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Clinical Trial
. 2014 Jun;3(3):572-9.
doi: 10.1002/cam4.208. Epub 2014 Feb 12.

Phase II trial of sorafenib and erlotinib in advanced pancreatic cancer

Dana B Cardin  1 , Laura Goff, Chung-I Li, Yu Shyr, Charles Winkler, Russell DeVore, Larry Schlabach, Melanie Holloway, Pam McClanahan, Krista Meyer, Julia Grigorieva, Jordan Berlin, Emily Chan
Affiliations
Clinical Trial

Phase II trial of sorafenib and erlotinib in advanced pancreatic cancer

Dana B Cardin et al. Cancer Med. 2014 Jun.

Abstract

This trial was designed to assess efficacy and safety of erlotinib with sorafenib in the treatment of patients with advanced pancreatic adenocarcinoma. An exploratory correlative study analyzing pretreatment serum samples using a multivariate protein mass spectrometry-based test (VeriStrat®), previously shown to correlate with outcomes in lung cancer patients treated with erlotinib, was performed. Patients received sorafenib 400 mg daily along with erlotinib 150 mg daily with a primary endpoint of 8-week progression free survival (PFS) rate. Pretreatment serum sample analysis by VeriStrat was done blinded to clinical and outcome data; the endpoints were PFS and overall survival (OS). Difference between groups (by VeriStrat classification) was assessed using log-rank P values; hazard ratios (HR) were obtained from Cox proportional hazards model. Thirty-six patients received study drug and were included in the survival analysis. Eight-week PFS rate of 46% (95% confidence interval (CI): 0.32-0.67) did not meet the primary endpoint of a rate ≥70%. Thirty-two patients were included in the correlative analysis, and VeriStrat "Good" patients had superior PFS (HR = 0.18, 95% CI: 0.06-0.57; P = 0.001) and OS (HR = 0.31 95% CI: 0.13-0.77, P = 0.008) compared to VeriStrat "Poor" patients. Grade 3 toxicities of this regimen included fever, anemia, diarrhea, dehydration, rash, and altered liver function. This study did not meet the primary endpoint, and this combination will not be further pursued. In this small retrospective analysis, the proteomic classification was significantly associated with clinical outcomes and is being further evaluated in ongoing studies.

Keywords: Erlotinib; pancreatic cancer; sorafenib; targeted therapy.

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Figures

Figure 1
Figure 1
The 8-week progression-free survival rate is 46% (95% CI: 0.32–0.67). In order to achieve statistical significance, an 8-week progression-free survival rate ≥70% was needed.
Figure 2
Figure 2
Kaplan–Meier plots of PFS (A) and OS (B) grouped by VeriStrat Classification
See this image and copyright information in PMC

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