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

• Published in: Cancer chemotherapy and pharmacology 2010-11, Vol.66 (6), p.1051-1057
• Main Authors: Ko, Andrew H, Venook, Alan P, Bergsland, Emily K, Kelley, R. Kate, Korn, W. Michael, Dito, Elizabeth, Schillinger, Brian, Scott, Janet, Hwang, Jimmy, Tempero, Margaret A
• Format: Article
• Language: English
• Subjects: 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 agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Biological and medical sciences; Cancer Research; Circulating endothelial cells; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Disease Progression; Drug Administration Schedule; Drug Resistance, Neoplasm; Erlotinib; Erlotinib Hydrochloride; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Kaplan-Meier Estimate; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original Article; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - ethnology; Pancreatic Neoplasms - pathology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Phase II; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Quinazolines - administration & dosage; Quinazolines - adverse effects; Refractory; Treatment Outcome; Tumors
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-010-1257-5

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.