Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Department of Medicine, Keio University Graduate School of Medicine, Tokyo, Japan.
Cancer Chemother Pharmacol. 2018 Jun;81(6):981-989. doi: 10.1007/s00280-018-3569-9. Epub 2018 Mar 29.
We conducted a systematic review and meta-analysis on survival impact of post-progression chemotherapy (post-Cx) after first-line chemotherapy (1st-Cx) and after second-line chemotherapy (2nd-Cx), and survival benefit of third-line chemotherapy (3rd-Cx) for advanced gastric cancer (AGC).
Phase III trials of systemic chemotherapy for AGC published in English between 2005 and 2015 or presented at annual meetings of ASCO or ESMO between 2013 and 2015 were searched. Numbers of patients, types of chemotherapy, patient baseline, proportion of patients receiving post-Cx (post-Cx%), median progression-free survival (mPFS), and median overall survival (mOS) of each treatment arm were surveyed; trials not reporting these parameters were excluded. Median post-progression survival (mPPS) was calculated as the difference between mOS and mPFS. Weighted Spearman's correlation coefficients between post-Cx% and survival outcomes (mOS and mPPS) were calculated. The effect of post-Cx% on survival outcomes adjusted for the types of chemotherapy and patient characteristics was evaluated by meta-regression.
Overall, 25 phase III trials of AGC were selected: 15 trials with 31 arms for 1st-Cx, and 10 trials with 16 arms for 2nd-Cx. Weighted Spearman's correlation coefficients for post-Cx% and mOS/mPPS were 0.520/0.739 for 1st-Cx, and 0.767/0.823 for 2nd-Cx. Meta-regression analyses adjusting for types of chemotherapy, age, and PS showed that a 10% increase in post-Cx% was associated with prolongation of mOS by 1.033 months for 1st-Cx and 0.344 months for 2nd-Cx.
Post-Cx% both after 1st-Cx and 2nd-Cx were correlated with mOS/mPPS, suggesting a survival benefit of 3rd-Cx in addition to that of 2nd-Cx for AGC.
我们对一线化疗（1 线化疗）和二线化疗（2 线化疗）后进展期化疗（post-Cx）对晚期胃癌（AGC）患者生存的影响以及三线化疗（3 线化疗）的生存获益进行了系统评价和荟萃分析。
检索了 2005 年至 2015 年期间发表的英文 3 期胃癌系统化疗试验，或 2013 年至 2015 年期间在 ASCO 或 ESMO 年会上报告的试验。调查了每个治疗组的患者人数、化疗类型、患者基线、接受 post-Cx（post-Cx%）的患者比例、中位无进展生存期（mPFS）和中位总生存期（mOS）；未报告这些参数的试验被排除在外。中位进展后生存期（mPPS）定义为 mOS 与 mPFS 之差。计算 post-Cx%与生存结局（mOS 和 mPPS）之间的加权斯皮尔曼相关系数。通过荟萃回归分析评估 post-Cx%对生存结局（化疗类型和患者特征调整后）的影响。
共纳入 25 项 AGC 的 3 期试验：15 项试验有 31 个 1 线化疗组，10 项试验有 16 个 2 线化疗组。post-Cx%与 mOS/mPPS 的加权斯皮尔曼相关系数分别为 1 线化疗 0.520/0.739 和 2 线化疗 0.767/0.823。调整化疗类型、年龄和 PS 后，meta 回归分析显示 post-Cx%每增加 10%，1 线化疗 mOS 延长 1.033 个月，2 线化疗 mOS 延长 0.344 个月。
1 线化疗和 2 线化疗后 post-Cx%均与 mOS/mPPS 相关，提示 AGC 患者在接受 2 线化疗的基础上接受 3 线化疗可进一步获益。
