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

http://www.ncbi.nlm.nih.gov/pubmed/23407561

J Thorac Oncol. 2013 Mar;8(3):369-72. doi: 10.1097/JTO.0b013e318282709c.

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

Ramalingam SS, Owonikoko TK, Behera M, Subramanian J, Saba NF, Kono SA, Gal AA, Sica G, Harvey RD, Chen Z, Klass CM, Shin DM, Fu H, Sun SY,Govindan R, Khuri FR.

Source

*Department of Hematology and Medical Oncology, Emory University, Winship Cancer Institute, Atlanta, Georgia; †Division of Oncology, Washington University School of Medicine, St. Louis, Missouri; Departments of ‡Pathology and §Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia; and ¶Northwest Georgia Oncology Centers, Atlanta, Georgia.

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 NSCLCtreated with one or two previous systemic therapy regimens were given docetaxel (60 mg/m) 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.