Department of Gastroenterology, Cochin Hospital, Paris, France.
Department of Oncology, Institut Sainte Catherine, Avignon, France.
Oncologist. 2020 Feb;25(2):e266-e275. doi: 10.1634/theoncologist.2019-0328. Epub 2019 Oct 2.
Patients with RAS wild-type (WT) nonresectable metastatic colorectal cancer (mCRC) may receive either bevacizumab or an anti-epidermal growth factor receptor (EGFR) combined with first-line, 5-fluorouracil-based chemotherapy. Without the RAS status information, the oncologist can either start chemotherapy with bevacizumab or wait for the introduction of the anti-EGFR. Our objective was to compare both strategies in a routine practice setting.
This multicenter, retrospective, propensity score-weighted study included patients with a RAS WT nonresectable mCRC, treated between 2013 and 2016 by a 5-FU-based chemotherapy, with either delayed anti-EGFR or immediate anti-vascular endothelial growth factor (VEGF). Primary criterion was overall survival (OS). Secondary criteria were progression-free survival (PFS) and objective response rate (ORR).
A total of 262 patients (129 in the anti-VEGF group and 133 in the anti-EGFR group) were included. Patients receiving an anti-VEGF were more often men (68% vs. 56%), with more metastatic sites (>2 sites: 15% vs. 9%). The median delay to obtain the RAS status was 19 days (interquartile range: 13-26). Median OS was not significantly different in the two groups (29 vs. 30.5 months, p = .299), even after weighting on the propensity score (hazard ratio [HR] = 0.86, 95% confidence interval [CI], 0.69-1.08, p = .2024). The delayed introduction of anti-EGFR was associated with better median PFS (13.8 vs. 11.0 months, p = .0244), even after weighting on the propensity score (HR = 0.74, 95% CI, 0.61-0.90, p = .0024). ORR was significantly higher in the anti-EGFR group (66.7% vs. 45.6%, p = .0007).
Delayed introduction of anti-EGFR had no deleterious effect on OS, PFS, and ORR, compared with doublet chemotherapy with anti-VEGF.
For RAS/RAF wild-type metastatic colorectal cancer, patients may receive 5-fluorouracil-based chemotherapy plus either bevacizumab or an anti-epidermal growth factor receptor (EGFR). In daily practice, the time to obtain the RAS status might be long enough to consider two options: to start the chemotherapy with bevacizumab, or to start without a targeted therapy and to add the anti-EGFR at reception of the RAS status. This study found no deleterious effect of the delayed introduction of an anti-EGFR on survival, compared with the introduction of an anti-vascular endothelial growth factor from cycle 1. It is possible to wait one or two cycles to introduce the anti-EGFR while waiting for RAS status.
RAS 野生型（WT）不可切除转移性结直肠癌（mCRC）患者可接受贝伐珠单抗或抗表皮生长因子受体（EGFR）联合一线基于 5-氟尿嘧啶的化疗。如果没有 RAS 状态信息，肿瘤学家可以开始贝伐珠单抗联合化疗，或者等待引入抗 EGFR。我们的目的是在常规实践环境中比较这两种策略。
这项多中心、回顾性、倾向评分加权研究纳入了 2013 年至 2016 年间接受基于 5-氟尿嘧啶的化疗治疗的 RAS WT 不可切除 mCRC 患者，他们接受了延迟抗 EGFR 或立即抗血管内皮生长因子（VEGF）治疗。主要标准是总生存期（OS）。次要标准是无进展生存期（PFS）和客观缓解率（ORR）。
共纳入 262 例患者（抗 VEGF 组 129 例，抗 EGFR 组 133 例）。接受抗 VEGF 治疗的患者中，男性（68%比 56%）和转移部位较多（>2 个部位：15%比 9%）。获得 RAS 状态的中位延迟时间为 19 天（四分位距：13-26）。两组的中位 OS 无显著差异（29 个月比 30.5 个月，p=0.299），即使在倾向评分加权后（风险比[HR]=0.86，95%置信区间[CI]，0.69-1.08，p=0.2024）。延迟引入抗 EGFR 与中位 PFS 延长相关（13.8 个月比 11.0 个月，p=0.0244），即使在倾向评分加权后（HR=0.74，95%CI，0.61-0.90，p=0.0024）。抗 EGFR 组的 ORR 明显更高（66.7%比 45.6%，p=0.0007）。
与贝伐珠单抗联合化疗相比，延迟引入抗 EGFR 对 OS、PFS 和 ORR 没有不良影响。
对于 RAS/RAF 野生型转移性结直肠癌，患者可接受基于 5-氟尿嘧啶的化疗联合贝伐珠单抗或抗表皮生长因子受体（EGFR）治疗。在日常实践中，获得 RAS 状态的时间可能足够长，可以考虑两种选择：开始使用贝伐珠单抗的化疗，或在没有靶向治疗的情况下开始化疗，并在获得 RAS 状态时添加抗 EGFR。与第 1 周期引入抗血管内皮生长因子相比，本研究发现延迟引入抗 EGFR 对生存没有不良影响。在等待 RAS 状态的同时，等待一个或两个周期引入抗 EGFR 是可能的。
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