Fong C, Patel B, Peckitt C, Bourmpaki E, Satchwell L, Cromarty S, Kidd S, von Loga K, Uhlik M, Begum R, Rana T, Waddell T, Darby S, Bradshaw A, Roques T, Morgan C, Rees C, Herbertson R, Das P, Thompson C, Hewish M, Petty R, Thistlethwaite F, Rao S, Starling N, Chau I, Cunningham D
Gastrointestinal Unit, Department of Medicine, Royal Marsden Hospital, London and Surrey.
Research Data & Statistics Unit, Royal Marsden Clinical Trials Unit, Royal Marsden Hospital, London and Surrey.
ESMO Open. 2024 Jul;9(7):103622. doi: 10.1016/j.esmoop.2024.103622. Epub 2024 Jul 13.
PLAnning Treatment For Oesophago-gastric Cancer: a Randomised Maintenance Therapy Trial (PLATFORM) is an adaptive phase II study assessing the role of maintenance therapies in advanced oesophago-gastric (OG) adenocarcinoma. We evaluated the role of the anti-programmed death-ligand 1 (PD-L1) inhibitor durvalumab in these patients.
Patients with human epidermal growth factor receptor 2-negative locally advanced or metastatic OG adenocarcinoma with disease control or response to 18 weeks of platinum-based first-line chemotherapy were randomised to active surveillance or maintenance durvalumab. The primary endpoint was progression-free survival (PFS). Safety was assessed in all patients who had commenced surveillance visits or received at least one dose of durvalumab. Exploratory survival analyses according to PD-L1 Combined Positive Score (CPS) and immune (biomarker-positive) or angiogenesis dominant (biomarker-negative) tumour microenvironment (TME) phenotypes were conducted.
Between March 2015 and April 2020, 205 patients were randomised to surveillance (n = 100) and durvalumab (n = 105). No significant differences were seen in PFS [hazard ratio (HR) 0.84, P = 0.13] and overall survival (OS; HR 0.98, P = 0.45) between surveillance and durvalumab. Five patients randomised to durvalumab demonstrated incremental radiological responses compared with none with surveillance. Treatment-related adverse events occurred in 77 (76.2%) durvalumab-assigned patients. A favourable effect in OS with durvalumab over surveillance in CPS ≥5 and immune biomarker-positive patients was observed compared with CPS <5 and biomarker-negative subgroups, respectively: CPS ≥5 versus <5: HR 0.63, 95% confidence interval (CI) 0.32-1.22 versus HR 0.93, 95% CI 0.44-1.96; biomarker-positive versus negative: HR 0.60, 95% CI 0.29-1.23 versus HR 0.84, 95% CI 0.42-1.65.
Maintenance durvalumab does not improve PFS in patients with OG adenocarcinoma who respond to first-line chemotherapy but induced incremental radiological responses in a subset of patients. TME characterisation could refine patient selection for anti-PD-L1 therapy above PD-L1 CPS alone.
食管癌-胃癌治疗方案规划：一项随机维持治疗试验（PLATFORM）是一项适应性II期研究，评估维持治疗在晚期食管-胃（OG）腺癌中的作用。我们评估了抗程序性死亡配体1（PD-L1）抑制剂度伐利尤单抗在这些患者中的作用。
人表皮生长因子受体2阴性的局部晚期或转移性OG腺癌患者，疾病得到控制或对18周的铂类一线化疗有反应，被随机分配至主动监测组或度伐利尤单抗维持治疗组。主要终点是无进展生存期（PFS）。对所有开始监测访视或接受至少一剂度伐利尤单抗的患者进行安全性评估。根据PD-L1联合阳性评分（CPS）以及免疫（生物标志物阳性）或血管生成主导（生物标志物阴性）肿瘤微环境（TME）表型进行探索性生存分析。
2015年3月至2020年4月期间，205例患者被随机分配至监测组（n = 100）和度伐利尤单抗组（n = 105）。监测组和度伐利尤单抗组在PFS[风险比（HR）0.84，P = 0.13]和总生存期（OS；HR 0.98，P = 0.45）方面未见显著差异。随机分配至度伐利尤单抗组的5例患者显示出影像学反应增强，而监测组无此情况。77例（76.2%）接受度伐利尤单抗治疗的患者发生了与治疗相关的不良事件。与CPS<5和生物标志物阴性亚组相比，分别观察到度伐利尤单抗在CPS≥5和免疫生物标志物阳性患者的OS方面比监测组有更有利的效果：CPS≥5与<5：HR 0.63，95%置信区间（CI）0.32 - 1.22对比HR 0.93，95%CI 0.44 - 1.96；生物标志物阳性与阴性：HR 0.60，95%CI 0.29 - 1.23对比HR 0.84，95%CI 0.42 - 1.65。
维持使用度伐利尤单抗并不能改善对一线化疗有反应的OG腺癌患者的PFS，但在一部分患者中诱导了影像学反应增强。TME特征描述可优化单纯基于PD-L1 CPS之上的抗PD-L1治疗的患者选择。
