Switching from FOLFIRI plus cetuximab to FOLFIRI plus bevacizumab based on early tumor shrinkage in RAS wild-type metastatic colorectal cancer: A phase II trial (HYBRID)

Cancer Med. 2024 Apr;13(7):e7107. doi: 10.1002/cam4.7107.


Background: Long-term anti-EGFR antibody treatment increases the risk of severe dermatologic toxicities. This single-arm, phase II trial aimed to investigate the strategy of switching from cetuximab to bevacizumab in combination with FOLFIRI based on early tumor shrinkage (ETS) in patients with RAS wild-type metastatic colorectal cancer (mCRC).

Methods: Radiologic assessment was performed to evaluate ETS, defined as ≥20% reduction in the sum of the largest diameters of target lesions 8 weeks after the introduction of FOLFIRI plus cetuximab. ETS-negative patients switched to FOLFIRI plus bevacizumab, whereas ETS-positive patients continued FOLFIRI plus cetuximab for eight more weeks, with a switch to FOLFIRI plus bevacizumab thereafter. The primary endpoint was progression-free survival.

Results: This trial was prematurely terminated due to poor accrual after a total enrollment of 30 patients. In 29 eligible patients, 7 were ETS-negative and 22 were ETS-positive. Two ETS-negative patients and 17 ETS-positive patients switched to FOLFIRI plus bevacizumab 8 weeks and 16 weeks after initial FOLFIRI plus cetuximab, respectively. Median progression-free and overall survival durations were 13.4 and 34.7 months, respectively. Six (20%) patients experienced grade ≥3 paronychia, which improved to grade ≤2 by 18 weeks. Grade ≥3 acneiform rash, dry skin, and pruritus were not observed in any patients.

Conclusions: Our novel treatment strategy delivered acceptable survival outcomes and reduced severe dermatologic toxicities.

Keywords: bevacizumab; cetuximab; early tumor shrinkage; metastatic colorectal cancer.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bevacizumab / adverse effects
  • Camptothecin / adverse effects
  • Cetuximab / adverse effects
  • Colonic Neoplasms* / etiology
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Fluorouracil / adverse effects
  • Humans
  • Leucovorin / adverse effects
  • Rectal Neoplasms* / etiology


  • Bevacizumab
  • Cetuximab
  • Camptothecin
  • Fluorouracil
  • Leucovorin