Gordon Anderley, Cunningham David, Rajan Zayn, Fong Caroline, Peckitt Clare, Satchwell Laura, Cromarty Susan, Kidd Shannon, Piadel Katarzyna, Leamon Becky, Zhitkov Oleg, Davidson Michael, Thompson Joyce, Maisey Nicholas, Darby Suzanne, Waddell Tom, Morgan Carys, Bradshaw Alexander, Petty Russell, Fribbens Charlotte, Rao Sheela, Starling Naureen, Chau Ian
Gastrointestinal Unit, Department of Medicine, Royal Marsden Hospital, London and Surrey, United Kingdom.
Research Data & Statistics Unit, Royal Marsden Clinical Trials Unit, Royal Marsden Hospital, London and Surrey, United Kingdom.
JCO Oncol Adv. 2025 Apr 25;2(1):e2400073. doi: 10.1200/OA-24-00073. eCollection 2025.
PLATFORM is an adaptive phase II study assessing maintenance therapies in advanced esophagogastric adenocarcinoma (OGA). We evaluated the role of capecitabine plus a vascular endothelial growth factor receptor 2 inhibitor ramucirumab (cape-ram) in these patients.
Human epidermal growth factor receptor 2 (HER2)-negative patients with advanced OGA with stable or responding disease after 18 weeks of induction platinum-based chemotherapy were randomly assigned 1:1 to surveillance or cape-ram. The primary end point was progression-free survival (PFS), and key secondary end points were overall survival (OS) and safety. Recruitment to the cape-ram arm closed prematurely because of industry support withdrawal. A one-sided log-rank test with a 2.5% significance level was considered significant.
Between April 2019 and November 2022, 25 surveillance and 22 cape-ram patients were contemporaneously randomly assigned. Median follow-up was 24.4 months. Compared with surveillance, cape-ram significantly prolonged PFS (hazard ratio [HR], 0.33 [95% CI, 0.17 to 0.63], < .001; median PFS: 2.5 months with surveillance versus 5.5 months with cape-ram; 6-month PFS rate: 4% [95% CI, 0.3% to 17.0%] 42.9% [95% CI, 21.9% to 62.3%], respectively) and OS (HR, 0.51 [95% CI, 0.26 to 1.00], = .023; median OS: 7.1 months with surveillance 14.4 months with cape-ram; median OS from start of induction chemotherapy was 12.1 months 19.5 months, respectively). Of 10 cape-ram patients with measurable disease, 1 had an incremental partial response. Grade ≥3 adverse events (AEs) were seen in 32% surveillance and 57% cape-ram patients. Six cape-ram patients had grade 3 treatment-related AEs, and no new safety signals were identified.
Maintenance cape-ram after induction chemotherapy for patients with HER2-negative OGA significantly improved survival compared with surveillance. To our knowledge, this is the first randomized maintenance study demonstrating survival benefit and provides support for maintenance treatment.
PLATFORM是一项适应性II期研究，旨在评估晚期食管胃腺癌（OGA）的维持治疗。我们评估了卡培他滨联合血管内皮生长因子受体2抑制剂雷莫西尤单抗（卡培他滨-雷莫西尤单抗）在这些患者中的作用。
在接受18周铂类诱导化疗后病情稳定或有缓解的人表皮生长因子受体2（HER2）阴性晚期OGA患者中，以1:1的比例随机分配至观察或卡培他滨-雷莫西尤单抗组。主要终点是无进展生存期（PFS），关键次要终点是总生存期（OS）和安全性。由于行业支持撤回，卡培他滨-雷莫西尤单抗组的招募提前结束。采用单侧对数秩检验，显著性水平为2.5%。
2019年4月至2022年11月期间，同期随机分配了25例观察患者和22例卡培他滨-雷莫西尤单抗患者。中位随访时间为24.4个月。与观察相比，卡培他滨-雷莫西尤单抗显著延长了PFS（风险比[HR]，0.33[95%CI，0.17至0.63]，P<0.001；中位PFS：观察组为2.5个月，卡培他滨-雷莫西尤单抗组为5.5个月；6个月PFS率：分别为4%[95%CI，0.3%至17.0%]和42.9%[95%CI，21.9%至62.3%]）和OS（HR，0.51[95%CI，0.26至1.00]，P=0.023；中位OS：观察组为7.1个月，卡培他滨-雷莫西尤单抗组为14.4个月；从诱导化疗开始计算的中位OS分别为12.1个月和19.5个月）。在10例可测量疾病的卡培他滨-雷莫西尤单抗患者中，1例有递增的部分缓解。32%的观察患者和57%的卡培他滨-雷莫西尤单抗患者出现≥3级不良事件（AE）。6例卡培他滨-雷莫西尤单抗患者出现3级治疗相关AE，未发现新的安全信号。
对于HER2阴性OGA患者，诱导化疗后使用卡培他滨-雷莫西尤单抗维持治疗与观察相比显著提高了生存率。据我们所知，这是第一项证明生存获益的随机维持研究，并为维持治疗提供了支持。
