福克斯
医学
阿替唑单抗
微卫星不稳定性
肿瘤科
内科学
结直肠癌
耐受性
临床终点
危险系数
无容量
癌症
随机对照试验
奥沙利铂
免疫疗法
不利影响
置信区间
化学
等位基因
基因
微卫星
生物化学
作者
Frank A. Sinicrope,Fang‐Shu Ou,Qian Shi,Andrew B. Nixon,Kabir Mody,Alain Levasseur,Amylou C. Dueck,Asha Dhanarajan,Christopher H. Lieu,Deirdre Jill Cohen,Federico Innocenti,Robert J. Behrens,Walter R. Peters,Daniel J. Sargent,Nicolas Sommer,Eileen Mary O'Reilly,Jeffrey A. Meyerhardt
标识
DOI:10.1200/jco.2017.35.15_suppl.tps3630
摘要
TPS3630 Background: In metastatic colorectal cancer with deficient DNA mismatch repair (MMR), anti-PD-1 antibody monotherapy produced high tumor response rates and extended progression-free survival compared to lack of benefit for proficient MMR tumors (Le, M, et al, NEJM 2016). We propose a phase III randomized trial to determine if the addition of the anti-PD-L1 antibody, atezolizumab (Genentech™), to adjuvant FOLFOX can improve patient disease-free survival (DFS) vs FOLFOX alone in patients with stage III colon cancers with dMMR or microsatellite instability (MSI). By blocking the PD-1/PD-L1 interaction, atezolizumab may activate T cells, thereby, restoring their ability to detect and attack tumor cells. Limited data suggest that FOLFOX may increase intratumoral cytotoxic CD8+ T cells that may serve as ‘immune priming.’ Methods: Patients with curatively resected stage III colon carcinomas with evidence of dMMR or MSI will be randomized to modified FOLFOX6 for 6 months (12 cycles) alone or combined with atezolizumab (840 mg IV q2 wk) continued as monotherapy for an additional 6 months (total duration of 12 months). Patients will be stratified by T, N stage and tumor sidedness. Local testing for MSI or MMR proteins is allowed. Atezolizumab must begin by/with cycle 2. The targeted accrual goal of 700 patients provides 90% power to detect an effect size expressed as hazard ratio of 0.6 for the primary endpoint DFS at two-sided alpha of 0.05. Interim analyses are planned at 50% and 75% of events. Secondary endpoints include overall survival, treatment tolerability, and quality of life. This study will be conducted by the Alliance for Clinical Trials in Oncology. The protocol has been approved by NCI CTEP and is expected to be activated in mid 2017. Clinical trial information: NCT02912559.
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