FIRE-3在592例KRAS外显子2野生型转移性结直肠癌(mCRC)患者中比较了FOLFIRI联合西妥昔单抗或贝伐单抗的一线治疗。共有分子亚组(CMS)根据CRC样品在四种不同亚型中的基因标记对其进行分组。CMS与mCRC治疗的相关性尚未确定。
在这个探索性分析中,根据以前发表的肿瘤CRC-CMSs对患者进行分组.采用卡方检验比较客观反应率(ORR)。使用Kaplan-Meier估计比较总生存期(OS)和无进展生存期(PFS)时间,对数秩测试。根据Cox比例风险方法估计风险比(HR)。
CMS分类可以在从意图治疗(ITT)群体获得的514个样本中的438个中确定(n=592)。其余438个样品的频率如下:CMS1(14%),CMS2(37%),CMS3(15%),CMS4(34%)。对于315个RAS野生型肿瘤,频率如下:CMS1(12%),CMS2(41%),CMS3(11%),CMS4(34%)。右侧与左侧原发性肿瘤的CMS分布如下:CMS1(27%对11%),CMS2(28%对45%),CMS3(10%对12%),CMS4(35%对32%)。独立于治疗,CMS是ORR的重要预后因素(P=0.051),PFS(P<0.001),OS(P<0.001)。在RAS野生型种群中,在CMS4中观察到的OS显着有利于FOLFIRI西妥昔单抗,而不是FOLFIRI贝伐单抗。在CMS3中,OS显示出有利于西妥昔单抗的趋势,而CMS1和CMS2的OS相当,与靶向治疗无关。
CMS分类是mCRC的预后。FIRE-3研究中FOLFIRI加西妥昔单抗与FOLFIRI加贝伐单抗诱导的OS延长似乎是由CMS3和CMS4驱动的。CMS分类为CRC的生物学提供了更深入的见解,但目前对临床决策没有直接影响。FIRE-3(AIOKRK-0306)研究已在ClinicalTrials.gov:NCT00433927注册。
FIRE-3 compared first-line therapy with FOLFIRI plus either cetuximab or bevacizumab in 592 KRAS exon 2 wild-type metastatic colorectal cancer (mCRC) patients. The
consensus molecular subgroups (
CMS) are grouping CRC samples according to their gene-signature in four different subtypes. Relevance of
CMS for the treatment of mCRC has yet to be defined.
In this exploratory analysis, patients were grouped according to the previously published tumor CRC-CMSs. Objective response rates (ORR) were compared using chi-square test. Overall survival (OS) and progression-free survival (PFS) times were compared using Kaplan-Meier estimation, log-rank tests. Hazard ratios (HR) were estimated according to the Cox proportional hazard method.
CMS classification could be determined in 438 out of 514 specimens available from the intent-to-treat (ITT) population (n = 592). Frequencies for the remaining 438 samples were as follows: CMS1 (14%), CMS2 (37%), CMS3 (15%), CMS4 (34%). For the 315 RAS wild-type tumors, frequencies were as follows: CMS1 (12%), CMS2 (41%), CMS3 (11%), CMS4 (34%).
CMS distribution in right- versus (vs) left-sided primary tumors was as follows: CMS1 (27% versus 11%), CMS2 (28% versus 45%), CMS3 (10% versus 12%), CMS4 (35% versus 32%). Independent of the treatment,
CMS was a strong prognostic factor for ORR (P = 0.051), PFS (P < 0.001), and OS (P < 0.001). Within the RAS wild-type population, OS observed in CMS4 significantly favored FOLFIRI cetuximab over FOLFIRI bevacizumab. In CMS3, OS showed a trend in favor of the cetuximab arm, while OS was comparable in CMS1 and CMS2, independent of targeted therapy.
CMS classification is prognostic for mCRC. Prolonged OS induced by FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab in the FIRE-3 study appears to be driven by CMS3 and CMS4. CMS classification provides deeper insights into the biology to CRC, but at present time has no direct impact on clinical decision-making.The FIRE-3 (AIO KRK-0306) study had been registered at ClinicalTrials.gov: NCT00433927.