Trédan Olivier, Toulmonde Maud, Le Tourneau Christophe, Montane Laure, Italiano Antoine, Ray-Coquard Isabelle, De La Fouchardière Christelle, Bertucci François, Gonçalves Anthony, Gomez-Roca Carlos, You Benoit, Attignon Valéry, Boyault Sandrine, Cassier Philippe A, Dufresne Armelle, Tabone-Eglinger Séverine, Viari Alain, Sohier Emilie, Kamal Maud, Garin Gwenaël, Blay Jean-Yves, Pérol David
Medical Oncology Department, Centre Léon Bérard, 69008 Lyon, France.
Inserm U1052, Centre de Recherche en Cancérologie de Lyon, F-69000 Lyon, France.
Cancers (Basel). 2023 Jun 30;15(13):3441. doi: 10.3390/cancers15133441.
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.
The MOST-plus trial used a randomized discontinuation design. After 12 weeks of sorafenib (400 mg, po BID), patients with progressive disease discontinued study, patients with objective response were proposed to continue sorafenib, whereas patients with stable disease (SD) were randomly assigned (1:1) to the maintenance or interruption of treatment. The primary endpoint was RECIST 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 Bayesian 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).
151 patients were included, of whom 35 had SD at 12 weeks of Sorafenib. 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 the maintenance versus the interruption arm (mPFS: 5.6 [95%CI 1.97-6.77] months versus 2.0 [95%CI 1.61-3.91] months ( = 0.0231) and mOS: 14.3 [95%CI 8.9-23.8] versus 8.0 months [95%CI 3.5-15.2] ( = 0.0857)).
Sorafenib showed activity in progressive patients with solid tumors harboring somatic genomic alterations in sorafenib-targeted genes. Continuing sorafenib when SD is achieved improves PFR compared to interruption.
MOST-plus是一项多中心、随机、开放标签的适应性II期试验，旨在评估针对晚期/转移性实体瘤分子改变的靶向治疗的临床益处。索拉非尼在携带索拉非尼靶向基因的肿瘤患者中进行了测试。
MOST-plus试验采用随机停药设计。在索拉非尼（400mg，口服，每日两次）治疗12周后，疾病进展的患者停止研究，有客观反应的患者继续使用索拉非尼，而疾病稳定（SD）的患者被随机分配（1:1）继续治疗或中断治疗。主要终点是随机分组后16周时的RECIST 1.1版无进展率（PFR-16w）。次要终点包括无进展生存期（PFS）、总生存期（OS）和毒性。统计分析采用序贯贝叶斯方法并进行中期疗效分析。如果估计的维持组PFR-16w高于中断组的概率为95%，则可停止入组（NCT02029001）。
共纳入151例患者，其中35例在索拉非尼治疗12周时疾病稳定。对于35例索拉非尼治疗后疾病稳定的患者，继续治疗组的PFR-16w为65%[95%可信区间43.4-83.7]，中断治疗组为25%[7.8-48.1]。维持组的中位PFS和OS较中断组有所改善（mPFS：5.6[95%CI 1.97-6.77]个月对2.0[95%CI 1.61-3.91]个月（P=0.0231），mOS：14.3[95%CI 8.9-23.8]对8.0个月[95%CI 3.5-15.2]（P=0.0857））。
索拉非尼在携带索拉非尼靶向基因体细胞基因组改变的实体瘤进展患者中显示出活性。与中断治疗相比，疾病稳定后继续使用索拉非尼可提高PFR。
