Mansoor Wasat, Roeland Eric J, Chaudhry Aafia, Liepa Astra M, Wei Ran, Knoderer Holly, Abada Paolo, Chatterjee Anindya, Klempner Samuel J
The Christie NHS Foundation Trust, Manchester, United Kingdom.
Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA.
Oncologist. 2021 Sep;26(9):e1538-e1547. doi: 10.1002/onco.13836. Epub 2021 Jun 9.
Weight loss is common in advanced gastric and gastroesophageal junction adenocarcinoma (G/GEA); however, the prognostic implications of weight loss during the first cycle (C1) of chemotherapy remain poorly characterized. In this study, we investigated the impact of early weight loss during systemic treatment as a potential prognostic factor for overall survival (OS) in patients with advanced G/GEA.
We performed a post hoc analysis of three phase III studies of ramucirumab. Patients were categorized into two groups: weight loss of ≥3% and <3% based on weight change during C1 (3-4 weeks) of treatment. OS by weight groups was assessed for each study and as a pooled meta-analysis. The effect of C1 weight change on patient survival was evaluated using univariate and multivariate Cox models.
A total of 1,464 patients with weight data at the end of C1 were analyzed: REGARD (n = 311), RAINBOW (n = 591), and RAINFALL (n = 562). For all three studies, there were fewer patients in the weight loss ≥3% than <3% group. OS was numerically shorter for patients with weight loss of ≥3% than for patients with weight loss of <3% during C1 irrespective of treatment arm. Similar treatment independent effects of early weight loss on OS were observed in the meta-analysis. Overall, early weight loss ≥3% was associated with shorter survival in patients receiving active drug as well as placebo/best supportive care.
This large post hoc analysis demonstrated that weight loss of ≥3% during C1 was a negative prognostic factor for OS in patients with advanced G/GEA.
This comprehensive analysis examining early weight loss during systemic treatment as a predictor of survival outcomes in patients with advanced gastric and gastroesophageal junction adenocarcinoma (G/GEA) includes a large sample size, reliable on-treatment data reported in well-conducted phase III clinical trials, and global representation of cancer patients with advanced G/GEA. Understanding the impact of on-treatment weight loss is clinically relevant and may represent an opportunity for targeted interventions.
体重减轻在晚期胃癌和胃食管交界腺癌（G/GEA）中很常见；然而，化疗第一周期（C1）期间体重减轻的预后意义仍未得到充分描述。在本研究中，我们调查了全身治疗期间早期体重减轻作为晚期G/GEA患者总生存期（OS）潜在预后因素的影响。
我们对三项雷莫西尤单抗的III期研究进行了事后分析。根据治疗C1期（3 - 4周）期间的体重变化，将患者分为两组：体重减轻≥3%和<3%。对每项研究以及汇总的荟萃分析评估体重组的OS。使用单变量和多变量Cox模型评估C1期体重变化对患者生存的影响。
共分析了1464例在C1期末有体重数据的患者：REGARD研究（n = 311）、RAINBOW研究（n = 591）和RAINFALL研究（n = 562）。在所有三项研究中，体重减轻≥3%组的患者少于<3%组。无论治疗组如何，C1期体重减轻≥3%的患者的OS在数值上均短于体重减轻< 3%的患者。在荟萃分析中观察到早期体重减轻对OS有类似的与治疗无关的影响。总体而言，早期体重减轻≥3%与接受活性药物以及安慰剂/最佳支持治疗的患者生存期较短相关。
这项大型事后分析表明，C1期体重减轻≥3%是晚期G/GEA患者OS的不良预后因素。
这项综合分析将全身治疗期间的早期体重减轻作为晚期胃癌和胃食管交界腺癌（G/GEA）患者生存结果的预测指标，样本量大，来自精心开展的III期临床试验中可靠的治疗期间数据，且涵盖了晚期G/GEA癌症患者的全球情况。了解治疗期间体重减轻情况具有临床相关性，可能代表了进行靶向干预的机会。
