Antoniotti Carlotta, Germani Marco M, Rossini Daniele, Lonardi Sara, Pietrantonio Filippo, Santini Daniele, Marmorino Federica, Allegrini Giacomo, Daniel Francesca, Raimondi Alessandra, Borelli Beatrice, Zaniboni Alberto, Conca Veronica, Abraham Jim, Spetzler David, Maiello Evaristo, Boccaccino Alessandra, Passardi Alessandro, Giordano Mirella, Tamburini Emiliano, Korn Michael W, Masi Gianluca, Cremolini Chiara
Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy; Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Medical Oncology Unit 3, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.
Eur J Cancer. 2022 May;167:23-31. doi: 10.1016/j.ejca.2022.02.031. Epub 2022 Mar 30.
We performed a pooled analysis of TRIBE and TRIBE2 studies to assess the efficacy and safety of the intensification of upfront chemotherapy backbone - from doublets to the triplet FOLFOXIRI - in combination with bevacizumab (bev) in patients with early-onset metastatic colorectal cancer (EO-mCRC; aged <50 years) and to explore whether EO-mCRCs have a peculiar tumour genomic profiling.
Subgroup analyses according to age (<50 versus ≥50 years) and treatment (FOLFOXIRI/bev versus doublets/bev) were carried out for rates of any grade and grade ≥3 (≥G3) overall and singular adverse events, progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). Tumour genomic profiling was obtained using a DNA-based next-generation sequencing platform.
Of 1187 patients included, 194 (16%) patients were aged <50 years. Females were more frequently diagnosed with EO-mCRC (P = 0.04). Patients aged <50 years showed a lower risk of ≥G3 neutropenia (P = 0.07), diarrhoea (P = 0.04), asthenia (P = 0.008) and a higher risk of any grade nausea (P < 0.01) and vomiting (P < 0.01). Patients receiving FOLFOXIRI/bev more frequently experienced ≥G3 chemotherapy-related adverse events respect to doublets/bev, regardless of age (P = 0.60). FOLFOXIRI/bev was associated to a lower incidence of neutropenia (P = 0.04) and asthenia (P = 0.01) in patients <50 years old, than those aged ≥50 years. PFS, OS and ORR did not differ according to age (PFS P = 0.81, OS P = 0.44, ORR P = 0.50) and no interaction between age and the benefit from the intensification of upfront chemotherapy was observed (PFS P = 0.72, OS P = 0.54, ORR P = 0.65). Genomic profiling was assessed in 296 patients, showing an enrichment of FBXW7 and POLE mutations in EO-mCRC.
Upfront FOLFOXIRI/bev shows a favourable efficacy/safety balance in EO-mCRC.
Clinicaltrials.gov Identifiers NCT00719797, NCT0233-9116.
我们对TRIBE和TRIBE2研究进行了汇总分析，以评估在早期转移性结直肠癌（EO-mCRC；年龄<50岁）患者中，将初始化疗主干方案从双药方案强化为三联方案FOLFOXIRI并联合贝伐单抗（bev）的疗效和安全性，并探讨EO-mCRC是否具有独特的肿瘤基因组特征。
根据年龄（<50岁与≥50岁）和治疗方案（FOLFOXIRI/bev与双药方案/bev）进行亚组分析，以评估所有级别和≥3级（≥G3）总体及单项不良事件的发生率、无进展生存期（PFS）、总生存期（OS）和客观缓解率（ORR）。使用基于DNA的下一代测序平台进行肿瘤基因组特征分析。
在纳入的1187例患者中，194例（16%）年龄<50岁。女性更常被诊断为EO-mCRC（P = 0.04）。年龄<50岁的患者发生≥G3级中性粒细胞减少症（P = 0.07）、腹泻（P = 0.04）、乏力（P = 0.008）的风险较低，而发生任何级别恶心（P < 0.01）和呕吐（P < 0.01）的风险较高。无论年龄如何，接受FOLFOXIRI/bev治疗的患者比接受双药方案/bev治疗的患者更常发生≥G3级化疗相关不良事件（P = 0.60）。与年龄≥50岁的患者相比，年龄<50岁的患者接受FOLFOXIRI/bev治疗时，中性粒细胞减少症（P = 0.04）和乏力（P = 0.01）的发生率较低。PFS、OS和ORR在不同年龄组之间无差异（PFS P = 0.81，OS P = 0.44，ORR P = 0.50），且未观察到年龄与初始化疗强化带来的获益之间存在相互作用（PFS P = 0.72，OS P = 0.54，ORR P = 0.65）。对296例患者进行了基因组特征分析，结果显示EO-mCRC中FBXW7和POLE突变富集。
初始FOLFOXIRI/bev方案在EO-mCRC中显示出良好的疗效/安全性平衡。
Clinicaltrials.gov标识符NCT00719797、NCT0233 - 9116。
