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Becky
1: J Clin Oncol. 2002 Feb 1;20(3):719-26. Links
Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer.
Vogel CL,
Cobleigh MA,
Tripathy D,
Gutheil JC,
Harris LN,
Fehrenbacher L,
Slamon DJ,
Murphy M,
Novotny WF,
Burchmore M,
Shak S,
Stewart SJ,
Press M.
University of Miami School of Medicine, Comprehensive Cancer Research Group Inc, and Columbia Cancer Research Network of Florida, Miami, FL, USA.
PURPOSE: To evaluate the efficacy and safety of first-line, single-agent trastuzumab in women with HER2-overexpressing metastatic breast cancer. PATIENTS AND METHODS: One hundred fourteen women with HER2-overexpressing metastatic breast cancer were randomized to receive first-line treatment with trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg weekly, or a higher 8 mg/kg loading dose, followed by 4 mg/kg weekly. RESULTS: The objective response rate was 26% (95% confidence interval [CI], 18.2% to 34.4%), with seven complete and 23 partial responses. Response rates in 111 assessable patients with 3+ and 2+ HER2 overexpression by immunohistochemistry (IHC) were 35% (95% CI, 24.4% to 44.7%) and none (95% CI, 0% to 15.5%), respectively. The clinical benefit rates in assessable patients with 3+ and 2+ HER2 overexpression were 48% and 7%, respectively. The response rates in 108 assessable patients with and without HER2 gene amplification by fluorescence in situ hybridization (FISH) analysis were 34% (95% CI, 23.9% to 45.7%) and 7% (95% CI, 0.8% to 22.8%), respectively. Seventeen (57%) of 30 patients with an objective response and 22 (51%) of 43 patients with clinical benefit had not experienced disease progression at follow-up at 12 months or later. The most common treatment-related adverse events were chills (25% of patients), asthenia (23%), fever (22%), pain (18%), and nausea (14%). Cardiac dysfunction occurred in two patients (2%); both had histories of cardiac disease and did not require additional intervention after discontinuation of trastuzumab. There was no clear evidence of a dose-response relationship for response, survival, or adverse events. CONCLUSION: Single-agent trastuzumab is active and well tolerated as first-line treatment of women with metastatic breast cancer with HER2 3+ overexpression by IHC or gene amplification by FISH.
PMID: 11821453 [PubMed - indexed for MEDLINE]
So for her2 2+ and 3+ 35% had an objective response and of her2 + by FISH 34% had a response--but 48% had clinical benefit ie, not that the tumor(s) got smaller but that they didn't progress, I believe.
This is the only published study I believe on herceptin monotherapy ie, herceptin given without previous or concurrent chemo and was only done in the metastatic setting.
(Remember that IHC and FISH testing is not done equally well everywhere.)
IT seems about 50-60% of those who responded or got benefit (stayed stable) had a "long" lasting benefit ie, did no progress for the intervening 12 months at least.
Drs. Spector and Baccus have published articles implying that herceptin resistance can develop in double/triple/positives if an antihormonal of some type is not given. Dr. Dennis Slamon believes, theoretically at least, that fulvestrant should be the most effective in her2+ patients, but it is only available in the metastatic setting for those who have failed previous antihormonals
Hope this help!
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Hybrid Mode
