GSK announces Phase III ALTTO results for anti-HER2 therapy combination in the adjuvant breast cancer treatment setting

Issued: London UK

GlaxoSmithKline plc (LSE: GSK) today announced that the Phase III study of two anti-HER2 agents, lapatinib (Tykerb™/Tyverb™) and trastuzumab, did not meet the primary endpoint of improved disease free survival (DFS) compared to single agent therapy with trastuzumab as adjuvant treatment for HER2 positive early breast cancer. The safety profile was consistent with the established safety profile of the study drugs, with no new safety signals observed.

These results were presented today at the 50^th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

“While it is disappointing that ALTTO did not meet its primary endpoint, we now have a tremendous amount of information that will help to further our knowledge of the biology of this disease and inform future studies in HER2 positive breast cancer in the adjuvant setting. Further analysis of these data will continue over the coming months,” said Dr. Rafael Amado, Senior Vice President Oncology R&D at GSK.  “We are most grateful to the more than 8,000 patients across the world who participated in ALTTO—their generous contribution to the scientific community will facilitate a greater understanding of this aggressive disease.”

The primary analysis of the study tested for superiority (p≤0.025) between the combination arm and trastuzumab alone with respect to DFS; the trastuzumab followed by lapatinib arm was tested for non-inferiority (p≤0.025). The results showed that at four years, 88 percent of women lived without their disease returning (4-year DFS) in the lapatinib plus trastuzumab arm and 86 percent in the trastuzumab arm [HR 0.84 (97.5% CI, 0.70-1.02; p=0.048)]. The 4-year DFS rate for the trastuzumab followed by lapatinib arm was 87 percent compared to 86 percent in the trastuzumab arm [HR 0.96 (97.5% CI, 0.80-1.15; p=0.061)].

Adverse events (AEs) more frequently reported in the lapatinib plus trastuzumab arm compared to the trastuzumab arm were diarrhoea (75% vs. 20%), rash (55% vs. 20%) and hepatobiliary (23% vs. 16%). Diarrhoea, grade 3 or higher, was increased in all lapatinib containing treatment arms (5-15%), compared to trastuzumab alone (1%). The incidence of febrile neutropenia was <1% across treatment arms and primary cardiac endpoints were <1% in all arms. Overall, fatal AEs were consistent between treatment groups (<1%), with no clear pattern to the reported events. AEs leading to discontinuation were higher in the lapatinib containing arms (23% in the combination arm) compared with the trastuzumab arm (8%).

About ALTTO

ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation trial; NCT00490139) is a randomised, multi-centre, open-label, Phase III study of adjuvant lapatinib, trastuzumab, their sequence and their combination in patients with HER2 positive primary breast cancer. Randomised patients received anti-HER2 therapy (lapatinib, trastuzumab) after completing all chemotherapy, concurrent with a taxane following anthracycline, or concurrent with a non-anthracycline, platinum-containing regimen.

ALTTO randomised 8,381 patients at nearly 1,000 research sites in 44 countries. Patient enrolment began in June 2007 and was completed in July 2011.  The lapatinib arm was discontinued in 2011, after an independent review committee determined that the lapatinib alone arm was unlikely to meet the pre-specified criteria to demonstrate non-inferiority to trastuzumab alone with respect to disease-free survival.

ALTTO is led by two prominent academic groups—BIG (Breast International Group) and NCCTG (North Central Cancer Treatment Group)—in collaboration with GlaxoSmithKline. Please visit http://www.alttotrials.com for additional information on this trial.

About lapatinib

Lapatinib— an orally active, reversible, small molecule TKI that potently inhibits both ErbB1 and ErbB2 tyrosine kinase activity—is marketed as Tykerb^™ in the U.S. and as Tyverb^™ in Europe and other countries across the world. Lapatinib is not approved or licensed anywhere in the world for the treatment of HER2 positive early breast cancer.

For full US Prescribing Information for Tykerb™ (lapatinib), including Boxed Warning for hepatotoxicity, please visit: https://www.gsksource.com/gskprm/htdocs/documents/TYKERB-PI-PIL.PDF. For the European Union (EU) Summary of Product Characteristics (SPC) for Tyverb™ (lapatinib) in approved indications, please visit http://health.gsk.com/.  

Tykerb^™ and Tyverb^™ are trademarks of the GSK group of companies.

GSK – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer.  For further information please visit www.gsk.com.

Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D 'Risk factors' in the company's Annual Report on Form 20-F for 2013.