Lapatinib (Tykerb/Tyverb) to be investigated in landmark early breast cancer trial

GlaxoSmithKline (GSK), in collaboration with the Breast International Group (BIG), a leading academic breast cancer research network, and one of its member groups, the Spanish Breast Cancer Cooperative Group (SOLTI), today announced the start of a global Phase III study that will examine the role of lapatinib (Tykerb®/Tyverb®)in the treatment of early breast cancer (EBC). Neo-ALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) will evaluate and compare the rate at which cancer cells disappear in the breast following treatment with lapatinib and/or trastuzumab before surgery in women with early-stage ErbB2-positive (HER2-positive) positive breast cancer. This type of treatment is referred to as neo-adjuvant therapy. Lapatinib is an investigational drug and has not yet been approved for this indication.

“The evolution seen in breast cancer care has been tremendous in the last few last decades,” said Dr. José Baselga, Co-Chair on Neo-ALTTO and Scientific Chair of the SOLTI Group, Spain. “Surgery, in the form of a radical mastectomy of the breast, was traditionally the first line treatment offered to patients with little or no improvement in overall survival. Now we have a range of sophisticated targeted treatments that can significantly delay disease progression and increase survival. Through trials such as Neo-ALTTO, oncologists may be better able to optimise the use of these agents.”

One in four women diagnosed with early breast cancer have tumours that are ErbB2-positive.[1] It is well recognised that these women have a higher risk of their cancer returning – either at the location of the original tumour (local recurrence), or when the cancer spreads to other organs (distant recurrence) – even after receiving additional therapies.1

“The launch of Neo-ALTTO is extremely exciting, as this study will help physicians answer important clinical questions relating to the neoadjuvant treatment regimen of ErbB2-positive breast cancer,” said Dr. Martine Piccart, investigator on Neo-ALTTO and Chairperson of the Breast International Group, Institute Jules Bordet, Brussels. “All too often clinicians and patients face the problem of disease recurrence, and women with high levels of ErbB2 protein are at a greater risk of this occurring. It is vital that early stage breast cancer is treated effectively from the outset with the right combination or sequence of therapies.”

Neo-ALTTO is a three-arm, randomised, multi-centre, open-label Phase III study of neoadjuvant lapatinib, neoadjuvant trastuzumab, and a combination of neoadjuvant lapatinib and trastuzumab in women with ErbB2-positive primary breast cancer. After treatment for six weeks, the same targeted therapy will be repeated for 12 weeks with the addition of paclitaxel. Surgery will be performed on all patients, after which each patient will receive three courses of chemotherapy followed by the same targeted therapy for 34 weeks. The primary objective of Neo-ALTTO is to evaluate and compare the rate of pathological complete response (or complete eradication of the tumour) at the time of surgery, as well as understand the biological difference of the three treatment regimens using a neoadjuvant approach. Secondary objectives include measurements of safety and tolerability, tumour response rate, disease-free survival and overall survival. Target enrolment is 450 patients with 130 clinical trial centres planned across 26 different countries.

It is hoped that Neo-ALTTO will lead to the discovery of new molecular biomarkers that help to better identify the benefits of lapatinib or trastuzumab.

“GSK is proud to collaborate with such esteemed research groups as BIG and SOLTI for the study of lapatinib in this early breast cancer setting,” said Paolo Paoletti, MD, Senior Vice President, Oncology Medicines Development Centre of GSK. “This important global Phase III study, which has begun enrolling within a year of the FDA approval of lapatinib, demonstrates the confidence that the oncology community has in lapatinib and the importance of identifying the most effective treatment regimen for patients with early stage ErbB2-positive breast cancer.”

Worldwide, breast cancer is by far the most frequent cancer affecting women, with over one million new cases each year, and the leading cause of female cancer-related deaths.[2] Approximately 20 to 85 percent of patients (depending on initial stage, tumour biology, and treatment strategy) diagnosed with early breast cancer will develop recurrent and/or metastatic disease.[3]