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PUBLIC RELEASE DATE:
11-Dec-2013

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Contact: Jeremy Moore
jeremy.moore@aacr.org
215-446-7109
American Association for Cancer Research

Researchers to present event-free and overall survival results from NeoALTTO trial

SAN ANTONIO — Results from the initial analysis of event-free and overall survival for patients enrolled in the randomized, phase III Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO) trial are to be presented here at the 2013 San Antonio Breast Cancer Symposium, held Dec. 10–14.

"NeoALTTO is a randomized, phase III clinical trial evaluating whether a combination of two HER2-targeted therapies, trastuzumab and lapatinib, given with standard paclitaxel chemotherapy before surgery [neoadjuvant therapy] is better than just one of the HER2-targeted therapies given with the same chemotherapy," said Martine Piccart-Gebhart, M.D., Ph.D., chair of the Breast International Group (BIG) in Brussels, Belgium. "We previously reported that the combination therapy resulted in more patients having a pathologic complete response.

"In San Antonio, we will present our analysis of whether improved pathologic complete response rates translate into better long-term outcomes for patients," continued Piccart-Gebhart. "I believe that our results will be vital for the process of drug development in the field of early HER2-positive breast cancer."

Neoadjuvant therapy is treatment given to shrink or eliminate a tumor before surgery. In some patients with breast cancer, neoadjuvant therapy effectively eliminates the tumor, and no invasive cancer is detectable in breast tissue and lymph nodes removed during surgery. These patients are said to have had a pathologic complete response.

In 2014, the results of NeoALTTO's "sister" trial, Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO), which is testing the effectiveness of dual treatment with trastuzumab and lapatinib after breast cancer surgery, will also become available, according to Piccart-Gebhart. "If the results of both studies are in line with each other, and depending on the strength of the results, we could witness a new standard of care for managing primary HER2-positive breast cancer," she said.

From January 2008 to May 2010, Piccart-Gebhart and colleagues enrolled in the NeoALTTO study 455 patients with HER2-positive primary breast cancer with tumors greater than 2 cm in diameter. Of those patients, 154 were randomly assigned to lapatinib, 149 to trastuzumab, and 152 to the combination. These HER2-targeted therapies were given alone for six weeks and then the chemotherapy paclitaxel was also administered for a further 12 weeks, at which point surgery was conducted. After surgery, patients received adjuvant chemotherapy followed by the same HER2-targeted therapy as in the neoadjuvant phase to complete 52 weeks. Follow-up is planned for 10 years after the last patient was randomized.

The researchers have previously reported that 51.3 percent of patients randomly assigned to neoadjuvant trastuzumab plus lapatinib had a pathologic complete response compared with 29.5 percent and 24.7 percent of patients randomly assigned to neoadjuvant trastuzumab and neoadjuvant lapatinib, respectively.

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This study was supported by funds from GlaxoSmithKline PLC. Piccart-Gebhart has received honoraria from Roche, and her institution has received research funding from GlaxoSmithKline PLC.

This study was managed under the Breast International Group umbrella with two of its member groups, the BrEAST Data Centre and the SOLTI academic research group. Overall, 455 patients entered in the study from 86 sites in 23 countries in Europe, Asia, North and South America, and South Africa.

This research will be presented at the 2013 San Antonio Breast Cancer Symposium Wednesday, Dec. 11, 7:30 a.m. CT, during a press conference hosted by Jennifer Litton, M.D., associate professor, Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center. Press conferences will be held in Room 217D of the Henry B. Gonzalez Convention Center, San Antonio, Texas.

Reporters who cannot attend in person can call into the press conferences using the following information:

To interview Martine Piccart-Gebhart, contact Jeremy Moore at jeremy.moore@aacr.org or 215-446-7109.

The mission of the 2013 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 http://www.sabcs.org.

Publication Number: S1-01

Presenter: Martine Piccart-Gebhart, M.D., Ph.D.

Title: The association between event-free survival and pathological complete response to neoadjuvant lapatinib, trastuzumab or their combination in HER2-positive breast cancer. Survival follow-up analysis of the NeoALTTO study (BIG 1-06)

Authors: Martine Piccart-Gebhart1, Andrew P Holmes2, Evandro de Azambuja3, Serena Di Cosimo4, Ramona Swaby5, Michael Untch6, Christian Jackisch7, Istvan Lang8, Ian Smith9, Frances Boyle10, Binghe Xu11, Carlos Barrios12, Richard Gelber13, Holger Eidtmann14 and José Baselga15. 1Jules Bordet Institute, Brussels, Belgium; 2Frontier Science (Scotland) Ltd, Kincraig, Kingussie, United Kingdom; 3Jules Bordet Institute, Brussels, Belgium; 4Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 5GlaxoSmithKline; 6Academic Hospital of the University Charite, Germany; 7Klinikum Offenbach, Germany; 8National Institute of Oncology, Hungary; 9Royal Marsden Hospital and Institute of Cancer Research, London, United Arab Emirates; 10Patricia Ritchie Centre for Cancer Care and Research, Mater Hospital North Sydney and University of Sydney, Australia; 11Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China; 12PUCRS School of Medicine, Porto Alegre, Belgium; 13Dana-Farber Cancer Institute, Boston; 14University Hospital Kiel, Kiel, Germany and 15Memorial Sloan Kettering Cancer Center, New York.

Background: The NeoALTTO study demonstrated a significantly higher breast pathological complete response (pCR) rate (NSABP definition – ypT0/is) with dual HER2 blockade using lapatinib and trastuzumab compared with single HER2 blockade using either lapatinib or trastuzumab (51.3% vs. 24.7% vs. 29.5%, respectively; p< 0.01 for both) in HER2 positive primary breast cancer (BC). A similar pattern was seen for locoregional pCR (ypT0/is ypN0) (Baselga J et al. Lancet 2012).

Material and Methods: From January, 2008, to December, 2009, 455 patients were randomized from 99 participating sites in 23 countries. Patients were randomized to receive either lapatinib 1500 mg/d (154 pts), or trastuzumab 4 mg/kg IV loading dose followed by 2 mg/kg IV weekly (149 pts), or lapatinib 1000 mg/d with trastuzumab for a total of 6 weeks (152 pts). After this biological window, patients continued on the same targeted therapy plus weekly paclitaxel 80 mg/m˛ for a further 12 weeks, until definitive surgery (total neoadjuvant therapy duration of 18 weeks). After surgery, patients received 3 cycles of adjuvant FEC followed by the same targeted therapy as in the biological window of the neoadjuvant phase for a further 34 weeks (to complete 52 weeks of anti-HER2 therapy), with on-going follow-up planned until 10 years after last randomised patient. Secondary objectives included disease-free survival and overall survival (OS). Following current practice and draft FDA recommendations for neoadjuvant trial endpoints, an amendment was made to the protocol secondary objectives (released in May 2013). DFS (from surgery) was replaced by event-free survival (EFS) from randomisation; OS from surgery was correspondingly replaced with OS from randomisation, and examination of the association between these survival endpoints and locoregional pCR (ypT0/is ypN0) was added as a secondary objective. EFS was defined as the time from randomization to first EFS event (breast cancer relapse, second primary malignancy or death without recurrence). OS was defined as the time from randomization to death from any cause.

Results: The clinical cut-off date for the first planned analysis of these secondary objectives was on 26 May 2013, three years after the date of last surgery. Data cleaning is ongoing and analysis will be completed by November 2013. Results for EFS, OS and their association with pCR will be presented at the meeting.

Funding: GlaxoSmithKline is the sponsor of this trial.



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