibility interval 43.4–83.7] in the continuation arm and 25% [7.8–48.1] in the interruption arm. Median PFS and OS were improved in maintenance versus interruption arm (mPFS: 5.6 [95%CI 1.97–6.77] months versus 2.0 [95%CI 1.61–3.91] months (p =0.0231) and mOS : 14.3 [95%CI 8.9–23.8] versus 8.0 months [95%CI 3.5–15.2] (p =0.0857)). Conclusion: Sorafenib showed activity in progressive patients with solid tu-mors harboring somatic genomic alterations in sorafenib-targeted genes. Con-tinuing sorafenib when SD is achieved improves PFR compared to interruption

Keywords

personalized medicine; biologically-driven trial; sorafenib; randomised discontinuation design

Subject

Public Health and Healthcare, Public Health and Health Services

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