| General information |
| Database: | DB00672 |
| Objective: | No standard of care exists for patients with metastatic pancreatic cancer following progression on firstline chemotherapy. Based on potential for additive or synergistic activity by concurrent inhibition of VEGF and EGFR, they conducted a phase II study evaluating the combination of bevacizumab plus erlotinib in this patient population. |
| Authors: | Ko AH, et al |
| Title: | a phase II study of bevacizumab plus erlotinib for gemcitabinerefractory metastatic pancreatic cancer. |
| Journal: | Cancer Chemother Pharmacol |
| Year: | 2010 |
| PMID: | 20130876 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | bevacizumab and erlotinib
|
| Target: | NA
|
| Cancer Type: | pancreatic cancer |
| Cancer Subtype: | advanced pancreatic adenocarcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | bevacizumab+ erlotinib |
| Study Type: | a phase II, single center, openlabel, singlearmstudy |
| Key Patients Feature: | patients were eligible for this study if they were 18 years ofage or older, had an ECOG performance status of 0 or 1, and had a conWrmed diagnosis of pancreatic adenocarcinoma with radiographic or biopsyproven evidence ofextrapancreatic metastases (stage IVb). Those with locallyadvanced unresectable disease only were not eligible.Extrapancreatic metastases did not have to be measurableby formal RECIST criteria. Patients must have received atleast one, but no more than three, prior systemic therapiesfor advanced disease (locally advanced or metastatic), atleast one of which was gemcitabinebased. Chemotherapygiven in the adjuvant setting either alone or concurrentlywith radiation did not count as prior therapy as long as progressive disease occurred >6 months following completionof treatment. patients were allowed to have received eitheran antiVEGF or an antiEGFR agent as part of their priortherapy, but not both.Adequate hematologic, renal, and hepatic function wasrequired as deWned by the following: absolute neutrophilcount 1, 500/ l, platelet count 100, 000/ l, hemoglobin 9 g/dl, an international normalized ratio . 1.5 (exceptfor participants receiving fulldose warfarin at the time ofstudy entry), creatinine level . 2.0 mg/dl, bilirubinlevel . 2.0 mg/dl, and transaminases . 2.5x ULN (.5xULN in patients with liver metastases). Any major surgicalprocedure had to be completed more than 28 days from thetime of study entry. Female patients of childbearing potential must have had a negative urine pregnancy test beforestudy entry. |
| Biomarker: | circulating endothelial cells (CD45()/CD34(+)/CD31(+)) |
| Biomark Analysis: | Baseline concentration of circulating endothelial cells (CD45()/CD34(+)/CD31(+)) was inversely associated with overall survival. |
| Control Group Info: | single arm |
| Treatment Info: | Treatment consisted of bevacizumab 15 mg/kg every 21 days plus erlotinib 150 mg daily. |
| Primary End Point: | overall survival rate at 6 months |
| Secondary End Point: | time to tumor progression (TTP), objective response rate by RECIST criteria in patients with measurable disease at baseline, and CA199 biomarker response |
| Patients Number: | 36 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | One patient demonstrated partial response and seven others stable disease for >2 cycles. CA199 decline more than and equal to 25% was observed in 4/26 patients with baseline levels >2x ULN. |
| Disease Control Rate: | NA |
| Median Time to Progression: | 40 (35-41) days |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 102 (74-117) days |
| Adverse Event(agent arm): | Common toxicities included rash (72%), diarrhea (25%), venous thromboembolic events (15%), and hypertension (11%). |
| Conclusions: | The combination of bevacizumab and erlotinib is safe but relatively ineffective in patients with gemcitabinerefractory metastatic pancreatic cancer. Future studies should focus on refining subsets of patients in this challenging population likely to benefit from treatment beyond firstline. |