Department of Medical Oncology, Franco-British Hospital, Fondation Cognacq-Jay, Levallois-Perret, France; Fondation A.R.CA.D, Aide et Recherche en Cancérologie Digestive, Levallois-Perret, France; Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine (CRSA), Institut National de la Santé et de la Recherche Médicale (INSERM) U938, Institut Universitaire de Cancérologie (IUC), Faculté de Médecine, Sorbonne Université, Hôpital Saint-Antoine, Paris, France.
Department of Medical Oncology, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France.
Clin Colorectal Cancer. 2020 Sep;19(3):200-208.e1. doi: 10.1016/j.clcc.2020.02.012. Epub 2020 Mar 6.
We evaluated the prognostic value of KRAS and primary tumor location (PTL) for overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS) in metastatic colorectal cancer (mCRC).
Individual patient data from the DREAM phase III study were retrospectively analyzed. PTL was defined as right-sided or left-sided if tumor arising from the cecum to transverse colon or from the splenic flexure to the rectum, respectively. OS, PFS, and PPS were estimated using the Kaplan-Meier method and compared using log-rank test.
Among 700 patients included in the DREAM study, both PTL and KRAS were available for 536 (76.6%) patients. PTL showed stronger prognostic impact than KRAS status for OS (HR 1.62 vs. HR 1.37), PFS (HR 1.27 vs. HR 1.15) and PPS (HR 1.54 vs. HR 1.33). Interaction between PTL and KRAS was significant (P = .003). A negative impact of KRAS mutation was observed for OS and PPS, but not for PFS. Right-sided tumor was associated with poorer Eastern Cooperative Oncology Group performance status, anemia, and KRAS mutation, whereas left-sided KRAS wild-type tumor was associated with an increased lactate dehydrogenase. In patients with KRAS mutant mCRC, alkaline phosphatase was the main prognostic factor whatever the tumor site, whereas in those with KRAS wild-type tumors, prognostic factors varied according to PTL. The exposition to the anti-epidermal growth factor receptor (anti-EGFR) agents during and after study was similar in patients with left-sided and right-sided KRAS wild-type tumors.
Our findings suggest that a better prognosis of patients with mCRC with left-sided tumors is driven more strongly by PPS than by PFS when compared with patients with right-sided tumors, whatever the KRAS mutation status. This phenomenon was independent from the exposition to poststudy anti-EGFR monoclonal antibody.
我们评估了 KRAS 和原发肿瘤位置（PTL）对转移性结直肠癌（mCRC）总生存期（OS）、无进展生存期（PFS）和进展后生存期（PPS）的预后价值。
回顾性分析了 DREAM 三期研究的个体患者数据。PTL 定义为肿瘤起源于盲肠至横结肠或脾曲至直肠的右侧或左侧。OS、PFS 和 PPS 采用 Kaplan-Meier 法进行估计，并采用对数秩检验进行比较。
在 DREAM 研究纳入的 700 例患者中，536 例（76.6%）患者有 PTL 和 KRAS 资料。PTL 对 OS（HR 1.62 比 HR 1.37）、PFS（HR 1.27 比 HR 1.15）和 PPS（HR 1.54 比 HR 1.33）的预后影响强于 KRAS 状态。PTL 和 KRAS 之间存在显著的交互作用（P=0.003）。KRAS 突变对 OS 和 PPS 有负面影响，但对 PFS 没有影响。右侧肿瘤与较差的东部肿瘤协作组表现状态、贫血和 KRAS 突变有关，而左侧 KRAS 野生型肿瘤与乳酸脱氢酶升高有关。在 KRAS 突变型 mCRC 患者中，碱性磷酸酶是主要的预后因素，与肿瘤部位无关，而在 KRAS 野生型肿瘤患者中，预后因素则根据 PTL 而有所不同。在 KRAS 野生型左、右侧肿瘤患者中，在研究期间和之后暴露于抗表皮生长因子受体（anti-EGFR）药物的情况相似。
我们的研究结果表明，与右侧肿瘤患者相比，左侧肿瘤患者的 mCRC 具有更好的预后，这种预后更多地受到 PPS 的驱动，而不是 PFS，无论 KRAS 突变状态如何。这种现象独立于研究后抗 EGFR 单克隆抗体的暴露。
