Randomised phase III study of bevacizumab + chemotherapy beyond progression in bevacizumab-treated patients with metastatic colorectal cancer: TML study KRAS subgroup findings

  • E. V
  • J. M
  • O. B
 et al. 
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Introduction: Bevacizumab in combination with fluoropyrimidine-based chemotherapy is a standard treatment for patients with metastatic colorectal cancer (mCRC) in the first-line and bevacizumab-naive second-line settings. This randomised study evaluated the benefit of continuing bevacizumab with standard chemotherapy as second-line treatment for patients with mCRC who progressed after receiving a standard bevacizumab-containing regimen in the first-line setting. The study included a broad biomarker collection as an exploratory objective. We present here analysis of outcomes according to tumour KRAS status. Methods: Patients with unresectable, histologically confirmed mCRC who progressed within 3 months after discontinuation of first-line bevacizumab + chemotherapy were randomised to second-line fluoropyrimidine-based chemotherapy (plus or minus) bevacizumab (2.5 mg/kg/wk equivalent). The choice of oxaliplatin- or irinotecan-based second-line chemotherapy was based on the regimen used in the first-line setting (crossover) and was included in the stratification variables. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), response rate and safety. Subgroup analysis according to KRAS status was performed for both OS and PFS; no adjustment was made for multiplicity. Results: Conclusive tumour KRAS mutation data were available for 616 of the 820 patients (75{%}). Baseline characteristics were similar in the biomarker and randomised populations. Overall, 300 (49{%}) patients had mutant-type (MT) KRAS tumours and 316 (51{%}) had wild-type (WT) KRAS tumours. Median OS in the KRAS WT group was 15.4 months for bevacizumab + chemotherapy vs 11.1 months for chemotherapy alone (p = 0.0052; HR = 0.69) and 10.4 months for bevacizumab + chemotherapy vs 10.0 months for chemotherapy alone in the KRAS MT group (p = 0.4969; HR = 0.91). Median PFS in the KRAS WT group was 6.4 months for bevacizumab + chemotherapy vs 4.5 months for chemotherapy alone (p {

Author-supplied keywords

  • arm
  • bevacizumab
  • biological marker
  • chemotherapy
  • digestive system cancer
  • fluoropyrimidine
  • human
  • irinotecan
  • metastatic colorectal cancer
  • mutant
  • mutation
  • neoplasm
  • overall survival
  • oxaliplatin
  • patient
  • population
  • progression free survival
  • safety
  • stratification
  • wild type

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  • Van Cutsem E.

  • Maria Vieitez J.

  • Bouche O.

  • Osterlund P.

  • Bennouna J.

  • Andre T.

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