Super Herceptin?


So how does T-DM1, an investigational agent that attaches Herceptin to a toxic drug, stand up when tested against the current treatment for cancer already progressing on Herceptin?Well, it's been quite a busy time at ASCO, a lot of advancements on many fronts. The first and foremost is a new HER2-targeted therapy called T-DM1. This is for patients with HER2-positive breast cancer. We've known for many years that the antibody Herceptin can clearly improve outcome in early stage and can even improve survival in advanced stage. However, in advanced breast cancer, most patients eventually progress. In addition to Herceptin, there has been one other FDA approval, a drug called Tykerb, or lapatinib. When combined with a chemotherapy called Xeloda, it can delay progression, but it hasn't shown to improve survival. So, we're still in need of better therapies for HER2-positive advanced breast cancer.This new drug, T-DM1, uses the Herceptin antibody, but it's bound to a very toxic drug. This drug couldn't ordinarily be used alone because it has too many side effects, but when it's bound to the Herceptin antibody with a linker, it works like a Trojan horse. It gets internalized into the tumor cell and induces cell death.This drug was earlier found to be effective in patients who had already progressed on Herceptin and Tykerb, but the FDA did not want to use this data alone to approve the drug. The FDA wanted to see a randomized trial, and then it wanted to see a survival advantage. So, it took another two years to get the trial done. The researchers compared T-DM1 to Tykerb and Xeloda, and the results of this trial show a pretty dramatic benefit. There was about a third longer time to progression in patients receiving T-DM1 compared with Tykerb and Xeloda. There also seems to be a survival benefit, but it's too early to fully confirm it. However, the way the data is panning out, it almost will certainly show a survival advantage. Most of us think this will be sufficient to get the drug approved, but we'll have to see if that's the case. It will certainly change the treatment approaches in treatment of HER2-positive breast cancer.There are also combinations with T-DM1 being tested. We've mostly heard about safety data, not effectiveness just yet. We know we can combine it with the chemotherapy Taxol, and it appears to be safe. There is a large randomized trial combining T-DM1 with another drug called pertuzumab. This is an antibody, when combined with Herceptin, appears to improve outcomes in first-line therapy, whereas T-DM1 was tested in second-line therapy.Finally, as one might expect, there are trials designed to look at T-DM1 in early-stage breast cancer. We know the best we can do for patients is to prevent metastatic recurrence in the first place, so we're putting a lot of effort into treating early-stage breast cancer. No results yet, though; it will probably take a couple of years for that data to emerge. When you look at the big picture, you have to recognize that HER2-positive breast cancer 20 years ago was considered the most aggressive type of breast cancer. Now it's one of the better types of breast cancer because we have effective therapies for it. But there is still a lot of room for improvement. We're still not curing advanced HER2-positive breast cancer.

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