GlaxoSmithKline has decided to revise the format of its Phase III trial of Tykerb in HER2-positive early-stage breast cancer, after it emerged that use of the drug on its own was unlikely to be as effective as treatment with the comparator drug.
An interim review of the ALTTO study showed that Tykerb/Tyverb (lapatinib) as a monotherapy would be unlikely to show non-inferiority to treatment with Roche's Herceptin (trastuzumab) in extending disease-free survival these patients.
In addition to Herceptin and Tykerb arms, the trial is also looking at the two drugs in combination and given sequentially, and will continue to follow-up patients on these regimens, said GSK.
"Patients assigned to the lapatinib alone arm of the trial will discontinue lapatinib and discuss treatment options with their study physician," said the company in a statement.
The announcement is a blow to GSK as extension of Tykerb's indications into the early-stage setting will be an important factor in accelerating sales uptake.
GSK's drug is already approved in most countries around the world as a treatment for advanced, metastatic HER2-positive breast cancer, and brought in £111 million in the first six months of 2011, up 3%, with sales declining 17% in the USA.
ALTTO got underway in 2007 and completed patient enrolment earlier this year. It was designed to support the use of Tykerb in the adjuvant setting, in other words treatment given after primary treatment of the breast cancer and surgery.
Previous trials have already shown that the combination of Tykerb and Herceptin is superior to either drug used alone in terms of tumour response rates. While ALTTO may reinforce those findings and open up adjuvant use in combination with Roche's drug, it has failed to position Tykerb as an alternative to Herceptin in the adjuvant setting.