Phase II Study of Docetaxel in Combination with Everolimus for Second- or Third-Line Therapy of Advanced Non-Small-Cell Lung Cancer

• Type of Material: Article
• Authors: Suresh S Ramalingam, Emory University; Taofeek K Owonikoko, Emory University; Madhusmita Behera, Emory University; Janakiraman Subramanian, Washington University School of Medicine; Nabil F Saba, Emory University; Scott A. Kono, Emory University; Anthony A Gal, Emory University; Gabriel Sica, Emory University; R Donald Harvey, Emory University; Zhengjia Chen, Emory University; Carmen M. Klass, Northwest Georgia Oncology Centers; Dong M Shin, Emory University; Haian Fu, Emory University; Shi-Yong Sun, Emory University; Ramaswamy Govindan, Washington University School of Medicine; Fadlo Khuri, Emory University
• Language: English
• Date: 2013-03
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 by the International Association for the Study of Lung Cancer
• Final Published Version (URL): http://journals.lww.com/jto/pages/articleviewer.aspx?year=2013&issue=03000&article=00018&type=abstract
• Title of Journal or Parent Work: Journal of Thoracic Oncology
• ISSN: 1556-0864
• Volume: 8
• Issue: 3
• Start Page: 369
• End Page: 372
• Grant/Funding Information: This study was supported in part by National Institutes of Health 1PO1 CA116676 and a research grant from Novartis Pharmaceuticals.
• Keywords: Non–small-cell lung cancer; Docetaxel; Everolimus
• Research Categories: Health Sciences, Oncology; Health Sciences, Pathology

Abstract

We conducted a phase II study of docetaxel in combination with everolimus, a mammalian target of rapamycin (mTOR) inhibitor, for salvage therapy of advanced non–small-cell lung cancer (NSCLC) based on promising preclinical and early-phase clinical data. Patients with advanced-stage NSCLC treated with one or two previous systemic therapy regimens were given docetaxel (60 mg/m2) and everolimus (5 mg orally once daily on days 1–19) every 3 weeks. Archived tumor specimens were evaluated for markers of mTOR pathway activation (total and phosphorylated mTOR, Akt, S6, eIF4e, and 4EBP1). Twenty-eight patients were enrolled (median age: 62 years; male: 13; Caucasians: 19; adenocarcinoma: 20; performance status 0, 3; performance status 1, 23; 1 previous regimen, 16). A median of 3.5 cycles of therapy was administered. Two patients experienced partial response and 15 had stable disease (clinical benefit rate, 70%). The 6-month progression-free survival rate was 5%, and the median overall survival was 9.6 months. Low pAkt expression correlated with clinical benefit rate (p = 0.01) but not with progression-free survival or overall survival. The combination of everolimus and docetaxel was tolerated well, but the efficacy was relatively modest in an unselected population of patients with NSCLC.