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.