A phase II study of erlotinib (E) and bevacizumab (B) in chemo naive patients (pts) with locally advanced or metastatic non small cell lung cancer (NSCLC): Predictive value of molecular imaging

Boogaart, V. van den; Langen, Adrianus De; Groen, Harry J.M.; Marcus, J. Tim; Kappert, Peter; Backes, Walter H.; Brans, Boudewijn; Hoekstra, O. S.; Dingemans, Anne‐Marie C.; Smit, Egbert F.

doi:10.1200/jco.2008.26.15_suppl.8055

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“…Reports in the literature of the predictive value of CD31 with different antiangiogenic agents have been inconsistent [31, 51, 52]. Finally, in contrast to other studies involving agents that target VEGFR or EGFR pathways [53–57], we did not find a relationship between decrease in SUV and clinical outcome. Given the small sample size and the heterogeneity of our patient population, these results may have limited power to detect subtle associations even if they exist.…”

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confidence: 99%

Phase I Combination of Sorafenib and Erlotinib Therapy in Solid Tumors: Safety, Pharmacokinetic, and Pharmacodynamic Evaluation from an Expansion Cohort

Quintela‐Fandino

Tourneau

Durán

et al. 2010

Molecular Cancer Therapeutics

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The aims of this study were to further define the safety of sorafenib and erlotinib, given at their full approved monotherapy doses, and to correlate pharmacokinetic and pharmacodynamic markers with clinical outcome. In addition, a novel pharmacodynamic marker based on the real-time measurement of RAF signal transduction capacity (STC) is described. Sorafenib was administered alone for a 1-week run-in period, and then both drugs were given together continuously. RAF STC was assessed in peripheral blood monocytes prior to erlotinib initiation. Epidermal growth factor receptor (EGFR) expression and K-RAS mutations were measured in archival tumor samples. Changes in pERK and CD31 were determined in fresh tumor biopsies obtained pretreatment, prior to erlotinib dosing, and during the administration of both drugs. In addition, positron emission tomography-computed tomography scans and pharmacokinetic assessments were done. Eleven patients received a total of 57 cycles (median, 5; range, 1-10). Only four patients received full doses of both drugs for the entire study course, with elevation of liver enzymes being the main reason for dose reductions and delays. Among 10 patients evaluable for response, 8 experienced tumor stabilization of ≥4 cycles. Pharmacokinetic analysis revealed no significant interaction of erlotinib with sorafenib. Sorafenib-induced decrease in RAF-STC showed statistically significant correlation with time-to-progression in seven patients. Other pharmacodynamic markers did not correlate with clinical outcome. This drug combination resulted in promising clinical activity in solid tumor patients although significant toxicity warrants close monitoring. RAF-STC deserves further study as a predictive marker for sorafenib. Mol Cancer Ther; 9(3); 751-60. ©2010 AACR.

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