Phase I Study of Everolimus Plus Weekly Paclitaxel and Trastuzumab in Patients with Metastatic Breast Cancer Pretreated with Trastuzumab

Fabrice Andre, Mario Campone, Ruth O'Regan, Corinne Manlius, Cristian Massacesi, Tarek Sahmoud, Pabak Mukhopadhyay, Jean Charles Soria, Michael Naughton, Sara A. Hurvitz

Research output: Contribution to journalArticlepeer-review

180 Scopus citations


Purpose: To determine the recommended dose of everolimus, a mammalian target of rapamycin inhibitor, combined with paclitaxel and trastuzumab in patients with human epidermal growth factor receptor 2 (HER2) - overexpressing metastatic breast cancer pretreated with trastuzumab. Methods: In this phase Ib, multicenter, dose-escalation study, patients were treated with everolimus 5 mg/d, 10 mg/d, or 30 mg/wk in combination with paclitaxel (80 mg/m2 days 1, 8, and 15 every 4 weeks) and trastuzumab (2 mg/kg weekly). End points included end-of - cycle 1 dose-limiting toxicity (DLT) rate (primary end point), safety, relative dose intensity of study drugs, overall response rate (ORR), and pharmacokinetics. Results: Of 33 patients enrolled, 31 were pretreated with taxanes, and 32 were resistant to trastuzumab. Patients received a median of two lines of chemotherapy in the metastatic setting (range, 0 to 17 lines). Three patients experienced cycle 1 DLTs: febrile neutropenia (5 mg/d), stomatitis (10 mg/d), and confusion (30 mg/wk). Grade 3 to 4 neutropenia was the most common toxicity observed (n = 17 patients [52%]). On the basis of observed DLTs and overall safety, 10 mg/d was recommended for additional development. Twenty-seven patients had measurable disease and were evaluable for efficacy. Among these patients, ORR was 44%. Overall disease was controlled for 6 months or more in 74%. Median progression-free survival was 34 weeks (95% CI, 29.1 to 40.7 weeks). Among 11 patients who were resistant to both trastuzumab and taxane, a similar level of antitumor activity was observed (ORR, 55%). Conclusion Everolimus combined with weekly paclitaxel and trastuzumab was generally well tolerated and had encouraging antitumor activity in patients with trastuzumab-pretreated and -resistant metastatic HER2-overexpressing breast cancer.

Original languageEnglish
Pages (from-to)5110-5115
Number of pages6
JournalJournal of Clinical Oncology
Issue number34
StatePublished - Dec 1 2010


Dive into the research topics of 'Phase I Study of Everolimus Plus Weekly Paclitaxel and Trastuzumab in Patients with Metastatic Breast Cancer Pretreated with Trastuzumab'. Together they form a unique fingerprint.

Cite this