Publication Year: 2000 Visited: 129

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Herceptin and Vinorelbine for HER2-Positive Metastatic Breast Cancer: A Phase II Study. Harold J. Burstein, Irene Kuter, Paul G Richardson, Susana M Campos, Leroy M Parker, Ursula A Matulonis, Lyndsay Harris, Judy E Garber, Jerry Younger, Craig A Bunnell, Lawrence N Shulman, Eric P Winer, Dana-Farber Cancer Institute, Boston, MA; MA Gen Hosp, Boston, MA.

Combined treatment with Herceptin (H) and chemotherapy improves response rates and survival in women with HER2-positive metastatic breast cancer (HER2+ MBC). Preclinical experiments suggest synergistic interactions between H and vinorelbine (V). A phase II study is being conducted to characterize the safety and efficacy of H and V as therapy for HER2+ MBC. Eligible women have measurable disease and ECOG PS 0-2. Tumors must be HER2+ (either +2 or +3) by IHC. The study opened as 2nd or 3rd line therapy for MBC; however, eligibility was later extended to 1st line. Patients cannot have received prior H. Treatment is H (4 mg/kg first dose, 2 mg/kg weekly thereafter) and V (25 mg/m2/week IV push). V dose is reduced to 15 mg/m2 for ANC 750-1250 or held if ANC < 750. Patients are restaged and cardiac function reassessed every 8 weeks. Forty patients have been enrolled into the trial, and results are presented for the first 34 patients who have completed at least one 8 week cycle. Median age: 51. Prior chemotherapy: adjuvant 56%, metastatic 62%, none 12%, anthracyclines (A) 62%, taxanes (T) 62%, both A and T 43%. Disease sites: visceral (liver and/or lung) 97%, liver 71%, lung 62%, bone 56%. To date, 707 weekly treatments have been given; median 21/pt. 98 treatments (14%) have required V dose adjustment. Treatment has been well tolerated. Neutropenia (grade 3 or 4, 29% of patients; 1 episode F&N) has been manageable without growth factor support. Sensory neuropathy (grade 1 or 2, 35%; grade 3 or 4, 0%), initial H infusion reactions (grade 1 or 2, 33%; grade 3 or 4, 0%), and constipation (grade 1 or 2, 15%; grade 3 or 4, 0%) have been reported. Two patients (6%) had grade 2 cardiac toxicity (asymptomatic with < 20% decrease in EF or EF < normal). Median TTP is 31 weeks. The overall response rate (RR) is 24 of 34 patients (71%; all PRs). Activity has been noted regardless of prior chemotherapy for metastatic disease (RR as 1st line therapy for MBC, 77%, 2nd line 60%, 3rd line 83%), and among patients with prior exposure to either A or T (RR 67%) or both A and T (RR 73%). These results suggest that combination therapy with H and V is active in women with HER2+ MBC, supporting pre-clinical data indicating synergy between these two agents. Support: NIH5T2 CA09172-24; Genentech.