Eribulin Shows Efficacy in Leiomyosarcoma, Further Research Needed

Jean-Yves Blay, MD, PhD

A subgroup analysis from a phase III, open-label, randomized study showed that eribulin (Halaven) had comparable activity to dacarbazine (DTIC) in patients with leiomyosarcoma. These results were presented at the recent 2016 ESMO Congress.

In the subgroup of 309 patients with leiomyosarcoma, the median overall survival (OS) was 12.7 months with eribulin versus 13 months with DTIC (HR = 0.93; 95% CI, 0.71-1.20).

Based on previously reported results from the phase III trial, eribulin was approved in January 2016 for unresectable or metastatic liposarcoma in patients who had received a prior anthracycline-containing regimen.

“Even though the drug is not approved for leiomyosarcoma, this proves that we need to work more and further explore the activity of this agent in this very specific patient population,” said lead study author Jean-Yves Blay, MD, PhD.

OncLive: Could you provide an overview of your presentation at ESMO?

In an interview with OncLive, Blay, a professor of Medicine at the Université Claude Bernard, Lyon, France, and the scientific director of the Canceropole Lyon Rhône Alpes, discussed the key points of this subgroup analysis, as well as the current and future state of the treatment landscape for sarcoma and its many subtypes.Blay: I presented a subgroup analysis of a pivotal phase III trial, which tested eribulin versus DTIC in patients with advanced soft tissue sarcoma progressing after a doxorubicin-based regimen. This clinical trial was actually already reported and published some months ago and led to the approval of eribulin for the treatment of liposarcoma in this clinical situation.

Now, what I’m presenting here is a subgroup analysis of the L-sarcoma, which is leiomyosarcoma, which is a complex and difficult-to-treat patient population. Eribulin was found to be equivalent to DTIC in terms of OS and progression-free survival (PFS). This is important because leiomyosarcoma is quite a challenging disease, and DTIC is well known to be an active agent in this setting and is actually incorporated in many first-line chemotherapy regimens, while other regimens are using it more in later stages.

So the observation that eribulin was equivalent in terms of OS, antitumor activity, PFS, and response is very interesting. Even though the drug is not approved for leiomyosarcoma, this proves that we need to work more and further explore the activity of this agent in this very specific patient population.

The activity of the drug was also associated with quite a good tolerance. There were slightly more incidents of neutropenia, less thrombopenia, slightly more alopecia. Overall, it was a very well tolerated treatment, and it was easy to administer.

What makes sarcoma such a difficult disease to treat?

It’s important to remember that there are very few clinical trials in this space. In fact, this is the biggest one demonstrating improvement in OS in patients with advanced sarcoma. So these findings are very important, and this new treatment certainly adds something to treatment of patients with advanced L-sarcoma.Eribulin was tested in L-sarcoma, which represents about 15% of all sarcomas, including advanced sarcoma. There’s a large group of other sarcomas, which probably includes more than 80 different histological subtypes, for probably more than 200 molecular subtypes or something like that, for which we have not yet explored eribulin. And that’s something we should probably do in the future, considering the activity of the agent in L-sarcoma.

What are the next steps following the results of this subgroup analysis?

What would you like to see in the treatment landscape of sarcoma in the next 5 to 10 years?

Indeed, sarcoma remains a difficult-to-treat patient population because it’s not a homogenous group of tumors. It’s quite heterogeneous in terms of clinical presentation, histology, and molecular and clinical behavior. Therefore, it’s extremely difficult to treat, and it’s very rare. Making clinical trials in this patient population has always been quite challenging, so it’s going to be a challenge for future research, as well.The next step regarding eribulin would probably be to explore the agent first earlier in patients with L-sarcoma and also to explore the agent in other sarcoma subtypes, particularly those with limited treatment options. That’s the case for soft tissue sarcoma and probably for bone sarcoma as well, and I’d like to explore that further.I think the treatment landscape for sarcoma has really evolved in recent years. We’ve gone from a situation where we had a one-size-fits-all approach—where patients were all treated with the same chemotherapy regimens—to a situation where we probably have to adapt chemotherapy and targeted treatments for those molecular subtypes. That’s completely changing the landscape.

Are there any other trials in sarcoma that you’re excited about?

It’s also very difficult from a clinical research standpoint. We need to think more about how to adapt this rarity to development of new agents because sarcomas are rare, but there have been very good models to develop new treatments where we have significant activity.There is an important clinical trial that has been done by a corporation of national sarcoma groups together with the support of European Commission, which was called EUROSARC. So this includes Italian, Spanish, French, and British sarcoma groups, and they all did a randomized clinical trial, which is going to be presented soon. It shows that neoadjuvant chemotherapy is associated with improvement in OS in selected sarcoma subtypes with large tumors. That is a very interesting result because that puts chemotherapy as a possible standard for the future treatment of these patients. That’s very exciting.

There are also some papers of interest that show something we already knew, but can now be measured. The treatment of these patients is done better at reference centers and centers with a high volume of treatment—centers with experience, in other words. This may be a major prognostic factor associated with better outcome, and that needs to be integrated into our practice.

Blay J, Schoffski P, Bauer S, et al. Subgroup analysis of leiomyosarcoma (LMS) patients (pts) from a phase 3, open-label, randomized study of eribulin (ERI) versus dacarbazine (DTIC) in pts with advanced liposarcoma (LPS) and LMS. Presented at: 2016 ESMO Congress; October 7-11, 2016; Copenhagen, Denmark. Abstract 1401PD.