Ogata Takatsugu, Narita Yukiya, Wainberg Zev A, Van Cutsem Eric, Yamaguchi Kensei, Piao Yongzhe, Zhao Yumin, Peterson Patrick M, Wijayawardana Sameera R, Abada Paolo, Chatterjee Anindya, Muro Kei
Aichi Cancer Center Hospital, Nagoya, Japan.
University of California Los Angeles, Los Angeles, CA, United States.
J Gastric Cancer. 2023 Apr;23(2):289-302. doi: 10.5230/jgc.2023.23.e15.
Liver metastasis (LM) is reported in approximately 40% of patients with advanced/metastatic gastric/gastroesophageal junction adenocarcinoma (metastatic esophagogastric adenocarcinoma; mGEA) and is associated with a worse prognosis. This post-hoc analysis from the RAINBOW trial reported the efficacy, safety, and biomarker outcomes of ramucirumab and paclitaxel combination treatment (RAM+PAC) in patients with (LM+) and without (LM-) LM at baseline.
Patients (n=665) were randomly assigned on a 1:1 basis to receive either RAM+PAC (LM+: 150, LM-: 180) or placebo and paclitaxel (PL+PAC) (LM+: 138, LM-: 197). The overall survival (OS) and progression-free survival (PFS) were evaluated using stratified Kaplan-Meier and Cox regression models. The correlation of dichotomized biomarkers (VEGF-C, D; VEGFR-1,2) with efficacy in the LM+ versus LM- subgroups was analyzed using the Cox regression model with reported interaction P-values.
The presence of LM was associated with earlier progression than those without LM, particularly in patients receiving PL+PAC (hazard ratio [HR], 1.68). RAM+PAC treatment improved OS and PFS irrespective of LM status but showed greater improvement in LM+ than that in LM- (OS HR, 0.71 [LM+] vs. 0.88 [LM-]; PFS HR, 0.47 [LM+] vs. 0.76 [LM-]). Treatment-emergent adverse events were similar between patients with and without LM. No predictive relationship was observed between biomarker levels (VEGF-C, D; VEGFR-1,2) and efficacy outcome (OS, PFS) (all interaction P-values >0.05).
RAM provided a significant benefit, irrespective of LM status; however, its effect was numerically stronger in patients with LM. Therefore, RAM+PAC is a clinically meaningful therapeutic option for patients with mGEA and LM.
ClinicalTrials.gov Identifier: NCT01170663.
据报道，约40%的晚期/转移性胃/胃食管交界腺癌（转移性食管胃腺癌；mGEA）患者会发生肝转移（LM），且肝转移与较差的预后相关。RAINBOW试验的这项事后分析报告了雷莫西尤单抗和紫杉醇联合治疗（RAM+PAC）在基线时有肝转移（LM+）和无肝转移（LM-）的患者中的疗效、安全性及生物标志物结果。
患者（n=665）按1:1随机分配，分别接受RAM+PAC（LM+：150例，LM-：180例）或安慰剂加紫杉醇（PL+PAC）（LM+：138例，LM-：197例）。采用分层Kaplan-Meier法和Cox回归模型评估总生存期（OS）和无进展生存期（PFS）。使用Cox回归模型及报告的交互P值分析二分生物标志物（VEGF-C、D；VEGFR-1、2）与LM+和LM-亚组疗效的相关性。
与无肝转移的患者相比，肝转移的存在与更早的疾病进展相关，尤其是在接受PL+PAC治疗的患者中（风险比[HR]，1.68）。无论肝转移状态如何，RAM+PAC治疗均改善了OS和PFS，但在LM+患者中的改善程度大于LM-患者（OS HR，0.71[LM+]对0.88[LM-]；PFS HR，0.47[LM+]对0.76[LM-]）。有肝转移和无肝转移的患者之间治疗中出现的不良事件相似。未观察到生物标志物水平（VEGF-C、D；VEGFR-1、2）与疗效结果（OS、PFS）之间存在预测关系（所有交互P值>0.05）。
无论肝转移状态如何，雷莫西尤单抗均提供了显著益处；然而，其在肝转移患者中的效果在数值上更强。因此，RAM+PAC是mGEA和肝转移患者具有临床意义的治疗选择。
ClinicalTrials.gov标识符：NCT01170663。
