ASCO 2012 – a new treatment for HER2-positive breast cancer?

Results from a trial of T-DM1 are encouraging

In this second report from the ASCO conference, Nell Barrie discusses an experimental “armed antibody” for the treatment of breast cancer.

While patriotic Britons sheltered under their umbrellas over the rainy Jubilee weekend, the ASCO cancer conference in Chicago brought news of encouraging results from a trial of a new treatment for women with HER2-positive breast cancers. The new drug, T-DM1, appears not only to be better than the standard treatment, but kinder for patients as well.

The largest hall at the conference was packed with researchers keen to hear the news, and delegates overflowed into another barn-like room to watch the session via video link.

Dr Kimberly Blackwell of Duke Cancer Institute introduced the results of the international EMILIA trial, telling the huge audience that she was honoured to present the trial on behalf of her collaborators from around the world, and began by explaining what makes this new treatment special.

About 20 to 25 per cent of breast cancers have a protein called HER2 on the surface of the cancer cells. We can already target these cells using the well-known drug Herceptin (trastuzumab). Herceptin is an antibody drug – a molecule that binds to the HER2 protein to help block signals that encourage the cancer cells to grow.

Double whammy

T-DM1 takes this targeted approach to the next level. The treatment is an ‘antibody-drug conjugate’ – a combination of the Herceptin antibody linked to a chemotherapy drug, forming a single potent package. This double whammy means T-DM1 can seek out the cancer cells (thanks to the antibody) and then deliver a toxic dose of chemotherapy exactly where it’s needed.

That’s the theory – but does it work in practice? The EMILIA trial compared two groups of women with HER2-positive breast cancer that had spread – all the women had already been treated with Herceptin and a taxane drug. One group received the new drug, T-DM1, while the other were given a standard treatment for this type of breast cancer – two drugs called lapatinib and capecitabine.

The results presented to the conference were very encouraging. The researchers compared how long it took for disease to get worse in the two groups of women – a measure of how well the different treatments were working. Women receiving T-DM1 survived for 3 months longer before their cancers progressed – a big difference for patients with advanced cancer.

On top of this, the researchers didn’t find a ‘maximum tolerated dose’ of the drug – meaning that even at the highest dose tested, side effects were fairly minimal.

Unanswered question

But the key unanswered question is whether T-DM1 can help women survive for longer overall. Many of the women taking T-DM1 are still alive, so we can’t yet tell exactly how long the average survival time is. But the results so far are encouraging – 12 and 24 months after receiving the treatment, the women on T-DM1 appeared to be doing better than those in the comparison group.

How big a step is this in the treatment of breast cancer? After the results had been presented, Dr Louis Weiner from the Georgetown Lombardi Comprehensive Cancer Center stepped up to put the research into context. He explained that researchers expect T-DM1 to be approved shortly by the US Food and Drug Administration for treating HER2-positive breast cancer that has spread – a crucial regulatory hurdle.

Dr Weiner also gave a nod to the fascinating scientific concepts behind the new treatment, harking back to one of the first researchers to grasp the potential of targeted treatments. One hundred years ago, German scientist Paul Ehrlich had imagined a way to treat diseases using ‘magic bullets’ that could directly target harmful microbes inside the body while leaving healthy tissues unharmed. The EMILIA results are not a complete realisation of Ehrlich’s dream – as T-DM1 was not without side effects – but they do at least represent concrete progress towards drugs that specifically home-in on cancer cells.

What’s next?

So what happens now? Most importantly, we still need the overall survival results to show if T-DM1 helps women survive for longer than existing standard treatment – the signs are encouraging, but confirmation is crucial and nothing is certain in medical research. These are interim results and the final story won’t be known for a couple more years.

Researchers are also keen to test this new drug in combination with other treatments, and to see if it could help women with earlier stage breast cancer. Trials are already under way.

But it’s not just breast cancer patients who could benefit from these new antibody-drug combinations. A further session the day after these key results were announced outlined research using a similar approach to treat Hodgkin’s lymphoma. In this case, the drug – Adcetris – has already been approved for use – showing how quickly this field is growing.

As one speaker put it, “this is a paradigm shift in the way we treat our patients… it holds great promise for the future.”