Second-line chemotherapy after early disease progression during first-line chemotherapy containing bevacizumab for patients with metastatic colorectal cancer

BMC Cancer. 2021 Oct 29;21(1):1159. doi: 10.1186/s12885-021-08890-6.

Abstract

Background: The ML18174 study, which showed benefits of bevacizumab (BEV) continuation beyond progression (BBP) for metastatic colorectal cancer (mCRC), excluded patients with first-line progression-free survival (PFS) shorter than 3 months. The present study was conducted to evaluate the efficacy of second-line chemotherapy after early disease progression during first-line chemotherapy containing bevacizumab.

Methods: The subjects of this study were mCRC patients who experienced disease progression < 100 days from commencement of first-line chemotherapy containing BEV initiated between Apr 2007 and Dec 2016. Second-line chemotherapy regimens were classified into two groups with and without BEV/other anti-angiogenic agents (BBP and non-BBP) and efficacy and safety were compared using univariate and multivariate analysis.

Results: Sixty-one patients were identified as subjects of this study. Baseline characteristics were numerically different between BBP (n = 37) and non-BBP (n = 25) groups, such as performance status (0-1/> 2/unknown: 89/8/3 and 56/40/4%), RAS status (wild/mutant/unknown: 32/54/16 and 76/16/8%). Response rate was 8.6% in BBP group and 9.1% in non-BBP group (p = 1.00). Median PFS was 3.9 months in BBP group and 2.8 months in non-BBP group (HR [95%CI]: 0.79 [0.46-1.34], p = 0.373, adjusted HR: 0.87 [0.41-1.82], p = 0.707). Median overall survival was 8.5 months in BBP group and 5.4 months in non-BBP group (HR 0.66 [0.38-1.12], p = 0.125, adjusted HR 0.53 [0.27-1.07], p = 0.078).

Conclusion: In mCRC patients who experienced early progression in first-line chemotherapy, second-line chemotherapy showed poor clinical outcomes regardless use of anti-angiogenic agents.

Keywords: Bevacizumab continuation beyond progression; Early disease progression; Metastatic colorectal cancer; Second-line chemotherapy.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / therapeutic use*
  • Camptothecin / analogs & derivatives
  • Camptothecin / therapeutic use
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Drug Administration Schedule
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Irinotecan / therapeutic use
  • Japan
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin / therapeutic use
  • Progression-Free Survival
  • Pyrimidines / therapeutic use
  • Retrospective Studies
  • Time Factors

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Immunological
  • Organoplatinum Compounds
  • Pyrimidines
  • Oxaliplatin
  • Bevacizumab
  • Irinotecan
  • pyrimidine
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • FOLFOXIRI protocol
  • Folfox protocol