ASCO 2015

Comment: Eribulin extends overall survival for advanced liposarcoma and leiomyosarcoma

Prof Gary Schwartz - Columbia University, New York, USA

What are the challenges of sarcoma? What were the investigators trying to do?

Sarcoma is a rare cancer. When we usually speak about cancer we talk about carcinomas which are organ cancers, sarcomas are the connected tissue cancers. In the United States we’ll see about 14,000 connective tissue cancers a year, making it really an orphan disease. The complexity of sarcoma, in fact, is that there are fifty different subtypes of sarcoma. You can imagine every soft tissue element in the body can develop into a cancer, believe it or not. The ones that are focussed in this particular abstract that will be presented today at ASCO are two subtypes of sarcoma, one is leiomyosarcoma, which are cancers of the muscle, and the other is called adipocyte tumours and that has to be a little bit clarified. We also call these liposarcomas, which are cancers of the fat and actually people were very surprised that fat can become malignant and, yes, you can get malignancies of the fat called liposarcomas, of which in fact there are several types of those as well. So that’s the complexity of the sarcoma field. To be a sarcoma doctor, in fact, you have to know just not one cancer, sarcoma, you have to know about fifty different cancers to be a sarcoma specialist.

What is your take on what was discovered in the study?

So it was a randomised clinical trial of this drug called eribulin by Eisai Pharmaceuticals which targets, they say, the microtubule that’s part of what we call the spindle of the dividing cancer cell. We’re not really sure exactly how the drug works in sarcoma but that’s the putative target for the drug. They compared it to a very old drug called dacarbazine, or DTIC, which has been around for about 20-25 years. That drug does have some activity in one of those two sarcoma subtypes, the leiomyosarcoma; in fact dacarbazine works, I would say, in about 10% of those patients but has never really been tested in the liposarcoma setting but it was used as the control arm of this randomised clinical trial.

What’s your thoughts on the findings?

We give a lot of chemotherapy for sarcoma. The standard drug chemotherapy involves usually two drugs, one’s called doxorubicin or called adriamycin and another drug called ifosfamide or Ifex. We give that with a drug called mesna which protects the bladder from the side effects of the chemotherapy. The regimen is called the AIM regimen, A-I-M, we like mnemonics in oncology so AIM is a drug therapy. If you give that drug there have been a number of major randomised clinical trials comparing A-I-M, AIM, to just A by itself, adriamycin. In fact, a European trial just published in the last year and a half in Lancet Oncology, a huge study, large numbers of patients and, guess what, despite the toxicity of AIM no survival benefit over adriamycin by itself. So the question is do we have drugs that actually make people live longer in sarcoma and up to now, in fact, there has never been a major randomised clinical trial like the one we had with eribulin verses dacarbazine that’s ever shown that patients live longer with the chemotherapy drug in sarcoma and that’s what makes this study so special. A drug that makes people live longer. Two months, that’s not a lot of time but in the field of sarcoma that actually is considered a major advance because never in the history of oncology have we had a drug that shows the patient lives longer with chemotherapy. The chemotherapy can palliate, it can make people feel better but, then again a very toxic drug, how to balance palliation versus toxicity of chemotherapy. But here we have a drug that really shows a survival benefit for the first time in a rare cancer sarcoma.

How do you think this could affect cancer doctors and their practice?

It will change practice. Clearly for patients who fail the standard chemotherapy the standard chemotherapy is still the adriamycin ifosfamide drug therapy. In fact, the drug was only tested in patients who failed the standard, even though the standard has never prolonged survival, that’s still the standard chemotherapy for first and second line treatment for patients with metastatic soft tissue tumours or connective tissue cancers. So for patients who fail the standard chemotherapies, these more toxic drugs, there now is eribulin for patients who failed that. We do not know whether it should be used earlier in the treatment of the disease, should it be used instead of those drugs? That data we don’t know. Those will be future clinical trials. But clearly for people looking for a second line therapy, those who fail a first line treatment, eribulin is now a major indication for at least two sarcomas. We have to be very specific about that. This study was only for leiomyo and adipocyte or liposarcomas. There are 48 other sarcoma subtypes not included in this trial, we don’t know if the drug works effectively in those. But for those two subtypes which are probably the two most common sarcomas, liposarcoma and leiomyosarcoma, this drug clearly shows an indication for people who fail a first line indication, first line therapy.

What is the take home message?

Neil Armstrong said a famous statement when he landed on the moon and I’ll modify it first for patients we treat with sarcoma: a small step for cancer but a giant step for sarcoma.

Do you see light at the end of the tunnel for other sarcomas?

There’s no reason to think this shouldn’t work in all the other sarcomas as well but we still need that data in clinical trials to prove that point. At least we have a small step in the right direction. I do see light, I have had no light up to now so to have something that actually makes people live longer, of course that’s light, that’s a step in the right direction. Now we know to move at least in the direction of the light.