RAD001 Shows Promise In Tough-to-Treat Breast Cancer Patients

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Main Category: Breast Cancer
Also Included In: Cancer / Oncology;  Clinical Trials / Drug Trials
Article Date: 13 Dec 2008 - 0:00 PDT

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SAN ANTONIO - Investigators are reporting favorable early results using RAD001 (Afinitor) combined with weekly paclitaxel and trastuzumab to treat patients with HER-2 overexpressing metastatic breast cancer who have demonstrated prior resistance to trastuzumab.

The results, released here at the 2008 San Antonio Breast Cancer Symposium (SABCS), show that RAD001 combined with trastuzumab and chemotherapy halted tumor growth in 77 percent of patients.

Ruth O'Regan, MD, associate professor of hematology and oncology at Emory University in Atlanta, Georgia, and associates elsewhere presented data in 22 heavily pre-treated patients who received RAD001 in tandem with weekly paclitaxel and trastuzumab as part of an ongoing phase 1 trial. All patients were resistant to trastuzumab and all but one had had received prior taxane treatment.

The study follows preclinical research showing that the oral mTOR inhibitor RAD001 enhances the efficacy of trastuzumab, thereby suggesting that RAD001 might reverse resistance to trastuzumab.

For the trial, paclitaxel (80 mg/m2) IV was administered over 60 minutes on days one, eight, and 15 every four weeks. Trastuzumab, 4 mg/kg loading dose was administered IV over 90 minutes on day one (if the patient was not already receiving trastuzumab), followed by weekly 2 mg/kg IV over 30 minutes. RAD001 was administered as either daily ( 5 and 10 mg) or weekly (30, 50, and 70 mg). Treatment was continued until there was evidence of disease progression or unacceptable toxicity.

Six of the 22 patients in whom data were available had received the 5 mg daily dose of RAD001, six had received the 10 mg daily dose, and 10 had received the 30 mg weekly dose. The median number of prior regimens was six.

Two dose-limiting toxicities were recorded during the first cycle, which included febrile neutropenia on the daily 5 mg arm and confusional state on the weekly 30 mg arm.

A high rate of tumor responses was observed in the 17 patients in whom efficacy data were available. Five (77 percent) of the seven patients resistant to both trastuzumab and herceptin had partial response (four of five patients on the 5 mg daily and one of two patients on the 30 mg weekly cohort). Of these patients, two had stable disease for more than 16 weeks.

Elsewhere at the meeting, investigators reported updated data from a second phase 1 study demonstrating promising anticancer activity for RAD001 combined with tratuzumab and vinorelbine in heavily pretreated trastuzumab-resistant patients with HER2-positive metastatic breast cancer. That is, RAD001 in combination with trastuzumab and vinorelbine halted tumor growth in 62% of patients.

A spokesperson for Novartis, which developed RAD001, said that the data support the initiation of a phase III program in order to comprehensively examine a possible role for RAD001 in breast cancer.

Written by Jill Stein
Jill Stein is a Paris-based freelance medical writer.
jillstein03(at)gmail.com


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