GlaxoSmithKline 's new breast cancer drug Tykerb is to go head-to-head in a major set of trials with Roche/Genentech's blockbuster Herceptin.

The US National Cancer Institute says that 8,000 patients in 50 countries will be given either Herceptin (trastuzumab) or Tykerb (lapatinib), or Herceptin followed by Tykerb, or the two drugs in combination. The trial, called ALTTO, has been developed by The Breast Cancer Intergroup of North America and the Breast International Group in Brussels, Belgium and is due to continue until 2011.

The NCI said that the study is designed “to answer the most pressing questions regarding use of two widely used cancer agents: whether one agent is more effective, which agent is safer for patients and what benefit will be derived by taking the drugs separately, in tandem order, or together”? Both Herceptin and Tykerb have been approved for treating HER2-positive breast cancer, which affects up to 25% of breast cancer patients.

ALTTO will be the first head-to-head comparison of trastuzumab and lapatinib in the earliest, most treatable stages of cancer. It is unusual in that it has two different designs depending on whether patients with stage I or stage II breast cancer have already been treated with chemotherapy. As such, it will compare four different regimens of targeted therapy administered over a 52-week period.

Edith Perez of the Mayo Clinic in Florida, who is leading the study for TBCI, said “it may be that using two treatments that work in different ways against HER2-positive breast cancer offers a complementary strategy that is more powerful than either drug alone". Martine Piccart, of the Université Libre de Bruxelles and lead investigator for BIG, added that the difference between this study “and many that came before it is that the collection of biological materials occurs as the trial is being conducted, not as an afterthought. While there are exceptions, not many companies or organisations have been willing to invest in that kind of research before".

She concluded by noting that "now we have the chance to optimise therapy with powerful drugs in order to provide the best treatment possible for each of our patients”.

Setback in battle to beat malaria
Meantime, GSK noted that it has halted the development of one malaria treatment and recalled another after studies showed that the drugs lowered haemoglobin levels which can lead to anaemia.

GSK and partner Medicines for Malaria Venture said that they recently received disappointing data from two Phase III trials assessing the use of the combination therapy Dacart, a fixed-dose combination of artesunate and Lapdap (chlorproguanil and dapsone). The first trial was primarily designed to establish the efficacy of Dacart versus Novartis’ Coartem (artemether–lumefantrine), the gold standard malaria treatment.

The study, in 1,372 patients, showed statistical non-inferiority with 94% efficacy at 28 days for Dacart and 97% for Coartem. However, the reduction in haemoglobin concentration observed in patients with glucose-6-phosphate dehydrogenase deficiency (a hereditary enzyme disorder that affects 10%-25% of the population in sub-Saharan Africa) taking Dacart was greater than that of Coartem. The second 892-patient trial revealed significant reductions in haemoglobin levels of patients with G6PD deficiency for both Dacart and Lapdap.

As a result, further development of Dacart has been terminated and GSK is recalling Lapdap in Kenya, only market with recent sales of the product. Lynn Marks, senior vice president of the firm’s Medicines Development Centre for Infectious Diseases, said the news “is disappointing and highlights the high-risk, complex nature of pharmaceutical R&D”. However, she added that GSK remains committed to working with partners such as MMV “to seek solutions for patients suffering from this devastating disease”.