Everolimus May Help Thwart Trastuzumab Resistance In Breast Cancer Patients

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Main Category: Breast Cancer
Also Included In: Cancer / Oncology;  Clinical Trials / Drug Trials
Article Date: 08 Oct 2009 - 11:00 PDT

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BERLIN - New data identify a possible role for everolimus in reversing or delaying the onset of trastuzumab resistance in breast cancer patients.

The findings are from two trials presented at the joint 15th European Cancer Organization (ECCO) and 34^th European Society for Medical Oncology (ESMO) Multidisciplinary Congress.

Everolimus is an oral mTOR inhibitor that is approved for the treatment of patients with advanced renal cell carcinoma whose disease has progressed on or after treatment with vascular endothelial growth factor-targeted therapy.

The drug has also been shown to reverse trastuzumab resistance caused by PTN loss in preclinical studies and additionally has shown anti-tumor activity as a single agent in patients with metastatic breast cancer.

Dr. Sara Hurvitz, with the UCLA School of Medicine, and colleagues conducted a study to establish the feasible dose schedule for daily and weekly administration of everolimus combined with weekly trastuzumab and paclitaxel in patients with HER-2 overexpressing metastatic breast cancer whose disease had progressed during or after trastuzumab therapy.

Results in 33 patients showed that the combination was well tolerated and that the recommended starting dose for the phase II study is 10 mg daily.

Combination therapy involving everolimus, paclitaxel, and trastuzumab demonstrated "encouraging" efficacy in this heavily treated population of patients refractory to trastuzumab and taxanes. In particular, everolimus demonstrated activity in all patients who were evaluable for efficacy and assigned to the 5 mg everolimus treatment group.

The disease control rate was 85% (28 of 33 evaluable patients).

Biomarker results were similar to those observed during everolimus monotherapy in patients with metastatic renal cell cancer and suggest that the activity of everolimus is mediated in part through inhibition of VEGF-A-driven angiogenesis, Dr. Hurvitz said.

In a second study, similar results were obtained with the combination of everolimus (5 mg daily or 20 or 30 mg weekly) with vinorelbine and trastuzumab.

Dr. Fatima Cardoso, with the Jules Bordet Institute in Brussels, reported that the combination was feasible and tolerable in a similar heavily pretreated group of breast cancer patients and also showed promising clinical activity with a relevant long-term disease control. The disease control rate was 80% (37 of 46 evaluable patients).

In the study, there was no limit to the number of prior antineoplastic treatments.

Overall, 30 patients were assigned to a 5 mg daily dose of everolimus, and 20 patients received a 20 or 30 mg weekly dose.

Dr. Cardoso said that the addition of everolimus can bolster the therapeutic activity of vinorelbine and trastuzumab and reverse or postpone the onset of trastuzumab resistance.

Written by Jill Stein
Jill Stein is a Paris-based freelance medical writer.
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