Phase I study to assess the safety and tolerability of olaparib in combination with bevacizumab in patients with advanced solid tumours

Br J Cancer. 2012 Jan 31;106(3):468-74. doi: 10.1038/bjc.2011.555. Epub 2012 Jan 5.


Background: Olaparib (AZD2281) is a potent oral poly(ADP-ribose) polymerase inhibitor with anti-tumour activity and acceptable toxicity as monotherapy in patients with BRCA-deficient cancers. The vascular endothelial growth factor receptor inhibitor bevacizumab has been incorporated into standard of care with chemotherapy in various tumours. This phase I study established the safety, tolerability and clinical pharmacokinetics of olaparib alone and in combination with bevacizumab.

Methods: Patients with advanced solid tumours received increasing doses of continuous oral olaparib (100, 200 and 400 mg b.i.d. capsule formulation) in combination with bevacizumab (10 mg kg(-1) intravenous q2w).

Results: In all, 12 patients enrolled and received treatment. The most common adverse events (AEs) related to olaparib were grade 1/2 nausea and fatigue. No haematological parameters were reported as AEs. No serious AEs related to olaparib or dose-limiting toxicities (DLTs) were reported. Three patients discontinued due to AEs, two patients discontinued both olaparib and bevacizumab and one patient discontinued olaparib. Five patients received combination treatment for over 6 months. There was no evidence that bevacizumab affected olaparib.

Conclusion: The combination of olaparib 400 mg b.i.d. with bevacizumab 10 mg kg(-1) q2w was generally well tolerated with no DLTs. This combination could be considered for future clinical investigation.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacokinetics
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / pharmacokinetics*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Phthalazines / administration & dosage
  • Phthalazines / adverse effects
  • Phthalazines / pharmacokinetics*
  • Piperazines / administration & dosage
  • Piperazines / adverse effects
  • Piperazines / pharmacokinetics*
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
  • Treatment Outcome
  • Young Adult


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Phthalazines
  • Piperazines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Bevacizumab
  • Receptors, Vascular Endothelial Growth Factor
  • olaparib