Thierry André and Jean-François Fléjou, Hôpital St Antoine; Thierry André and Jean-François Fléjou, University Pierre et Marie Curie Paris VI; Thierry André, Benoist Chibaudel, Annemilaï Tijeras-Raballand, Soudhir Colote, and Aimery de Gramont, Groupe Coopérateur Multdisciplinaire en Ocologie (GERCOR) Oncology Multidisciplinary Group and GERCOR-Innovative Research Consortium; Christophe Louvet, Institut Mutualiste Montsouris; Alex Duval, L'Institut National de la Santé et de la Recherche Médicale UMRS 938, Paris; Armand de Gramont, Benoist Chibaudel, Annemilaï, Tijeras Raballand, Aurelie Scriva, and Aimery de Gramont, Institut Hospitalier Franco Britannique, Levallois-Perret; Dewi Vernerey and Franck Bonnetain, Hôpital Saint-Jacques, Besançon; Christophe Tournigand, Hôpital Henri Mondor, Créteil, France; Armand de Gramont, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Tamas Hickish, Dorset Bournemouth University, Dorset, United Kingdom; Josep Tabernero and Stefania Landolfi, Vall d'Hebron University Hospital and Institute of Oncology, Barcelona; Josep Tabernero, TTD Group, Madrid, Spain; Jean Luc Van Laethem and Pieter Demetter, Hôpital Universitaire Erasme, Brussels, Belgium; Maria Banzi, Arcispedale Santa Maria Nuova, Reggio, Italy; Eduard Maartense, Reinier de Graaf Groep, Delft, the Netherlands; Einat Shmueli, Sheba Medical Center, Tel Hashomer, Israel; Goran U. Carlsson, Sahlgrenska University Hospital, Östra, Sweden; Werner Scheithauer, Medical University of Vienna, Vienna, Austria; Demetris Papamichael, B.O. Cyprus Oncology Centre, Nicosia, Cyprus; and Marcus Möehler, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany.
J Clin Oncol. 2015 Dec 10;33(35):4176-87. doi: 10.1200/JCO.2015.63.4238. Epub 2015 Nov 2.
PURPOSE: The MOSAIC (Multicenter International Study of Oxaliplatin/Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer) study has demonstrated 3-year disease-free survival (DFS) and 6-year overall survival (OS) benefit of adjuvant oxaliplatin in stage II to III resected colon cancer. This update presents 10-year OS and OS and DFS by mismatch repair (MMR) status and BRAF mutation. METHODS: Survival actualization after 10-year follow-up was performed in 2,246 patients with resected stage II to III colon cancer. We assessed MMR status and BRAF mutation in 1,008 formalin-fixed paraffin-embedded specimens. RESULTS: After a median follow-up of 9.5 years, 10-year OS rates in the bolus/infusional fluorouracil plus leucovorin (LV5FU2) and LV5FU2 plus oxaliplatin (FOLFOX4) arms were 67.1% versus 71.7% (hazard ratio [HR], 0.85; P = .043) in the whole population, 79.5% versus 78.4% for stage II (HR, 1.00; P = .980), and 59.0% versus 67.1% for stage III (HR, 0.80; P = .016) disease. Ninety-five patients (9.4%) had MMR-deficient (dMMR) tumors, and 94 (10.4%) had BRAF mutation. BRAF mutation was not prognostic for OS (P = .965), but dMMR was an independent prognostic factor (HR, 2.02; 95% CI, 1.15 to 3.55; P = .014). HRs for DFS and OS benefit in the FOLFOX4 arm were 0.48 (95% CI, 0.20 to 1.12) and 0.41 (95% CI, 0.16 to 1.07), respectively, in patients with stage II to III dMMR and 0.50 (95% CI, 0.25 to 1.00) and 0.66 (95% CI, 0.31 to 1.42), respectively, in those with BRAF mutation. CONCLUSION: The OS benefit of oxaliplatin-based adjuvant chemotherapy, increasing over time and with the disease severity, was confirmed at 10 years in patients with stage II to III colon cancer. These updated results support the use of FOLFOX in patients with stage III disease, including those with dMMR or BRAF mutation.
目的：MOSAIC（奥沙利铂/氟尿嘧啶/亚叶酸在结肠癌辅助治疗中的多中心国际研究）研究表明，在 II 期至 III 期可切除结肠癌中，辅助奥沙利铂可带来 3 年无病生存（DFS）和 6 年总生存（OS）获益。本研究更新了根据错配修复（MMR）状态和 BRAF 突变的 10 年 OS 和 OS 及 DFS 数据。
方法：对 2246 例 II 期至 III 期可切除结肠癌患者进行了 10 年随访后的生存实际情况评估。我们对 1008 例福尔马林固定石蜡包埋标本进行了 MMR 状态和 BRAF 突变检测。
结果：中位随访 9.5 年后，在总体人群中，接受氟尿嘧啶联合亚叶酸（LV5FU2）和 LV5FU2 联合奥沙利铂（FOLFOX4）治疗的 bolus/infusional 氟尿嘧啶组和 LV5FU2 加奥沙利铂组的 10 年 OS 率分别为 67.1%和 71.7%（风险比[HR]，0.85；P =.043），在 II 期疾病中分别为 79.5%和 78.4%（HR，1.00；P =.980），在 III 期疾病中分别为 59.0%和 67.1%（HR，0.80；P =.016）。95 例（9.4%）患者存在 MMR 缺陷（dMMR）肿瘤，94 例（10.4%）患者存在 BRAF 突变。BRAF 突变对 OS 无预后意义（P =.965），但 dMMR 是独立的预后因素（HR，2.02；95%CI，1.15 至 3.55；P =.014）。在 II 期至 III 期 dMMR 患者中，FOLFOX4 组的 DFS 和 OS 获益 HR 分别为 0.48（95%CI，0.20 至 1.12）和 0.41（95%CI，0.16 至 1.07），在 BRAF 突变患者中，DFS 和 OS 获益 HR 分别为 0.50（95%CI，0.25 至 1.00）和 0.66（95%CI，0.31 至 1.42）。
结论：在 II 期至 III 期结肠癌患者中，奥沙利铂为基础的辅助化疗的 OS 获益在 10 年时得到了证实，并且随着疾病严重程度的增加而增加。这些更新的结果支持在 III 期疾病患者中使用 FOLFOX，包括存在 dMMR 或 BRAF 突变的患者。
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