This article is more than 5 years old. Information may no longer be current.
Eribulin improves survival for patients with advanced liposarcoma, leiomyosarcoma
Click Here to Manage Email Alerts
CHICAGO – The chemotherapy drug eribulin conferred a 2-month median OS improvement in previously treated patients with advanced intermediate or high grade liposarcoma or leiomyosarcoma compared with dacarbazine, according to results of a phase 3 trial presented at the ASCO Annual Meeting.
These data represent the first randomized phase 3 study to demonstrate an improvement in OS in patients with aggressive liposarcoma or leiomyosarcoma, according to study background.
Patrick Schöffski, MD, MPH, head of the department of general medical oncology and the laboratory of experimental oncology at the University Hospitals Leuven, Belgium, and colleagues previously demonstrated in a phase 2 study that 32% of patients with leiomyosarcoma and 47% of patients with adipocytic sarcoma who were treated with eribulin (Halaven, Eisai) — a microtubule dynamics inhibitor that blocks cell division — achieved 12-week PFS.
“Soft-tissue sarcomas are relatively rare and can be very difficult to treat,” Schöffski said in a press release. “The efficacy of available drugs for initial therapy is very unsatisfactory, and patients whose disease progresses despite two or more lines of treatment have a very poor prognosis.
“For a disease where such few treatment options exist, a 2-month improvement in survival is significant. The more treatments our patients have access to, the better their chances of improving life expectancy.”
The analysis included 452 patients (67% female; 79% younger than age 65 years). Researchers randomly assigned 228 patients to 1.4 mg/m² eribulin intravenously on days 1 and 8 every 21 days and 224 patients to 850 mg/m² to 1200 mg/m² dacarbazine intravenously on day 1 every 21 days. Patients received treatment until disease progression.
OS served as the study’s primary endpoint and median PFS, 12- week PFS and safety served as secondary endpoints.
Median OS was 13.5 months in the eribulin group compared with 11.5 months in the dacarbazine group (HR = 0.77; 95% CI, 0.62-0.95).
PFS was 2.6 months in both treatment cohorts (HR = 0.88; 95% CI, 0.71-1.09). Thirty-three percent of patients who received eribulin achieved 12-week PFS and compared with 29% of patients assigned dacarbazine.
More patients in the eribulin arm required dose reductions (26% vs. 14%). Further, 8% of the patients assigned eribulin and 5% of the patients assigned dacarbazine discontinued treatment due to a drug-related adverse event.
The most common adverse events associated with eribulin included neutropenia (44%), pyrexia (28%), peripheral sensory neuropathy (20%) and alopecia (35%). Of these adverse events, 63% were grade 3, 26% were grade 4 and 4% were fatal.
Adverse events occurred less frequently in the dacarbazine arm; however, thrombocytopenia occurred in more patients treated with dacarbazine than eribulin (29% vs. 6%).
“Generally speaking, metastatic soft tissue sarcoma is a relatively chemotherapy-insensitive disease over all histology types with only a few exceptions,” Schöffski said. “This study was conceptually based on a paper we published in 2011 in The Lancet Oncology [Schöffski P, et al. Lancet Oncol. 2011;doi:10.1016/S1470-2045(11)70230-3.]. We looked in the EORTC academic framework into the activity of eribulin in four different subgroups of soft tissue sarcomas, and the leiomyosarcomas and liposarcomas gave the strongest efficacy signal in that phase 2 study. So, it was a strategic decision to focus on these two relatively common subtypes of soft tissue sarcomas in this huge 452-patient global phase 3 trial.” – by Anthony SanFilippo
Reference:
Schöffski P, et al. Abstract LBA10502. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.
Disclosure: This study was funded by Eisai. Schöffski reports speakers bureau and consulting/advisory roles with and honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, GlaxoSmithKline, iTeos Therapeutics, Mundipharma, Novartis, Pique, Plexxikon, Prime Oncology, SERVIER, Swedish Orphan Biovitrum, Threshold Pharmaceuticals and ThromboGenics. Please see the abstract for a complete list of the other researchers’ relevant financial disclosures.
Perspective
Back to Top
Gary K. Schwartz, MD
Oncologists for sarcoma give a lot of chemotherapy for palliation — that is, to improve symptoms controlling the cancer. But we’ve never had a study along these roads that show prolonged survival. We tell patients that we’re going to help make them feel better, but when it gets down to it, many of these drugs won’t make them live longer. A standard drug combination is doxorubicin and ifosfamide and mesna, or AIM, which every sarcoma specialist administers.
There’s a randomized study published in The Lancet Oncology comparing that combination vs. the single agent doxorubicin (Judson I, et al. Lancet Oncol. 2014; doi:10.1016/S1470-2045(14)70063-4.). This study was done twice because the first time they did the study nobody believed the results. The second time — guess what they found? — there also was horrible toxicity and no survival benefit. So, two drugs are better than one drug? It could never be shown.
Now we have for the first time a randomized study showing that patients actually live longer with a drug. Why is this? That’s another question. Liposarcomas are characterized by two critical genes that are overexpressed — CDK4 and another gene called MDM2. We don’t understand the science as to why eribulin works in this disease. I find it frustrating because I thought I understood the science, and now I don’t. Leiomyosarcomas can be chemotherapy sensitive, but, now we have a survival benefit. It’s a small step for cancer, but really is a large step for sarcoma —even 2 months has never been shown in a randomized setting like this.
We have to try to understand how we get a survival benefit from chemotherapy in sarcoma in order to help us to figure out how to develop it and to build on it. It is a building block. What do we add to eribulin for leiomyosarcomas and liposarcomas? Where do we go from here? It’s going to be complicated because eribulin has toxicities, which brings up the question of quality. Do we have to modify the drug because patients get neutropenia? Do we have to add growth factors? That will increase the cost. What is the cost of adding 2 months of life vs. more drug? There has to be an analysis of that data.
We also have to be careful how we develop these combinations. Maybe immunotherapy should be combined with it, which might be a step forward that won’t affect the bone marrow and won’t worsen the neuropathy. We haven’t even begun to understand what the role of immunotherapy is in sarcoma. We have to be creative to build on this study as a backbone for future drug development.
Click Here to Manage Email Alerts