more interim results from No. American and European (HERA) trials of herceptin

HERceptin Adjuvant Trial Results Suggest Benefits as Monotherapy in Adjuvant Setting: Presented at IBCEF [Doctor's Guide]
VIENNA, AUSTRIA — February 20, 2006 — Adjuvant trastuzumab (Herceptin(R)) as a single agent shows significant improvement in disease-free survival (DFS) and a clear trend towards improved overall survival with low incidence of severe congestive heart failure (CHF) in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, according to the HERceptin Adjuvant trial (HERA).

Richard Bell, MD, Senior Clinical Consultant, Professor and Director of Cancer Services, Medical Oncology, Andrew Love Cancer Centre, Geelong, Victoria, Australia, presented the HERA findings here on February 11th at the International Breast Cancer Expert Forum: Milestones in Management, Confidence and Care (IBCEF).

Trastuzumab is known to improve survival in women with metastatic breast cancer, Dr. Bell noted during his analysis of the international, multicentre, randomised study. Since HER2-positive breast cancer is associated with early progression and poor prognosis, the rationale for the HERA trial was to target the 25% of women with early breast cancer that have HER2-positive disease.

The HERA trial was designed to enrol patients with centrally confirmed HER2 overexpression or amplification who were node-positive or sentinel-node-negative, with a tumour diameter greater than 1.0 cm. Inclusion criteria also required completion of at least 4 cycles of a range of approved neoadjuvant chemotherapy regimen without or with radiotherapy, with or without anthracycline or taxane therapy. Finally, the patients needed to have a left ventricular ejection fraction (LVEF) of at least 55% and a known hormone status.

The primary efficacy endpoint was DFS, and secondary endpoints were time to recurrence, time to distant recurrence and overall survival. Safety endpoints were tolerability and general safety (including cardiac safety).

Although the HERA trial design provided for an observation arm and two trastuzumab 3 times weekly arms, for 1 year and 2 years of treatment, Dr. Bell presented the interim efficacy analysis after 475 events that considered observation and 1 year of trastuzumab treatment.

Patient age ranges for the observation (n = 1693) and trastuzumab (n = 1694) arms were well matched for age, prior neoadjuvant chemotherapy, postmenopausal status, hormone receptor status and nodal status.

At a median follow-up of 1 year, the observation arm had 220 events with a 2-year DFS of 77.4%, as compared 127 events in the 1-year trastuzumab arm, a significant reduction of 85.8% (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.43-0.67; P < .001).

Dr. Bell indicated that this benefit of trastuzumab were due largely to reduced distant events (85 vs. 154), locoregional events (27 vs. 50) and second non-breast malignancy (3 vs. 6), despite increases seen in central nervous system events (21 vs. 15 of observation arm) and death as first event (6 vs. 3).

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BCIRG 006 Shows Trastuzumab (Herceptin) Improves Disease-free Survival and Overall Survival Over for HER2-positive Early Breast Cancer: Presented at IBCEF [Doctor's Guide]
VIENNA, AUSTRIA — February 20, 2006 — Adjuvant trastuzumab (Herceptin(R)) 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 11th 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 three-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 three 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 three 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 non-haematological toxicity, most were seen in 2% to 6% of patients, except for irregular menses (20%).

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Interim Combined Analysis Shows Benefits of Adjuvant trastuzumab (Herceptin) in HER2-positive Early Breast Cancer: Presented at IBCEF [Doctor's Guide]
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/m2 3 times weekly for 4 cycles; AC) followed by paclitaxel (P) with or without concurrent trastuzumab.

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

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