多西紫杉醇-奥沙利铂-卡培他滨/5-氟尿嘧啶（DOX/F）序贯多西紫杉醇对比奥沙利铂-卡培他滨/5-氟尿嘧啶（CAPOX/FOLFOX）在 HER2 阴性晚期胃癌中的应用。

Docetaxel-oxaliplatin-capecitabine/5-fluorouracil (DOX/F) followed by docetaxel versus oxaliplatin-capecitabine/5-fluorouracil (CAPOX/FOLFOX) in HER2-negative advanced gastric cancers.

机构信息

Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India.

Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.

出版信息

JNCI Cancer Spectr. 2024 Jul 1;8(4). doi: 10.1093/jncics/pkae054.

BACKGROUND

We evaluated whether the addition of docetaxel (D) to a combination comprising 5-fluorouracil/leucovorin (5-FU/LV) or capecitabine (C) plus oxaliplatin (O) (DOF/DOX) improved overall survival (OS) compared with 6 months of 5-fluorouracil (5-FU) or capecitabine in combination with oxaliplatin (FOLFOX/CAPOX) alone in advanced HER2-negative gastroesophageal junction and gastric adenocarcinomas (G/GEJ).

METHODS

This study was an investigator-initiated, open-label, multi-institutional, randomized phase III trial in adult patients with HER2-negative advanced G/GEJs. The primary endpoint of the study was a comparison of median OS by Kaplan-Meier method. Next-generation sequencing was performed on tissue.

RESULTS

Of the 324 patients randomly assigned between July 2020 and November 2022, 305 patients were evaluable for analysis (FOLFOX/CAPOX: 156; DOF/DOX: 149). With a median follow-up time of 19.2 months (95% Confidence Interval [CI] = 16.5 months to 21.9 months) for the entire cohort, the median OS was 10.1 months (95% CI = 9.2 to 10.9) for FOLFOX/CAPOX and 8.9 months (95% CI = 7.3 to 10.5) for DOF/DOX, and this difference was not statistically significant (P = .70). An increased proportion of grade 3 or grade 4 neutropenia (21% vs 3%; P < .001) and grade 2/3 neuropathy (17% vs 7%; P = .005) was seen in patients receiving DOF/DOX. Genomic profiling revealed a low incidence of microsatellite instability (1%) and a high incidence of BRCA1 (8.4%) and BRCA2 (7.5%) somatic alterations.

CONCLUSION

FOLFOX or CAPOX chemotherapy for 6 months remains one of the standards of care in advanced HER2-negative gastroesophageal junction and gastric adenocarcinomas, with no additional survival benefit seen with the addition of docetaxel. Genomic profiling of patients revealed a higher than previously known incidence of somatic BRCA alterations, which requires further evaluation.CTRI (Clinical Trial Registry of India: CTRI/2020/03/023944).

背景

我们评估了在晚期 HER2 阴性胃食管交界处和胃腺癌患者中，与单独使用奥沙利铂联合氟尿嘧啶/亚叶酸钙（FOLFOX/CAPOX）或卡培他滨（FOLFOX/CAPOX）相比，多西紫杉醇（D）联合氟尿嘧啶/亚叶酸钙（5-FU/LV）或卡培他滨（C）加奥沙利铂（O）（DOF/DOX）的组合是否能改善总生存期（OS）。

方法

这是一项由研究者发起的、开放性标签、多中心、随机 III 期临床试验，纳入了 HER2 阴性的晚期胃食管交界处和胃腺癌患者。该研究的主要终点是通过 Kaplan-Meier 方法比较中位 OS。对组织进行了下一代测序。

结果

在 2020 年 7 月至 2022 年 11 月期间随机分配的 324 例患者中，有 305 例患者可进行分析（FOLFOX/CAPOX：156 例；DOF/DOX：149 例）。在整个队列中，中位随访时间为 19.2 个月（95%置信区间[CI] = 16.5 个月至 21.9 个月），FOLFOX/CAPOX 的中位 OS 为 10.1 个月（95%CI = 9.2 至 10.9），DOF/DOX 为 8.9 个月（95%CI = 7.3 至 10.5），差异无统计学意义（P = 0.70）。接受 DOF/DOX 治疗的患者中，3 级或 4 级中性粒细胞减少症（21% vs 3%；P<0.001）和 2/3 级神经病变（17% vs 7%；P=0.005）的比例增加。基因组分析显示微卫星不稳定性的发生率较低（1%），BRCA1（8.4%）和 BRCA2（7.5%）体细胞改变的发生率较高。

结论

6 个月的 FOLFOX 或 CAPOX 化疗仍然是晚期 HER2 阴性胃食管交界处和胃腺癌的治疗标准之一，添加多西紫杉醇并没有带来额外的生存获益。对患者的基因组分析显示，体细胞 BRCA 改变的发生率高于先前已知的水平，这需要进一步评估。CTRI（印度临床试验注册中心：CTRI/2020/03/023944）。