GSK Starts Tykerb-Herceptin Head-to-Head Phase III Trial in Early Breast Cancer

U.K. pharmaceutical company GlaxoSmithKline (GSK) has announced the initiation of the Neo-ALTO Phase III clinical trial that will evaluate the benefits of oncology treatment Tykerb/Tyverb (lapatinib) as a first line treatment in HER-2 positive breast cancer. The studies will be conducted in collaboration with the Breast International Group (BIG) and the Spanish Breast Cancer Cooperative Group (SOLTI). Tykerb is currently approved in the United States and recommended for approval in Europe for use in Her-2 positive advanced or metastatic breast cancer patients who have previously been treated for their conditions with anthracyclines, taxanes, or trastuzumab (Herceptin, Genentech; Roche, U.S./Switzerland; see United Kingdom: 25 April 2008: GSK Makes Progress on European Marketing Authorisation for Breast Cancer Drug Tyverb)

The three-arm, randomised, open-label trial will be conducted in 450 patients in 26 countries. Prior to surgery, HER2 positive breast cancer patients will receive Tykerb, Herceptin or a combination of both over six weeks. Chemotherapy agent paclitaxel (Taxol, Bristol Myers-Squibb, U.S.) will be then added to each arm of the trial for 12 weeks, after which point, patients will undergo surgery. Upon surgery, patients will receive three courses of chemotherapy, which will be followed by 34 weeks of treatment with the initial mono or combination therapy. The primary endpoint of the trial is to assess and compare the rate of complete cancer-cell eradication for all arms of the study at the time of surgery. Secondary endpoints will evaluate Tykerb's safety profile, tumour response rate as well as cancer-free and overall survival rates.

The study is part of GSK's programme to compare the benefits of its drug to that of rival drug and market leader Herceptin. Last year, GSK compared the effects of the two drugs when administered after surgery. Tykerb is the first once-daily oral dual tyrosine kinase inhibitor. Indeed, Tykerb inhibits both the ErbB1 (EGFR) and ErbB2 (HER2/neu) receptors, both involved in cell proliferation, as opposed to Herceptin, which is an injectable HER2 inhibitor. HER2-positive patients are believed to account for around 25% of all breast cancer cases.

Outlook and Implications

GSK has finally initiated the long-awaited head-to-head comparison between its drug and market leader Herceptin. The trials had been on the cards for over a year and if anything come slightly behind schedule. If Tykerb comes out on top in the study, it will support GSK's push to get the drug approved as a first-line treatment and challenge Herceptin's market dominance. The stakes are high for GSK as Herceptin, a drug licensed solely for the treatment of breast cancer, generated first-quarter sales of 1.22 billion Swiss francs (US$1.17 billion) in the first quarter of 2008, while Tykerb brought in £19 million (US$37.13 million) in revenues. The drug has the added convenience of being a once-daily oral treatment compared to Herceptin, which necessitates weekly or three-weekly injections of 30-90 minutes. Although Tykerb has a long way to go before being as profitable as its rival, it is estimated that peak sales could reach an annual US$1.35 billion by 2010 in the breast cancer indication alone. Tykerb also has potential to treat other solid tumour cancers, such as lung cancer, which is expected to boost the drug's peak sales to an annual US$4 billion.