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BCIRG 006 Shows Trastuzumab (Herceptin) Improves Disease-Free Survival and Overall Survival for HER2-Positive Early Breast Cancer: Presented at IBCEF

By Chris Berrie

VIENNA, AUSTRIA -- February 20, 2006 -- Adjuvant trastuzumab (Herceptin) provides significant benefit for patients with HER2-positive early breast cancer, with a favourable safety profile and risk:benefit ratio, according to a multicentre, randomised trial presented here February 11^th at the International Breast Cancer Expert Forum: Milestones in Management, Confidence and Care (IBCEF).

Tadeusz Pienkowski, MD, oncologist, department of breast cancer and reconstruction surgery, Cancer Centre, Warsaw, Poland, presented this 3-arm Breast Cancer International Research Group (BCIRG) 006 adjuvant trial that compared a docetaxel with carboplatin and trastuzumab (DCT; 6 cycles, with 1 year of trastuzumab) regimen with doxorubicin/cyclophosphamide (AC; 4 cycles) followed by docetaxel (4 cycles) without (AC-D) and with (AC-DT) trastuzumab for 1 year.

Inclusion criteria were early node-positive breast cancer, or high-risk node-negative breast cancer, and human epidermal growth factor receptor 2 (HER2)-positive status. The 3222 patients enrolled were stratified according to hormone receptor status.

Baseline patient characteristics for each of the 3 arms (AC-D, n = 1073; AC-DT, n = 1074; DCT, n = 1075) were similar for age < 50 years (52%, 52%, 54%, respectively), Karnofsky performance status (80, 79, 80), and prior treatment, including mastectomy (60%, 63%, 60%), radiotherapy (59%, 58%, 60%), and hormone therapy (47%, 47%, 49%). Tumour characteristics were also similar across nodal status, tumour size, and estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+).

After 4 years in the trial, disease-free survival (DFS) for the AC-D arm was 73%, and there were significant improvements over this for both DCT (80% DFS; hazard ratio [HR], 0.61) and AC-DT (84% DFS; HR, 0.49). Mortality rates also favoured AC-DT (1.9%) over AC-D (3.4%) and DCT (2.6%).

Safety profiles for grade 3/4 haematological toxicity were similar across these 3 regimens, with most seen in no more than 10% of patients, except for the preponderance of neutropenia (65% of patients) and leukopenia (50%). For the grade 3/4 nonhaematological toxicity, most were seen in 2% to 6% of patients, except for irregular menses (20%).

With the same median age of 49 years across the 3 groups, Dr. Pienkowski described their full profile of cardiovascular risk factors, indicated their generally similar levels of patients with diabetes (3.5%, 3.2%, 2.8%, respectively), hypercholesterolaemia (5.0%, 4.2%, 4.0%, respectively), hyperlipidaemia (1.9%, 0.9%, 1.1%, respectively), obesity (2.5%, 3.4%, 3.4%, respectively), and hypertension (1.5%, 1.5%, 1.6%, respectively).

Similarly, the number of patients who had undergone radiotherapy after chemotherapy (59.5%, 58.2%, 60.2%) was well balanced across the 3 groups.

Dr. Pienkowski then detailed the analysis of the clinically significant cardiac events. There were no significant differences between the AC-D and DCT groups (P = .54), with 0.95% (95% confidence interval [CI], 0.46-1.74) and 1.33% (95% CI, 0.73-2.21) of patients showing such events. This was also the case between the DCT and AC-DT groups (P = .11), with 2.34% (95% CI, 1.52-3.44) in the latter. However, the increase in cardiac events seen with AC-DT over AC-D did reach statistical significance (P = .016).

Some of these data are at present under the further review of an independent review panel.

Along with a chromosomal analysis of the HER2 core region at 17q21.1, to date, some 66% of these patients have also been analysed for potential co-amplification of the topoisomerase II region (TopoII; 17q21.2). Of these, 60% remain normal for TopoII, while 4% show a TopoII deletion and 35% show its co-amplification with HER2.

There was a significantly improved DFS for the co-amplified TopoII patients (744 patients; 57 events) over the non-co-amplified TopoII patients (1376 patients; 191 events; P < .001), Dr. Pienkowski noted.

This 3-arm trial has thus demonstrated significant benefits of trastuzumab use for patients with HER2-positive early breast cancer, he concluded, accompanied by a favourable safety profile with few cardiac events, providing a risk:benefit ratio that warrants the use of trastuzumab.

However, Dr. Pienkowski indicated the need for further follow-up to determine whether there are efficacy and safety differences between the 2 arms that included trastuzumab.

This conference was sponsored by Roche.

REFERENCE:
Slamon et al. BCIRG 006, 1^st Interim Analysis on Efficacy and Safety. San Antonio Breast Cancer Symposium 2005.


[Presentation title: BCIRG 006.]

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