Weekly Combination Therapy Safe for HER2+ Breast Cancer

Jane Salodof MacNeil

December 05, 2003

Dec. 5, 2003 (San Antonio) — Paclitaxel, carboplatin, and trastuzumab administered together in weekly doses greatly reduced toxicity for women with HER2-positive metastatic breast cancer, according to final results from a set of randomized phase II trials conducted by the North Central Cancer Treatment Group (NCCTG).

The weekly schedule also appeared to be slightly more effective than the standard practice of giving paclitaxel and carboplatin every three weeks. The overall response rate was 71% vs. 65% for patients on the three-week schedule.

"Both regimens are very active, but tolerability favors the weekly regimen. This is the best regimen to choose for HER2-positive breast cancer," said investigator Edith A. Perez, MD, from the Mayo Clinic in Jacksonville, Florida. She spoke at a presentation during the 26th Annual San Antonio Breast Cancer Symposium.

The concurrent trials randomized 91 women with HER2-positive tumors. One group of 43 women received 200 mg/m2 of paclitaxel and carboplatin AUC 6 every three weeks with 8 mg/kg (and then 6mg/kg) of trastuzumab administered on the first day for six months.

The other 48 women were given 80 mg/m2 of paclitaxel and carboplatin AUC 2 weekly for three weeks followed by a rest week along with weekly trastuzumab for six months. Both groups continued receiving trastuzumab until progression.

Most of the women were postmenopausal (77% of the three-week group and 81% of the weekly group). More women on the weekly regimen had visceral metastases as the dominant disease: 84% vs. 67%.

The results for grades 3 and 4 toxicities, both hematologic and nonhematologic, demonstrated dramatic benefits for women on the weekly schedule.

Only 12% had grade 4 neutropenia compared with 67% of the women on the three-week schedule. No other grade 4 toxicities occurred in the weekly combination group, but 14% of the other group had grade 4 leukopenia, 2% had grade 4 febrile neutropenia, and 5% had grade 4 hypersensitivity.

The weekly schedule also had the advantage in most grade 3 toxicities, including leukopenia (33% vs. 56%), thrombocytopenia (5% vs. 30%), febrile neutropenia (2% vs. 14%), neurosensory (2% vs. 19%), myalgia (2% vs. 14%), and arthralgia (5% vs. 12%).

The median response duration was 12.5 months for the weekly group and 9.9 months for the three-week group, and patients are still responding, Dr. Perez said. No statistical analysis was made for efficacy, she said, because that would have required a phase III trial with hundreds of women.

Sankari Sivasartan, MD, a radiation oncologist in private practice in Baltimore, Maryland, said the efficacy of both regimens meant that physicians could give either regimen to patients who travel long distances for treatment. "It's very applicable in clinical practice," she said.

Michael DiGiovanna, MD, from Yale University School of Medicine in New Haven, Connecticut, also said the results would apply to a large number of patients. Despite the better results for weekly dosing, he saw the results validating the three-week regimen as well. "If it's a matter of convenience for a patient to come for treatment less often, that's an option as well, with a little more toxicity but tolerable efficacy," he said.

26th Annual SABCS: Abstract 216. Presented Dec. 4, 2003.

Reviewed by Gary D. Vogin, MD

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