Alternating modified CAPOX/CAPIRI plus bevacizumab in untreated unresectable metastatic colorectal cancer: a phase 2 trial

Signal Transduct Target Ther. 2024 Dec 11;9(1):346. doi: 10.1038/s41392-024-02048-z.

Abstract

Previous studies showed encouraging efficacy of alternating FOLFOX/FOLFIRI for metastatic colorectal cancer (mCRC). This phase 2 trial (NCT04324476) aimed to evaluate efficacy and safety of alternating modified CAPOX (capecitabine and oxaliplatin)/modified CAPIRI (capecitabine and irinotecan) plus bevacizumab (anti-VEGF-A antibody) in untreated unresectable mCRC. Induction treatment included capecitabine 1000 mg/m2 bid D2-8 and D16-22, oxaliplatin 85 mg/m2 D1, irinotecan 150 mg/m2 D15, and bevacizumab 5 mg/kg D1 and 15 for 28-day cycles (up to six cycles). Capecitabine 1000 mg/m2 bid D2-15 and bevacizumab 7.5 mg/kg D1 for 21-day cycles were used as maintenance treatment. 52 patients were included. Median follow-up was 25.0 months. Median progression-free survival (PFS; the primary endpoint) was 11.0 months (95% CI 9.0-12.4). Subgroup analyses showed patients with neutrophil-to-lymphocyte ratio<5 or RAS wild-type disease had longer PFS (both P < 0.05). Objective response and disease control were obtained in 38 (73%; 95% CI 59%-84%) and 49 (94%; 95% CI 84%-99%), respectively. Mean depth of response, conversion and no evidence of disease rates were 46.0% ± 26.3%, 23% and 19%, respectively. Median overall survival was 28.1 months (18.4-34.0). Grade 3-4 treatment-related adverse events (TRAE) occurred in 17 (33%) patients. No treatment-related death was reported. The most common grade 3-4 TRAE were hypertension (13 [25%]), neutrophil count decreased (three [6%]), and hand-foot syndrome (two [4%]). In addition, grade 3-4 TRAE of diarrhea reported in one [2%] patient and no grade 3-4 peripheral neuropathy occurred. Thus, alternating modified CAPOX/CAPIRI plus bevacizumab had promising efficacy and acceptable safety. The regimen may be a novel option for untreated unresectable mCRC.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Bevacizumab* / administration & dosage
  • Capecitabine* / administration & dosage
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / pathology
  • Female
  • Humans
  • Irinotecan* / administration & dosage
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Oxaliplatin / administration & dosage
  • Oxaliplatin / adverse effects

Substances

  • Bevacizumab
  • Capecitabine
  • Irinotecan
  • Oxaliplatin