Randomized Phase II Study Comparing Two Schedules of Everolimus in Patients With Recurrent/Metastatic Breast Cancer: NCIC Clinical Trials Group IND.163

被引：221

作者：

Ellard, Susan L. ^{[1
]}

Clemons, Mark ^{[1
]}

Gelmon, Karen A. ^{[1
]}

Norris, Brian ^{[1
]}

Kennecke, Hagen ^{[1
]}

Chia, Stephen ^{[1
]}

Pritchard, Kathleen ^{[1
]}

Eisen, Andrea ^{[1
]}

Vandenberg, Ted ^{[1
]}

Taylor, Marianne ^{[1
]}

Sauerbrei, Eric ^{[1
]}

Mishaeli, Moshe ^{[1
]}

Huntsman, David ^{[1
]}

Walsh, Wendy ^{[1
]}

Olivo, Martin ^{[1
]}

McIntosh, Lynn ^{[1
]}

Seymour, Lesley ^{[1
]}

机构：

[1] BC Canc Agcy So Interior, Kelowna, BC V1Y 5L3, Canada

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2009年 / 27卷 / 27期

关键词：

ADVANCED SOLID TUMORS; RENAL-CELL CARCINOMA; MAMMALIAN TARGET; INHIBITOR TEMSIROLIMUS; RAPAMYCIN; MTOR; TOXICITY; THERAPY; CCI-779; PATHWAY;

D O I：

10.1200/JCO.2008.21.3033

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose To evaluate the safety and efficacy of oral everolimus, a mammalian target of rapamycin (mTOR) inhibitor, in two different schedules in minimally pretreated patients with metastatic breast cancer and to explore for possible biologic correlates of response. Patients and Methods Patients who received no or one prior chemotherapy regimen for metastatic breast cancer were entered onto this multicenter, noncomparative, randomized phase II study of everolimus 10 mg daily versus 70 mg weekly; the multinomial end points of response and progression were evaluated at 8 weeks. A two-stage accrual design was used, with 15 evaluable patients in each schedule in stage 1. Only daily therapy met criteria for continuing, and another 15 patients were added. pAKT, PTEN, carbonic anhydrase 9, estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) were evaluated for possible correlation with response. Results The most common drug-related toxicities were fatigue, rash, anorexia, diarrhea, stomatitis, cough, and pneumonitis. Pneumonitis occurred at higher than expected rates and seemed to be schedule dependent, with the highest incidence on the daily schedule. Response rate with daily therapy was 12% (95% CI, 3.4% to 28.2%) compared with 0% (95% CI, 0.0% to 20.6%) for weekly therapy. Twenty-seven percent of patients on daily therapy discontinued treatment compared with 13% on weekly therapy (16% v 6% with pneumonitis, respectively). No biologic correlates of response could be identified, although there were trends favoring benefit in ER-positive and HER2-negative metastatic breast cancer. Conclusion Oral everolimus has activity in metastatic breast cancer that is schedule dependent. Daily therapy with 10 mg is worthy of further study in this patient population. J Clin Oncol 27:4536-4541. (C) 2009 by American Society of Clinical Oncology

引用

页码：4536 / 4541

页数：6

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