Phase I study of polyphenon E (P) in addition to erlotinib (E) in advanced non-small cell lung cancer (NSCLC).

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e18050 Background: E is an oral tyrosine kinase inhibitor (TKI) that targets the epidermal growth factor receptor (EGFR). Polyphenon E is a green tea extract containing mainly epigallocatechin gallate (EGCG) which inhibits c-met and vascular endothelial growth factor (VEGF) signaling. In vitro studies and in vivo tumor models have demonstrated synergism from EGCG when to added E . This phase I study evaluated safety and tolerability of P and E in patients (pts) with advanced NSCLC. Methods: Pts with stage IV NSCLC who had progressed after first or second line chemotherapy were included in the study. Pts were enrolled in cohorts of 3 with increasing dose of P (200mg, 400mg and 800mg PO once daily). E was given at 150mg/day continuously in 28 day cycles. End points were safety, tolerability and maximum tolerated dose (MTD) of P in combination with E. Results: Between April 2008 and Nov 2010 a total of 11 pts were enrolled. Two pts were not included in the final analysis as they discontinued therapy due to progression or worsening of performance status prior to completing the required minimum of 4 weeks of treatment. Median age was 64.6 years (range 57-75). All pts were male and all were current or former smokers. Seven patients had squamous cell histology and two had adenocarcinoma. There were no serious adverse events. Four pts developed acneiform rash (2 – grade 2 and 2 – grade 1). One patient developed herpes zoster deemed unrelated to treatment. One patient in the 400mg cohort developed grade 2 transaminitis which resolved after temporarily holding E and P. MTD of P in combination with E was not reached. Nine patients were assessed for tumor response, 6 patients had stable disease and 3 had progression of disease. The median progression-free survival for the entire group was 3 months. Conclusions: The combination of P and E was well-tolerated with no dose limiting toxicity observed at the maximum planned dose of P of 800mg. Preliminary efficacy data suggest a progression-free survival that is modestly better than that reported with E alone. This is the first reported trial evaluating the addition of P to E in NSCLC. Larger prospective studies are required to better define the role of this combination as second-line therapy in advanced NSCLC.

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