没有研究明确证明化疗可以延长晚期食管癌的总生存期(OS)。我们对一线晚期不可切除/转移性食管/GEJ癌进行了III期随机研究。18-70岁的患者,表现状态为0-2,被随机分配到单独的最佳支持治疗(BSC),或BSC每周紫杉醇80mg/m2。BSC包括,如所示,教育,咨询,辐射,支架,饲管放置,营养补充,像镇痛药这样的药物,转诊到支持小组和姑息治疗。主要终点是OS;次要终点包括无进展生存期(PFS),回应,毒性,和QoL。2016年5月至2020年12月,我们招募了281例患者:143例接受化疗,138例接受BSC。269例(95.7%)患者的组织病理学为鳞状。紫杉醇剂量的中位数为12(IQR,7-23).BSC的中位OS为4.2个月(95%CI,3.42-5.32),化疗9.2个月(95%CI,8.02-10.48);HR,0.49(95%CI,0.39-0.64);p<.001。与BSC相比,化疗增加反应(2.9%至39%),中位PFS(2.1至4.2个月),1年OS(11%至32%),2年OS(0至9%),中位无吞咽困难生存期(2.9至14.8个月),以及全球和食道特异性QoL,没有显着增加所有等级或≥3级毒性。利用ESMO临床效益量表和ASCO价值框架,姑息性化疗评分为具有“实质性价值”。“我们的研究提供了第一个一级证据,证明化疗可以延长晚期食管癌/GEJ癌的生存期。仅BSC不再合适。每周紫杉醇是一个有吸引力的选择,特别是在获得免疫疗法有限的LMIC中。
No
study has unequivocally proven that chemotherapy prolongs overall survival (OS) in advanced esophageal cancer. We conducted a Phase III randomized
study in first-line advanced unresectable/metastatic esophageal/GEJ cancer. Patients aged 18-70 years, with performance status 0-2, were randomized to best supportive care (BSC) alone, or BSC with weekly paclitaxel 80 mg/m2. BSC comprised, as indicated, education, counselling, radiation, stenting, feeding tube placement, nutritional supplementation, medications like analgesics, and referral to a support group and palliative care. The primary endpoint was OS; secondary endpoints included progression free survival (PFS), response, toxicity, and QoL. Between May 2016-December 2020, we recruited 281 patients: 143 to chemotherapy and 138 to BSC. Histopathology was squamous in 269 (95.7%) patients. Median number of paclitaxel doses was 12 (IQR, 7-23). Median OS was 4.2 months (95% CI, 3.42-5.32) in BSC, and 9.2 months (95% CI, 8.02-10.48) in chemotherapy; HR, 0.49 (95% CI, 0.39-0.64); p < .001. As compared to BSC, chemotherapy increased response (2.9% to 39%), median PFS (2.1 to 4.2 months), 1-year OS (11% to 32%), 2-year OS (0 to 9%), median dysphagia-free survival (2.9 to 14.8 months), and global and esophagus-specific QoL, without significantly increasing all-grade or grade ≥3 toxicities. Using ESMO clinical benefit scale and ASCO Value Framework, palliative chemotherapy scored as having \"substantial value.\" Our
study provides the first level 1 evidence that chemotherapy prolongs survival in advanced esophageal/GEJ carcinoma. BSC alone is no longer appropriate. Weekly paclitaxel is an attractive option, especially in LMICs with limited access to immunotherapy.