Everolimus and Erlotinib as Second- or Third-Line Therapy in Patients with Advanced Non-Small-Cell Lung Cancer

被引:30
作者
Papadimitrakopoulou, Vassiliki A. [1 ]
Soria, Jean-Charles [2 ,3 ]
Jappe, Annette [4 ,5 ]
Jehl, Valentine [4 ,5 ]
Klimovsky, Judith [4 ,5 ]
Johnson, Bruce E. [6 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA
[2] Inst Gustave Roussy, Villejuif, France
[3] Univ Paris 11, Villejuif, France
[4] Novartis Pharmaceut, Basel, Switzerland
[5] Novartis Pharmaceut, Florham Pk, NJ USA
[6] Dana Farber Canc Inst, Boston, MA 02115 USA
关键词
Dose-limiting toxicity; Erlotinib; Everolimus; Non-small-cell lung cancer; Phase I; RAPAMYCIN INHIBITOR EVEROLIMUS; CLINICAL-PRACTICE GUIDELINES; ADVANCED SOLID TUMORS; MAMMALIAN TARGET; EGFR INHIBITORS; FOLLOW-UP; GEFITINIB; TRIAL; CHEMOTHERAPY; STAGE;
D O I
10.1097/JTO.0b013e3182614835
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Introduction: The epidermal growth factor receptor inhibitor erlotinib is an approved treatment for chemotherapy-refractory advanced non-small-cell lung cancer (NSCLC). Because activated epidermal growth factor receptor signals through the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway, adding the oral mTOR inhibitor everolimus to erlotinib may improve efficacy by blocking multiple components of the same pathway. We conducted a phase I study to determine feasible dosages of combination therapy with erlotinib and everolimus for previously treated metastatic or unresectable NSCLC. Methods: Participants had advanced NSCLC progressing after two or less previous chemotherapy regimens. Feasibility of daily/weekly everolimus plus daily erlotinib was determined using a 6 + 6 dose-escalation design based on the rate of dose-limiting toxicities. Antitumor activity was assessed by the Response Evaluation Criteria In Solid Tumors study. Results: Of the 94 patients enrolled, 90% had stage IV NSCLC, 19% never smoked, and 15% were current smokers. Eighty-nine patients experienced one or more adverse events possibly related to any study medication. The most common dose-limiting toxicities were stomatitis (n = 5), rash (n = 4), and diarrhea (n = 3). Maximum tolerated doses were everolimus 5 mg per day or 50 mg per week plus erlotinib 150 mg per day. In daily everolimus cohorts (n = 74), nine patients achieved a complete/partial response and 28 had stable disease (median duration disease control, 9.3 months). In weekly everolimus cohorts (n = 20), no tumor response was observed; seven patients had stable disease (median duration, 9.6 months). Conclusions: Combination therapy with everolimus 5 mg per day or 50 mg per week and erlotinib 150 mg per day provided acceptable tolerability and disease control. A randomized phase II study evaluating this combination in comparison with erlotinib alone is complete and is being analyzed.
引用
收藏
页码:1594 / 1601
页数:8
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