Feasibility of adding everolimus to carboplatin and paclitaxel, with or without bevacizumab, for treatment-naive, advanced non-small cell lung cancer.

Feasibility of adding everolimus to carboplatin and paclitaxel, with or without bevacizumab, for treatment-naive, advanced non-small cell lung cancer.

Invest New Drugs. 2013 Apr 12;

Authors: Eberhardt WE, Mitchell P, Schiller JH, Brown MP, Thomas M, Mills G, Jehl V, Urva SR, De Leo JJ, Gogov S, Papadimitrakopoulou V

Abstract
Introduction One standard of care for advanced non-small cell lung cancer (NSCLC) is paclitaxel plus carboplatin?�?bevacizumab. This two-step phase I study evaluated the feasibility of adding everolimus to paclitaxel plus carboplatin?�?bevacizumab for advanced NSCLC. Methods Adults with advanced NSCLC naive to systemic therapy were enrolled. A Bayesian dose-escalation model was used to identify feasible daily or weekly everolimus doses given with paclitaxel (200�mg/m(2) q21 days) and carboplatin (AUC 6�mg/mL/min q21 days) (step 1) and paclitaxel (200�mg/m(2) q21 days), carboplatin (AUC 6�mg/mL/min q21 days), and bevacizumab (15�mg/kg q21 days) (step 2). Primary endpoint was end-of-cycle 1 dose-limiting toxicity (DLT) rate. Secondary endpoints included safety; relative dose intensities of paclitaxel, carboplatin, and bevacizumab; pharmacokinetics; and tumor response. Results Fifty-two patients were enrolled and received everolimus 5�mg/day plus carboplatin and paclitaxel (step 1 daily; n?=?13); everolimus 30�mg/week plus carboplatin and paclitaxel (step 1 weekly; n?=?13); everolimus 5�mg/day plus carboplatin, paclitaxel, and bevacizumab (step 2 daily; n?=?13); or everolimus 30�mg/week plus carboplatin, paclitaxel, and bevacizumab (step 2 weekly; n?=?13). End-of-cycle 1 DLT rate was 16.7�% (step 1 daily), 30.8�% (step 1 weekly), 30.0�% (step 2 daily), and 16.7�% (step 2 weekly). Cycle 1 DLTs were grade 3 neutropenia, anal abscess, diarrhea, and thrombocytopenia and grade 4 myalgia, cellulitis, neutropenia, febrile neutropenia, pulmonary embolism, and thrombocytopenia. The most common adverse events were neutropenia, fatigue, anemia, and thrombocytopenia. One patient (step 2 daily) experienced complete response, 10 patients partial response. Conclusions The feasible everolimus doses given with carboplatin and paclitaxel?�?bevacizumab were 5�mg/day and 30�mg/week. Neither schedule was very well tolerated in this unselected NSCLC population.

PMID: 23579358 [PubMed - as supplied by publisher]

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