FOLFOXIRI and bevacizumab in patients with early-onset metastatic colorectal cancer. A pooled analysis of TRIBE and TRIBE2 studies

Eur J Cancer. 2022 May:167:23-31. doi: 10.1016/j.ejca.2022.02.031. Epub 2022 Mar 30.

Abstract

Background: 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.

Materials and methods: 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.

Results: 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 (Pinteraction = 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 Pinteraction = 0.72, OS Pinteraction = 0.54, ORR Pinteraction = 0.65). Genomic profiling was assessed in 296 patients, showing an enrichment of FBXW7 and POLE mutations in EO-mCRC.

Conclusions: Upfront FOLFOXIRI/bev shows a favourable efficacy/safety balance in EO-mCRC.

Trial registration: Clinicaltrials.gov Identifiers NCT00719797, NCT0233-9116.

Trial registration: ClinicalTrials.gov NCT00719797 NCT00000233.

Keywords: Early onset; Efficacy; FOLFOXIRI plus Bevacizumab; Genomic alterations; Metastatic colorectal cancer; Safety.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Asthenia / chemically induced
  • Bevacizumab / adverse effects
  • Camptothecin / analogs & derivatives
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Female
  • Fluorouracil / adverse effects
  • Humans
  • Leucovorin / adverse effects
  • Middle Aged
  • Neutropenia* / chemically induced
  • Organoplatinum Compounds

Substances

  • Organoplatinum Compounds
  • Bevacizumab
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • FOLFOXIRI protocol

Associated data

  • ClinicalTrials.gov/NCT00719797
  • ClinicalTrials.gov/NCT00000233