Therapeutic Advances in Medical Oncology (Dec 2022)

Predictive value of vascular endothelial growth factor polymorphisms for maintenance bevacizumab efficacy in metastatic colorectal cancer: an ancillary study of the PRODIGE 9 phase III trial

  • Bernadette de Rauglaudre,
  • Camille Sibertin-Blanc,
  • Aurélie Fabre,
  • Karine Le Malicot,
  • Jaafar Bennouna,
  • François Ghiringhelli,
  • Julien Taïeb,
  • Valérie Boige,
  • Olivier Bouché,
  • Thierry Chatellier,
  • Roger Faroux,
  • Eric François,
  • Stéphane Jacquot,
  • Dominique Genet,
  • Claire Mulot,
  • Sylviane Olschwang,
  • Jean-François Seitz,
  • Thomas Aparicio,
  • Laetitia Dahan

DOI
https://doi.org/10.1177/17588359221141307
Journal volume & issue
Vol. 14

Abstract

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Background: Several studies have reported the impact of single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor ( VEGF ) pathway genes on the efficacy of bevacizumab in metastatic colorectal cancer (mCRC), but results are still inconsistent. The PRODIGE 9 phase III study compared bevacizumab maintenance versus observation alone after induction chemotherapy with FOLFIRI plus bevacizumab. Objective: We evaluated the impact of SNPs of VEGF-A , VEGF receptors ( VEGFR-1, VEGFR-2 ), and hypoxia inducible factor-1α ( HIF-1α ) on tumor control duration (TCD), overall survival (OS), progression-free survival (PFS), and duration of first chemotherapy free-intervals (CFI). Patients and methods: We included 314/491 patients from PRODIGE 9 with a DNA blood sample available. Nine SNPs were genotyped on germline DNA using real-time Polymerase Chain Reaction TaqMan TM (Thermo Fisher Scientific, Waltham, MA , USA 02451). Results: In the bevacizumab arm, patients with the VEGFR-1 rs9582036 CC genotype ( n = 14) had significantly longer TCD [22.4 months (95% confidence interval (CI): 14.75-not reached)] than patients with the AA or CA genotype [14.4 months (95% CI: 11.7–17.1)] ( p = 0.036), whereas there was no significant difference in the observation arm. In the bevacizumab arm, no significant difference was found between the CC, and AA or CA genotype for OS [28.2 (95% CI: 18.1–42.8) versus 22.5 (95% CI: 18.6–24.6) months, p = 0.5], PFS [9.4 (95% CI: 7.2–11.3) versus 9.2 (95% CI: 8.71–10.1)], and duration of the first CFI [4.6 (95% CI: 1.6–13.3) versus 4.14 (95% CI: 0.5–29.0) months, p = 0.3]. Conclusion: Among mCRC patients treated with bevacizumab maintenance, those with the VEGFR-1 rs9582036 CC genotype experienced longer TCD. The presence of this genotype may thus predict a benefit of bevacizumab maintenance in mCRC.