Eribulin Dose-Modification May Allow for Better Outcomes

February 27, 2015
Leah Lawrence

Women with breast cancer who received first-line eribulin were able to stay on treatment longer and had better outcomes when they received dose modifications.

Women with breast cancer who received first-line treatment with the nontaxane microtubule dynamics inhibitor eribulin mesylate were able to stay on treatment longer and had better clinical outcomes when they received dose modifications during their treatment, according to the results of a poster presented at the 32nd Annual Miami Breast Cancer Conference, held February 26–March 1 in Miami Beach, Florida.

According to the researchers, led by Joyce O’Shaughnessy, MD, of the Texas Oncology–Baylor Charles A. Sammons Cancer Center, and US Oncology, Dallas, Texas, these results suggests that “the use of dose modification to manage adverse events may allow patients to achieve a longer duration of eribulin therapy, which in turn may result in improved outcomes.”

Eribulin mesylate is currently approved for the treatment of metastatic breast cancer in patients who have previously received at least two prior lines of chemotherapy, including a taxane and an anthracycline. Recently though, two phase II studies looked at eribulin as a first-line treatment and showed that the drug had clinical activity with an acceptable toxicity profile.

The first, Study 206, included 56 patients with HER2-negative breast cancer. The second, Study 208, included 52 patients with HER2-positive disease. All patients were assigned to eribulin 1.4 mg/m2 on days 1 and 8 of a 21-day cycle. Patients enrolled in Study 208 also received trastuzumab on day 1 of each cycle.

In this analysis, O’Shaughnessy and colleagues compared outcomes among patients in these two phase II studies who did or did not have eribulin or eribulin/trastuzumab dose modifications during their treatment. Specifically, patients who had grade 3 or 4 toxicities could delay eribulin treatment to allow for recovery, and if toxicities recurred, the dose of the drug could be reduced. Efficacy endpoints of the analysis included overall response rate, stable disease rate, and progression-free survival.

More than half of patients in Study 206 (57%) and Study 208 (71%) had eribulin dose modifications, with a majority due to adverse events. Dose modifications included dose reductions, delays, and interruptions for patients in Study 206 (36%, 38%, and 36%) and Study 208 (40%, 25%, 52%). Patients in both studies had a longer median duration of dosing when dose modification occurred compared with when no modification occurred (Study 206: 29.6 weeks vs 8.9 weeks; Study 208: 37.3 weeks vs 22.1 weeks).  

The researchers noted that dose modification resulted in a lower median relative dose intensity in Study 206 (89.2% vs 99.6%) and Study 208 (87.5% vs 100%). However, patients who had dose modifications had better clinical response rates compared with those patients with no dose modification, including:

• Objective response rate (Study 206: 41% vs 13%; Study 208 76% vs 60%);

• Stable disease (Study 206: 50% vs 42%; Study 208: 22% vs 33%);

• Progression-free survival (Study 206: median 7.6 months vs 2.6 months; Study 208: 13.1 months vs 9.1 months).

The researchers did find higher rates of neutropenia and neuropathy among those patients who had dose modifications made to their regimens; however, they wrote that this was “not unexpected, as neutropenia and neuropathy are among the adverse events for which dose reductions are recommended.”

Reference

O’Shaughnessy JA, Puhalla S, McIntyre K, et al. Outcomes in patients with and without dose reductions during first-line eribulin mesylate therapy for HER2-positive or HER2-negative locally recurrent or MBC. Paper presented at: 32nd Annual Miami Breast Cancer Conference; February 2015; Miami, Florida.

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