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a timely medical meeting newsletter
HER-2 MONOCLONAL ANTIBODIES HELP CHEMOTHERAPY IN BREAST CANCER
| D.J. Slamon, MD, PhD, University of California-Los Angeles School of Medicine, found antibodies to the human epidermal growth factor receptor (HER-2) additive in treating breast cancer patients. Combined use of HER-2 antibodies (H) with cyclophosphamide/doxorubicin or paclitaxel improved time to disease progression (TTP) by 4 months and overall response rate (RR) by 26%. Of concern is the more frequent occurrence of grade 3/4 cardiomyopathy with combined therapy. This well-controlled, multicenter trial in 469 high-risk women provides a rationale for future combination studies. | |
| Introduction to Phase III trial | Slamon et al correlated relapse and poor survival in primary human
breast cancers showing amplified HER-2/neu oncogenes (Science 1987;235;
177). The 189 sampled patients had a positive rate of 28%. Two or more
copies of the tumor deoxyribonucleic acid (DNA) shortened median survival
based on the Kaplan-Meier method (Science 1989;244:707). The results of
these studies led to preparation and purification of rhu Mab HER2
antibodies (H) for clinical evaluation.
Baselga et al conducted a Phase II study in women with metastatic disease including overexpressed HER-2 (J Clin Oncol 1996;14:737). Five of 43 evaluable patients showed remissions (1 complete and 4 partial) after an iv loading dose of 250 mg H plus 100 mg weekly for 10 weeks. Toxicity in 46 recipients after 768 administrations included moderate fever and chills (5/46), pain at tumor site (2/46), diarrhea (2/46), and nausea/ vomiting (1/46). One patient reported severe pain at the tumor site. |
| Controlled trial methodology |
Eligible cancer patients had to have HER-2 overexpression using
immunohistochemistry, a Karnofsky normal function score of 60 or more,
no prior stage 4 chemotherapy, and measurable disease. The 469 patients
entering the multicenter trial were assigned randomly to take
chemotherapy alone or combined with HER-2 antibodies. Among the measured
response variables were: TTP as determined by an independent evaluation
group, RR, duration of response, 1-year survival, quality of life (QoL),
and adverse drug events (ADEs).
The patients received one of two chemotherapy regimens every 3 weeks for six cycles with or without added antibodies (H):
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| Results of treatment at 12 months |
Slamon reported statistically significant improvement comparing test and
control patients:
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| Adverse drug events in H-treated women | Preliminary analyses show leukopenia and anemia occurred more frequently in H-treated patients. More women also developed grade 3/4 cardiomyopathy, 20% vs 3%, but responded favorably to ACE inhibitors, diuretics, or an occasional inotrope, according to Slamon. Combining chemotherapy with H monoclonal antibodies was well tolerated according to this double-blind, multicenter, multinational trial in 469 evaluable patients. |
Presented at the American Society of Clinical Oncology (ASCO) Meeting,
May 16-19, 1998
Copyright © 1998 Conrad Group Inc. All Rights Reserved
Eugene A. Conrad, PhD, MPH / ISSN 1078-2230 / June 1998
Send Comments to: ConradNote@aol.com
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