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1298
A Phase II Trial of Herceptin Alone and with
Taxol for the Treatment of Prostate Cancer. Michael J.
Morris, Victor E. Reuter, William K. Kelly, Susan F. Slovin, Katie
I. Kenneson, Iman Osman, David Agus, Howard I. Scher, Memorial
Sloan-Kettering Cancer Ctr, New York, NY.
Herceptin (H) is a monoclonal antibody directed at the
extracellular domain of the HER2 gene product that has been shown to
improve survival in patients (pts) with HER2+ breast cancer. The
antitumor effects of H varied according to hormonal status when used
in a HER2+ prostate cancer xenograft model (Cancer Res. 59:4761-4,
1999). The aims of this study were to determine the efficacy of
weekly H at 2 mg/kg (after a 4 mg/kg loading dose) alone and in
combination with Taxol (T) for progressive prostate cancers, and to
explore associations between HER2 expression and clinical outcome.
Tumors were stratified as androgen-dependent (AD) or androgen
independent (AI), and by HER2 status. Pts were initially treated
with H alone. Those with stable disease or better at 12 weeks
continued with H alone, otherwise weekly T at 100 mg/m2
was added. HER2 expression in 93 tumor samples (76 prostates and 17
metastases) was studied, 12% of which were HER2+. Breakdown by site:
of the prostate samples, 9% of 67 AD samples were HER2+ and zero of
9 AI samples were HER2+. Of the metastases, 14% of 7 AD samples were
HER2+ and 40% of 10 AI samples were HER2+. There were 8 matched
pairs, including 3 cases in which AI metastases were HER2+ and the
AD primaries were HER2-; 5 pairs were concordant as HER2-. 21
patients (2 AD and 19 AI) have been treated to date. 12 of 14 AI
HER2- pts (2 are too early) progressed on monotherapy and 9 received
combination therapy but did not respond. 4 of 5 HER2+ AI pts (1 is
too early) have progressed on monotherapy and 3 received T. 2 showed
clinical benefit with T. Both AD pts are too early to evaluate.
Grade 3/4 toxicities attributable to H alone were hyperglycemia (1
pt) and fatigue (1 pt); grade 3/4 toxicities seen with the addition
of T were hyperglycemia (4 pts), anemia (1 pt), and leukopenia (2
pts). Our preliminary data suggest that H alone is inactive for the
treatment of AI HER2- tumors. Accrual of pts with HER2+ tumors
continues. The documentation of discordant immunohistochemistry
results in HER2- AD vs. HER2+ AI tumors from the same patient
requires additional study, but suggests that profiling of HER2
status should include an evaluation of the AI tumor. Support:
Genentech, CA09207, CA05826
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