WASHINGTON--The FDA’s On-cology Drugs Advisory Committee (ODAC) has recommended full approval of Rhône-Poulenc Rorer’s Taxotere (docetaxel) and a widening of the advanced breast cancer indication that received conditional approval in 1996, subject to completion of phase III trials.
WASHINGTON--The FDAs On-cology Drugs Advisory Committee (ODAC) has recommended full approval of Rhône-Poulenc Rorers Taxotere (docetaxel) and a widening of the advanced breast cancer indication that received conditional approval in 1996, subject to completion of phase III trials.
The 1996 approval was for the treatment of patients with locally advanced or metastatic breast cancer who have progressed during anthracycline-based therapy or relapsed during anthracycline-based adjuvant therapy. The new indication eliminates references to anthra-cycline and allows use "after failure of previous chemotherapy."
Editor's Note: Shortly after the ODAC meeting, the FDA gave full approval for Taxoteres expanded indication.
The new indication is based on two studies, TAX 304 and 303. TAX 304, a nonblinded, randomized, multicenter, phase III study, compared Taxotere with mitomycin/vinblastine (MV) in metastatic breast cancer patients who had failed an anthracycline-containing regimen.
The company reported a complete response rate of 3.4% (vs 1.6% for MV) and a partial response rate of 26.6% (vs 10.1% for MV). Time to progression (the primary endpoint) on Taxotere was 19 weeks vs 11 weeks for MV. The company also cited 1-year survival of 49% for Taxotere vs 33% for MV, and 18-month survival of 33% vs 21%, respectively.
Time to Progression
The FDA reviewers adjusted the time to progression results to 17 weeks and 10 weeks, respectively, but said the difference was still statistically valid. The agency also acknowledged statistically significant superior results in median survival and response rate. However, they did express concerns that there were fewer patients with multiple organ involvement in the Taxotere arm and about protocol adherence to follow-up assessments.
TAX 303 was a phase III, randomized, multicenter trial of Taxotere vs doxorubicin in patients with metastatic breast cancer who had failed a regimen containing an alkylating agent. The company reported a higher response rate for Taxotere (48% vs 33% for doxorubicin).
FDA medical officer Judy Beitz, MD, agreed that the response rate was higher with Taxotere than doxorubicin. But she also said that the prognostic factors favored the Taxotere arm; that no statistical differences were found between arms in time to progression, median survival, or duration of response; and that quality of life was not improved.