Efficacy of everolimus (RAD001) in patients with advanced NSCLC previously treated with chemotherapy alone or with chemotherapy and EGFR inhibitors

被引:136
作者
Soria, J. -C. [2 ]
Shepherd, F. A. [3 ]
Douillard, J. -Y. [4 ]
Wolf, J. [5 ]
Giaccone, G. [6 ]
Crino, L. [7 ]
Cappuzzo, F. [8 ]
Sharma, S. [9 ,10 ]
Gross, S. H. [11 ]
Dimitrijevic, S. [11 ]
Di Scala, L. [11 ]
Gardner, H.
Nogova, L. [5 ]
Papadimitrakopoulou, V. [1 ]
机构
[1] Univ Texas Houston, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA
[2] Inst Gustave Roussy, Lung Canc Unit, Villejuif, France
[3] Princess Margaret Hosp, Dept Med Oncol & Hematol, Toronto, ON M4X 1K9, Canada
[4] Rene Gauducheau Canc Ctr, Med Oncol Branch, St Herblain, France
[5] Univ Hosp Cologne, Ctr Integrated Oncol, Dept Internal Med 1, Cologne, Germany
[6] Vrije Univ Amsterdam Med Ctr, Dept Med Oncol, Amsterdam, Netherlands
[7] Silvestrini Hosp, Dept Oncol, Perugia, Italy
[8] Humanitas Clin Inst, Dept Med Oncol, Milan, Italy
[9] Nevada Canc Inst, Sect Phase 1, Las Vegas, NV USA
[10] Nevada Canc Inst, Sect Gastrointestinal Oncol, Las Vegas, NV USA
[11] Novartis Oncol, Oncol Clin Dev, Basel, Switzerland
关键词
everolimus; mTOR; non-small-cell lung cancer; NSCLC; RAD001; CELL-LUNG-CANCER; AKT OVEREXPRESSION; INDUCED APOPTOSIS; THERAPY; RAPAMYCIN; PROTEIN; TUMORS; MTOR; ACTIVATION; EXPRESSION;
D O I
10.1093/annonc/mdp060
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Treatment options are scarce in pretreated advanced non-small-cell lung cancer (NSCLC) patients. RAD001, an oral inhibitor of the mammalian target of rapamycin (mTOR), has shown phase I efficacy in NSCLC. Methods: Stage IIIb or IV NSCLC patients, with two or fewer prior chemotherapy regimens, one platinum based (stratum 1) or both chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitors (stratum 2), received RAD001 10 mg/day until progression or unacceptable toxicity. Primary objective was overall response rate (ORR). Analyses of markers associated with the mTOR pathway were carried out on archival tumor from a subgroup using immunohistochemistry (IHC) and direct mutation sequencing. Results: Eighty-five patients were enrolled, 42 in stratum 1 and 43 in stratum. ORR was 4.7% (7.1% stratum 1; 2.3% stratum 2). Overall disease control rate was 47.1%. Median progression-free survivals (PFSs) were 2.6 (stratum 1) and 2.7 months (stratum 2). Common >= grade 3 events were fatigue, dyspnea, stomatitis, anemia, and thrombocytopenia. Pneumonitis, probably or possibly related, mainly grade 1/2, occurred in 25%. Cox regression analysis of IHC scores found that only phospho AKT (pAKT) was a significant independent predictor of worse PFS. Conclusions: RAD001 10 mg/day was well tolerated, showing modest clinical activity in pretreated NSCLC. Evaluation of RAD001 plus standard therapy for metastatic NSCLC continues.
引用
收藏
页码:1674 / 1681
页数:8
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