Cremolini C, Antoniotti C, Lonardi S, Bergamo F, Cortesi E, Tomasello G, Moretto R, Ronzoni M, Racca P, Loupakis F, Zaniboni A, Tonini G, Buonadonna A, Marmorino F, Allegrini G, Granetto C, Masi G, Zagonel V, Sensi E, Fontanini G, Boni L, Falcone A
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Ann Oncol. 2018 Jul;29(7):1528-1534. doi: 10.1093/annonc/mdy140. Epub 2018 Apr 20.
Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status.
Patients were randomized to receive upfront 5-fluoruracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab or 5-fluoruracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab. Tumors were defined as right- or left-sided if they originated from the caecum to the transverse colon or within the splenic flexure and beyond, respectively. Patients with available information about both primary sidedness and RAS and BRAF status were included in the present analysis. Progression-free survival (PFS), overall survival (OS) and RECIST response rate were assessed according to tumor location and RAS and BRAF mutational status.
Information about primary sidedness and RAS and BRAF status was available for 358 (70.5%) out of 508 randomized patients. Patients with right-sided tumors (N = 173) presented shorter OS [23.7 versus 31.0 months, HR = 1.42 (95% CI 1.09-1.84), P = 0.010] and a trend toward shorter PFS [10.2 versus 11.5 months, HR = 1.24 (95% CI: 0.98-1.56), P = 0.083] than those with left-sided tumors (N = 185), but these associations were no longer evident when adjusting for RAS and BRAF status. Patients with right-sided tumors achieved more relative benefit from the intensification of the chemotherapy backbone in terms of both PFS (HR = 0.59 versus 0.89, P for interaction = 0.099) and OS (HR = 0.56 versus 0.99, P for interaction = 0.030) and this advantage was independent of their RAS and BRAF status.
FOLFOXIRI plus bevacizumab may be regarded as a preferred first-line treatment option for clinically selected patients with right-sided metastatic colorectal cancer irrespective of their RAS and BRAF mutational status. Trial registration: clinicaltrials.gov identifier NCT00719797.
右侧转移性结直肠癌（mCRC）患者预后较差，一线双联化疗方案联合靶向药物的获益有限。在这项TRIBE研究的非计划分析中，我们调查了原发性肿瘤部位对mCRC患者的预后和预测影响，以及在根据原发性肿瘤部位以及RAS和BRAF突变状态定义的亚组中强化化疗的不同影响。
患者被随机分配接受初始的5-氟尿嘧啶、亚叶酸钙和伊立替康（FOLFIRI）联合贝伐单抗，或5-氟尿嘧啶、亚叶酸钙、奥沙利铂和伊立替康（FOLFOXIRI）联合贝伐单抗。如果肿瘤分别起源于盲肠至横结肠或脾曲及更远部位，则定义为右侧或左侧肿瘤。本分析纳入了具有原发性肿瘤部位以及RAS和BRAF状态可用信息的患者。根据肿瘤位置以及RAS和BRAF突变状态评估无进展生存期（PFS）、总生存期（OS）和RECIST缓解率。
508例随机分组患者中，358例（70.5%）有原发性肿瘤部位以及RAS和BRAF状态的信息。右侧肿瘤患者（N = 173）的OS较短[23.7个月对31.0个月，HR = 1.42（95%CI 1.09 - 1.84），P = 0.010]，PFS有缩短趋势[10.2个月对11.5个月，HR = 1.24（95%CI：0.98 - 1.56），P = 0.083]，低于左侧肿瘤患者（N = 185），但在调整RAS和BRAF状态后，这些关联不再明显。右侧肿瘤患者在化疗方案强化方面，在PFS（HR = 0.59对0.89，交互作用P = 0.099）和OS（HR = 0.56对0.99，交互作用P = 0.030）方面获得了更多相对获益，且这一优势与其RAS和BRAF状态无关。
无论RAS和BRAF突变状态如何，FOLFOXIRI联合贝伐单抗可被视为临床选择的右侧转移性结直肠癌患者的首选一线治疗方案。试验注册：clinicaltrials.gov标识符NCT00719797。
