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Patients with metastatic breast cancer may benefit from combination therapy with everolimus
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Nearly three-quarters of patients with metastatic breast cancer who were treated with combination therapy using everolimus achieved clinical benefit, according to study results.
The aim of the study was to determine the recommended dose of everolimus with paclitaxel and trastuzumab for treating patients with overexpressed HER-2 metastatic breast cancer — defined as a score of 3+ by immunohistochemistry and/or amplification by fluorescence in situ hybridization — and who had been pretreated with trastuzumab.
There were 33 patients from several sites initially enrolled in the phase 1b dose-escalation study. Thirty-one of those patients were pretreated with taxanes and 32 were resistant to trastuzumab.
The treatment regimens were everolimus at 5 mg daily, 10 mg daily or 30 mg weekly with paclitaxel at 80 mg/m2 on days 1, 8 and 15 every 4 weeks and trastuzumab at 2 mg/kg weekly. Treatment lasted a median of 28 weeks in the 5-mg and 10-mg daily everolimus cohorts and 33 weeks in the 30-mg weekly everolimus cohort.
The primary outcome measure was the end-of-cycle one dose-limiting toxicity rate. Other endpoints included safety, relative dose intensity of study drugs, overall response rate and pharmacokinetics.
In the metastatic setting, participants received a median of two lines of chemotherapy (range, 0 to 17 lines).
During cycle one, dose-limiting toxicities were experienced by three patients including febrile neutropenia (in a patient in the 5-mg daily group), stomatitis (a patient in the 10-mg daily group) and confusion (a patient in the 30-mg weekly group). More than half (52%) of the patients experienced grade 3 to 4 neutropenia.
In a group of 27 patients who were evaluated for efficacy in the final analysis, the overall response rate was 44%, the disease control rate was 93% and the clinical benefit rate (defined as overall disease control for 6 months or more) was 74%.
Similar levels of antitumor activity were observed among 11 patients who were resistant to trastuzumab and taxane (overall response rate, 55%).
The researchers noted that better outcomes were observed in the 5-mg daily group vs. the other two treatment groups, and that this may be due to more favorable baseline characteristics among those patients.
The median PFS period was 34 weeks (95% CI, 29.1-40.7).
For more information:
- Andre F. J Clin Oncol. 2010;doi:10.1200/JCO.2009.27.8549.