背景:奧沙利鉑的計劃性停藥或停藥是 mCRC 係統治療的既定策略。因此，不管抗體使用情況如何，5FU/LV 代表了大多數維持策略的標準主幹。與 VEGF 靶向物質不同，EGFR 抗體對 RAS 野生型（RAS-WT）mCRC 患者 5FU/LV 維持有效的證據有限。
Background: Planned discontinuation or stop-and-go use of oxaliplatin are established strategies in the systemic therapy of mCRC. Consequently, and irrespective of antibody use, 5FU/LV represents the standard backbone of most maintenance strategies. Unlike VEGF-targeted substances, there is limited evidence that EGFR-antibodies add efficacy to 5FU/LV maintenance in RAS wildtype (RAS WT) mCRC patients.
方法：采用 5FU/LV、奧沙利鉑（FOLFOX）和 pmab 誘導治療 6 個周期，觀察其療效在 RAS-WT-mCRC 患者（pts）中，5FU/LV 聯合 pmab 與單獨 5FU/LV 的 1:1 隨機維持治療。主要終點是 PFS（無進展生存期：從隨機化到進展或死亡的時間）。由於 PFS 需要 218 個事件，本試驗旨在證明 5FU/LV+pmab 組與單獨 5FU/LV 組相比的優越性，危險比（HR）為 0.75，功率為 80%，顯著性水平為 10%。次要終點包括總生存率（OS）、對導入和維持治療的客觀反應以及生活質量。該試驗由 ClinicalTrials.gov 注冊，NCT01991873。
Methods: Following induction therapy with six cycles of 5FU/LV, oxaliplatin (FOLFOX) and pmab, the trial randomized maintenance therapy with 5FU/LV plus pmab vs. 5FU/LV alone in a 1:1 fashion in patients (pts) with RAS WT mCRC. The primary endpoint was PFS (progression-free survival: time from randomization until progression or death). With 218 events needed for PFS, the trial was designed to demonstrate superiority of the 5FU/LV+ pmab arm vs. 5FU/LV alone with a hazard ratio (HR) of 0.75, power of 80% and a significance level of 10%. Secondary endpoints included overall survival (OS), objective response to induction- and maintenance therapy as well as quality of life. The trial is registered with ClinicalTrials.gov, NCT01991873.
結果：全分析數據集包括 248 例患者（125 例 5FU/LV+pmab 和 123 例 5FU/LV）隨機分組接受維持治療。各試驗組（5FU/LV+pmab 與 5FU/LV）的中位年齡分別為 66 歲和 65 歲，男性患者分別為 69.6%和 63.4%，ecog0 分別為 56.8%和 60.2%。在數據截止時，218 個事件中，維持治療的 PFS 得到改善，5FU/LV+pmab 與單獨 5FU/LV 比較（8.8（80%CI 7.6-10.2）個月與 5.7（80%CI 5.6-6.0）個月，HR 0.72（80%CI 0.60-0.85），p=0.014）。OS（事件發生率 54.4%）在數值上傾向於 5FU/LV+pmab 組(28.7 個月(95% CI 25.4-39.1))，而單獨 5FU/LV 組(25.7 個月(95% CI22.2-28.2))，心率 0.84（95%可信區間 0.60-1.18）。
Results: The full analysis set consists of 248 pts (125 pts 5FU/LV + pmab and 123 pts 5FU/LV) who were randomized and received maintenance therapy. Median age was 66 vs. 65 years, male patients were 69.6% vs. 63.4%, ECOG 0 was 56.8% vs. 60.2% in the respective trial arms (5FU/LV+ pmab vs. 5FU/LV). At data cut-off, with 218 events, PFS of maintenance therapy was improved with 5FU/LV+ pmab vs. 5FU/LV alone (8.8 (80% CI 7.6-10.2) months vs. 5.7 (80% CI 5.6-6.0) months, HR 0.72 (80%CI 0.60-0.85), p = 0.014). OS (event rate 54.4%) numerically favoured the 5FU/LV+ pmab arm (28.7 (95% CI 25.4-39.1) months) as compared to 5FU/LV alone (25.7 (95% CI 22.2-28.2) months), HR 0.84 (95% CI 0.60-1.18).
結論：在 RAS-WTmCRC 中， 5FU/LV+pmab 維持治療優於單用 5FU/LV ，應作為 FOLFOX-pluspmab 誘導治療後的標準護理維持方案。
Conclusion: In RAS WT mCRC, maintenance therapy with 5FU/LV+ pmab appears to be superior to 5FU/LV alone and should be regarded as standard of care maintenance regimen following induction therapy with FOLFOX plus pmab.
