精准医学试验颠覆了大规模随机对照试验的范式。病人的选择可能基于分子变异而不是原发肿瘤的位置。在小样本人群中，我们发展了生长调控指数（GMI）来评估治疗效果，通过将每个病人作为其自身的对照。FFCD 0307随机化三期试验比较了晚期胃癌中两种化疗序列的效果，这是一个独特的机会来评价GMI的相关性。在FFCD 0307试验中，晚期胃癌病人随机分为两种化疗序列（ECX后随着疾病进展转为FOLFIRI（A组），FOLFIRI后随着疾病进展转为ECX（B组））。GMI被定义为第二次治疗的无进展生存期（PFS2）与第一次治疗的进展时间（TTP1）的比值。序列效益被定义为GMI超过1.3（GMI高）。GMI与总生存期（OS）相关。OS1和OS2分别从第一次随机化和二线治疗失败到死亡进行测量。共有416名病人被随机分组（A组209人，B组207人）。175名病人（42%）接受了两种化疗序列，并进行了GMI评估（A组97人，B组79人）。A组中的中位数GMI要高于B组（0.62对0.47，P=0.04）。GMI高的病人的OS1较长（中位数14.9个月对11.5个月，不显著差异）。GMI高组的中位OS2增加一倍（3.4个月对1.6个月，不显著差异）。GMI分析提示ECX后随FOLFIRI可能比FOLFIRI后随ECX更好的治疗策略。高GMI与生存期延长有关。 版权所有 © 2023 作者。由Elsevier Ltd.出版。保留一切权利。

Precision medicine trials disrupted the paradigm of randomized controlled trials in large populations. Patient selection may be based on molecular alterations rather than on primary tumor location. In small patient populations, the growth modulation index (GMI) has been developed to evaluate treatment efficacy by using each patient as its own control. The FFCD 0307 randomized phase III trial compared two sequences of chemotherapy in advanced gastric cancer, which represents a unique opportunity to evaluate the relevance of the GMI.In the FFCD 0307 trial, patients with advanced gastric cancer were randomized between two chemotherapy sequences [ECX followed by FOLFIRI at disease progression (arm A) versus FOLFIRI followed by ECX (arm B)]. GMI was defined as the ratio of the progression-free survival on second treatment (PFS2) to the time to progression on first treatment (TTP1). Sequence benefit was defined as a GMI exceeding 1.3 (GMI-high). GMI was correlated with overall survival (OS). OS1 and OS2 were measured from first randomization and second-line failure to death.Four hundred and sixteen patients were randomized (209 in arm A, 207 in arm B). One hundred and seventy-five patients (42%) received the two sequences and were assessable for GMI (97 in arm A, 79 in arm B). The median GMI was higher in arm A than in arm B (0.62 versus 0.47, P = 0.04). Patients with a high GMI had a longer OS1 (median 14.9 versus 11.5 months, NS). Median OS2 was doubled in the GMI-high group (3.4 versus 1.6 months, NS).GMI analyses suggest that ECX followed by FOLFIRI might represent a better therapeutic strategy than FOLFIRI followed by ECX. High GMI was associated with prolonged survival.Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.