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Title: Interim Combined Analysis Shows Benefits of Adjuvant trastuzumab (Herceptin) in HER2-Positive Early Breast Cancer: Presented at IBCEF

"Interim Combined Analysis Shows Benefits of Adjuvant trastuzumab (Herceptin) in HER2-Positive Early Breast Cancer: Presented at IBCEF"

By Chris Berrie VIENNA, AUSTRIA -- February 20, 2006 -- Adjuvant trastuzumab (Herceptin(R)) is recommended for patients with HER2-positive early breast cancer if there are no specific contraindications, and it can be administered concomitantly with radiotherapy, according to an interim combined analysis of two multicentre, randomised phase 2 trials. The analysis combined data from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B31 trial and the North Central Cancer Treatment Group (NCCTG) N9831 trial. Edith Perez, MD, Professor of Medicine and Director of Cancer Clinical Study Unit, Division of Haematology/ Oncology, Mayo Clinic, Jacksonville, Florida, United States, discussed the rationale for the combined analysis of these two National Cancer Institute sponsored trials of adjuvant trastuzumab therapy, saying that their similar control and concurrent treatment groups compared standard chemotherapy (doxorubicin/cyclophosphamide 60/ 600 mg/m[² 3 times weekly for 4 cycles; AC) followed by paclitaxel (P) with or without concurrent trastuzumab.

Dr. Perez made her presentation here on February 11^th at the International Breast Cancer Expert Forum: Milestones in Management, Confidence and Care (IBCEF), sponsored by Roche.

The combined control arm (AC-P; n = 1679) comprised Arm 1 of NSABP-B31 (n = 872) of AC followed by paclitaxel at 175 mg/m² 3-weekly for 4 cycles plus Arm A of NCCTG N9831 (n = 807) of AC followed by paclitaxel at 80 mg/m² weekly for 12 weeks.

The combined trastuzumab arm (AC-PT; n = 1672) comprised Arm 1 of B31 and Arm A of N9831, each plus trastuzumab 4 mg/kg loading dose after AC, and 2 mg/kg per week for 51 weeks (i.e. Arm 2 of B31 [B31-trastuzumab; n = 864] and Arm C of N9831 [N9831-trastuzumab; n = 808]).

This combined analysis resulted in a total population of 3351 patients with HER2-positive early breast cancer, with similar baseline patient demographics across these combined treatment groups for age, number of positive nodes, and hormone receptor status.

At a median follow-up of 2 years, this combined analysis showed a significant benefit of trastuzumab (AC-PT) over AC-P for disease-free survival (DFS) of 85% versus 67% (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.39-0.59; P < .0001). Dr Perez also indicated that this significant improvement in DFS for AC-PT was seen across all subgroups analysed, which included tumour size and per protocol, although it was lost for the patients with no positive nodes.

For time to first distant recurrence, there were significant improvements seen in the trastuzumab group versus paclitaxel -- 90% and 74% (HR, 0.47; 95% CI, 0.37-0.61; P < .0001). This was also the case for overall survival -- 91% and 87% (HR, 0.67; 95% CI, 0.48-0.93; P = .015), respectively.

For B31, there were 36 cardiac events reported in the two treatment arms -- one cardiac death and 35 cases of congestive heart failure (CHF). Three years post-AC saw a cumulative incidence of 0.8% for B31 controls, and 4.1% for B31-trastuzumab. For N9831, the 3-year cumulative incidence was based on a total of 39 cardiac events (across the three arms) -- two cardiac deaths and 37 CHFs, with 0.3% for N9831 controls and 3.5% for N9831-trastuzumab patients.

Dr. Perez stressed that, overall, the risk of cardiac events for trastuzumab versus non-trastuzumab was low, at less than 4%.

In terms of the relationships between the cumulative incidence of CHF and LVEF post-AC with respect to the age across the B31 and N9831 trials, Dr. Perez indicated that there may be an increased risk of cardiac events with age. The data from N9831 also demonstrated that radiotherapy does not increase the incidence of cardiac events.

Thus, Dr. Perez summarised by saying that this combined analysis from the two trials demonstrates that trastuzumab given concurrently with paclitaxel following doxorubicin/cyclophosphamide significantly improves disease free survival, reduces recurrence, while improving overall survival.

Although this treatment is associated with a low risk of cardiac events and can be recommended for patients with HER2-positive early breast cancer who show no specific contraindications, there remains the need for the careful monitoring of their cardiac function, she concluded.

The conference was sponsored by Roche.

REFERENCE:
Romond et al. N Engl J Med. 353(16):1673-1684.

[Presentation title: NSABP-B31/NCCTG N9831: Interim Combined Analysis.]

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