A phase II study of bevacizumab plus erlotinib for gemcitabine-refractory metastatic pancreatic cancer

Cancer Chemother Pharmacol. 2010 Nov;66(6):1051-7. doi: 10.1007/s00280-010-1257-5. Epub 2010 Feb 4.

Abstract

Purpose: No standard of care exists for patients with metastatic pancreatic cancer following progression on first-line chemotherapy. Based on potential for additive or synergistic activity by concurrent inhibition of VEGF and EGFR, we conducted a phase II study evaluating the combination of bevacizumab plus erlotinib in this patient population.

Methods: Patients with metastatic pancreatic adenocarcinoma, ECOG performance status 0-1, and previous exposure to 1-3 systemic therapies (at least one gemcitabine-based) were eligible. Treatment consisted of bevacizumab 15 mg/kg every 21 days plus erlotinib 150 mg daily.

Results: Thirty-six patients were enrolled, including eight who had previously received VEGF-targeted therapy and nine prior erlotinib. Median number of treatment cycles was 2 (range, 1-7). Common toxicities included rash (72%), diarrhea (25%), venous thromboembolic events (15%), and hypertension (11%). One patient demonstrated partial response and seven others stable disease for >2 cycles. CA19-9 decline ≥25% was observed in 4/26 patients with baseline levels >2x ULN. Estimated median time to progression was 40 days (95% CI, 35-41 days) and median survival 102 days (95% CI, 74-117 days), with a 6-month survival rate of 22%. Baseline concentration of circulating endothelial cells (CD45(-)/CD34(+)/CD31(+)) was inversely associated with overall survival.

Conclusions: The combination of bevacizumab and erlotinib is safe but relatively ineffective in patients with gemcitabine-refractory metastatic pancreatic cancer. Future studies should focus on refining subsets of patients in this challenging population likely to benefit from treatment beyond first-line.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Antimetabolites, Antineoplastic* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Disease Progression
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm*
  • Erlotinib Hydrochloride
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / ethnology
  • Pancreatic Neoplasms / pathology*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antimetabolites, Antineoplastic
  • Protein Kinase Inhibitors
  • Quinazolines
  • Deoxycytidine
  • Bevacizumab
  • gemcitabine
  • Erlotinib Hydrochloride