Wyeth Pharmaceuticals, a division of Wyeth decided to discontinue the HORIZON phase 3 clinical trial program of Wyeth's investigational drug temsirolimus oral tablets in combination with letrozole (Femaraâ), a currently approved breast cancer therapy, for first-line use in postmenopausal women with hormone-receptor positive metastatic breast cancer. This decision was based upon the recommendation of an Independent Data Monitoring Committee (IDMC) after review of data from a planned interim analysis.
The HORIZON study compared the combination of temsirolimus oral tablets and letrozole versus letrozole alone. The IDMC advised that continuation of the trial was unlikely to achieve the targeted level of efficacy for the combination therapy compared to letrozole alone. The IDMC concluded, therefore, that the risk/benefit ratio for treatment of metastatic breast cancer did not favour continuation and recommended that the trial be discontinued, stated a company release.
"While not the anticipated outcome, it is unfortunately not unusual for cancer drugs to work in some tumor types and not others, or even work in only some specific subpopulations of cancer patients," says Gary L. Stiles, Executive Vice President and Chief Medical Officer, Wyeth Pharmaceuticals. "We remain committed to studying temsirolimus in other cancer indications," he added.
While the phase 3 trial for women with hormone-receptor positive metastatic breast cancer involved an oral formulation of temsirolimus, two other phase 3 clinical trials studying temsirolimus in renal cell carcinoma and mantle cell lymphoma using an intravenous formulation are continuing. After a recent review of the data, the IDMC for the renal cancer study indicated that study continue as planned.
Temsirolimus is a targeted investigational drug that specifically inhibits mTOR (mammalian target of rapamycin) kinase, a protein critical for tumour growth and cell survival. Enrollment continues as planned with other ongoing clinical trials with temsirolimus in the oncology setting.
In addition to Wyeth's ongoing renal cell carcinoma and mantle cell lymphoma phase 3 trials, independent investigators are evaluating temsirolimus in clinical trials in prostate cancer, and head and neck cancer. These and other early oncology trials with temsirolimus are being conducted through a cooperative research and development agreement with the National Cancer Institute. Anti-tumour activity with this agent has been previously reported in phase 1 and phase 2 studies.