Date: 2014-06-01
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 50th American Society of Clinical Oncology (ASCO) Annual Meeting, May 30 to June 3, 2014, in Chicago
Company: GSK (UK)
Product: lapatinib (Tykerb™/Tyverb™) and trastuzumab
Action
mechanism: Lapatinib is an orally active, reversible, small molecule tyrosine kinase inhibitor that potently inhibits both ErbB1 and ErbB2 tyrosine kinase activity.
Disease: HER2 positive early breast cancer
Therapeutic area: Cancer - Oncology
Country:
Trial
details: ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation trial; ) 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. (NCT00490139)
Latest
news: * On June 1, 2014, GSK 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 at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois. 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%).
