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

• Published in: Journal of thoracic oncology 2013-03, Vol.8 (3), p.369-372
• Main Authors: Ramalingam, Suresh S., Owonikoko, Taofeek K., Behera, Madhusmita, Subramanian, Janakiraman, Saba, Nabil F., Kono, Scott A., Gal, Anthony A., Sica, Gabriel, Harvey, R. Donald, Chen, Zhengjia, Klass, Carmen M., Shin, Dong M., Fu, Haian, Sun, Shi-yong R., Govindan, Ramaswamy, Khuri, Fadlo R.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - metabolism; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Docetaxel; Everolimus; Female; Follow-Up Studies; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Middle Aged; Neoplasm Staging; Non–small-cell lung cancer; Prognosis; Sirolimus - administration & dosage; Sirolimus - analogs & derivatives; Survival Rate; Taxoids - administration & dosage; TOR Serine-Threonine Kinases - metabolism
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1097/JTO.0b013e318282709c

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.