Extending Adjuvant Trastuzumab Treatment Time Provided No Additional Benefit

This abstract will be presented at a press conference hosted by C. Kent Osborne, M.D., director of the Lester and Sue Smith Breast Cancer Center at Baylor College of Medicine, on Friday, Dec. 7 at 7:30 a.m. CT in Room 217 A-C of the Henry B. Gonzales Convention Center. Reporters who cannot attend in person can call in using the following information:• U.S./Canada (toll free): 1 (800) 446-2782• International (toll call): 1 (847) 413-3235

Newswise — SAN ANTONIO — One year of adjuvant trastuzumab should remain the standard of care for patients with HER2-postive early-stage breast cancer, according to data from the phase III HERA trial, which compared the efficacy and safety of one year and two years of treatment.

“Giving trastuzumab for a longer duration (two years) did not improve disease-free or overall survival compared with one year of trastuzumab treatment,” said Martine J. Piccart, M.D., Ph.D., chief of the medicine department at the Jules Bordet Institute in Brussels, Belgium, president of the European Society for Medical Oncology and chair of the Breast International Group (BIG). Piccart presented these data at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8.

Piccart and colleagues took part in the HERA trial, an international, multicenter, phase III, randomized trial run by BIG and Roche that spanned several countries. They followed 5,102 women with HER2-positive early-stage breast cancer randomly assigned to trastuzumab every three weeks for one year or two years, or to observation. All women completed primary therapy of surgery, chemotherapy and radiotherapy as indicated.

Disease-free status and overall survival rates were comparable between the one- and two-year trastuzumab arms. In addition, while the primary cardiac endpoint of symptomatic congestive heart failure was comparable in both arms, the secondary cardiac endpoint of asymptomatic cardiac dysfunction was higher in the two-year arm, at 7.2 percent compared with 4.1 percent in the one-year arm. Most of the cardiac events occurred during trastuzumab administration, and the majority were reversible when the trastuzumab was stopped.

“The HERA trial showed the sustainability of the efficacy of trastuzumab, proving that a significant proportion of patients treated with trastuzumab in the adjuvant setting are alive and free of disease recurrence after a median follow-up of eight years,” Piccart said. “It is also reassuring with regard to the low cardiac toxicity of trastuzumab when given after adjuvant chemotherapy. Finally, it confirms that one year of adjuvant trastuzuamb should remain the standard of care in women with HER2-positive early breast cancer.”

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The mission of the 2012 CTRC-AACR San Antonio Breast Cancer Symposium is to produce a unique and comprehensive scientific meeting that encompasses the full spectrum of breast cancer research, facilitating the rapid translation of new knowledge into better care for patients with breast cancer. The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio, the American Association for Cancer Research (AACR) and Baylor College of Medicine are joint sponsors of the San Antonio Breast Cancer Symposium. This collaboration utilizes the clinical strengths of the CTRC and Baylor and the AACR’s scientific prestige in basic, translational and clinical cancer research to expedite the delivery of the latest scientific advances to the clinic. For more information about the symposium, please visit www.sabcs.org.

Abstract:Publication Number: S5-2

Title: HERA TRIAL: 2 years versus 1 year of trastuzumab after adjuvant chemotherapy in women with HER2-positive early breast cancer at 8 years of median follow up

Martine J Piccart-Gebhart2, Aron Goldhirsch1, Marion Procter3, Evandro de Azambuja4, Harald A Weber5, Michael Untch6, Ian Smith7, Luca Gianni8, Christian Jackisch9, David Cameron10, Richard Bell11, Mitch Dowsett12, Richard D Gelber13, BrianLeyland-Jones14, José Baselga15 and On Behalf of the HERA Study Team16. 1Department of Medicine, European Institute of Oncology, Milan, Italy; 2Department of Medicine, BrEAST Data Centre, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium; 3Frontier Science (Scotland) Ltd, Kincraig, Kingussie, United Kingdom; 4Medical Oncology Clinic, BrEAST Data Centre, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium; 5F. Hoffmann-La Roche, Basel, Switzerland; 6Helios Klinikum Berlin-Buch, Akademisches LK der Universität Charité, Berlin, Germany; 7Breast Unit, Royal Marsden Hospital and Institute of Cancer Research, London, United Kingdom; 8Department of Medical Oncology, San Raffaele Institute, Milan, Italy; 9Department of Gynecology and Obstetrics, Klinikum Offenbach, Offenbach, Germany; 10Department of Oncology, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom; 11Andrew Love Cancer Centre, Geelong Hospital, Geelong, Australia; 12Academic Department of Biochemistry, The Royal Marsden NHS Trust, London, United Kingdom; 13Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA; 14Sanford Research, Sioux Falls, SD; 15Division of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Boston, MA and 16.

Body: Background: One year (yr) of trastuzumab (T) significantly improves disease-free (DFS) and overall survival (OS) in patients with HER2-positive early breast cancer (EBC) and is considered the standard of care. HERA is the only randomized trial investigating whether longer duration of T can further improve efficacy outcome.

Materials and Methods: HERA (BIG 01-01) is an international, multicenter, phase III randomized trial involving 5102 women with HER2-positive EBC. Pts were randomized, after completion of primary therapy [surgery, chemotherapy and radiotherapy as indicated], to T every 3 weeks for 1 yr, 2 years (yrs), or observation. This landmark efficacy analysis compares the outcome of pts randomized to either 2 yrs or 1 yr of T who were disease-free at 1 yr after randomization (N=1553 for 2 yrs, and N=1552 for 1 yr). The primary endpoint is DFS and secondary endpoints are OS and time to distant recurrence (TTDR). Updated efficacy analyses of the T arms vs. observation at 8-yrs of median follow-up (FU) are also presented.

Results: On 12 April 2012 HERA reached the target number of 725 DFS events needed for 80% power to detect a true hazard ratio (HR) of 0.80 for the comparison of 2 yrs vs. 1 yr of T. The unadjusted HR for an event in the 2-yr vs. 1-yr T arms was 0.99 (95% CI 0.85-1.14; P=0.86). OS in the two arms was comparable [HR=1.05 (95% CI 0.86-1.28; P=0.63)]. TTDR results were similar. The primary cardiac endpoint* was comparable (1.0% vs. 0.8% for 2-yr and 1-yr arms, respectively), but the secondary cardiac endpoint** was higher in the 2-yr arm (7.2% vs. 4.1%). Importantly, the durable benefit in DFS and OS for both 1 yr and 2 yrs of T compared with observation remains stable at 8 yrs of median FU. Subgroup analyses including by hormone receptor status will be available for the meeting.

Conclusions: These results confirm that 1 yr of adjuvant T remains the standard of care for HER2-positive EBC pts. It is also reassuring that the significant improvement in DFS and OS persists over time and that the incidence of cardiac endpoints remains low at a median FU of 8 yrs.

* NYHA class III or IV, confirmed by a cardiologist, and LVEF < 50% and 10% below baseline, OR cardiac death.** LVEF < 50% and 10% below baseline confirmed by repeat assessment, excluding patients with a primary cardiac endpoint.