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.
Copyright © 2022 Elsevier Ltd. All rights reserved.
About The Expert
Carlotta Antoniotti
Marco M Germani
Daniele Rossini
Sara Lonardi
Filippo Pietrantonio
Daniele Santini
Federica Marmorino
Giacomo Allegrini
Francesca Daniel
Alessandra Raimondi
Beatrice Borelli
Alberto Zaniboni
Veronica Conca
Jim Abraham
David Spetzler
Evaristo Maiello
Alessandra Boccaccino
Alessandro Passardi
Mirella Giordano
Emiliano Tamburini
Michael W Korn
Gianluca Masi
Chiara Cremolini
References
PubMed