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Eribulin Mesylate Plus Trastuzumab Yields High Response Rates as First-Line Metastatic Breast Cancer Treatment

TOP - February 2014, Vol 7, No 1

For the first-line treatment of HER2-positive metastatic breast cancer, the combination of eribulin mesylate and trastuzumab yields higher response rates, with manageable toxicity.

In the phase 3 EMBRACE trial, eribulin mesylate demonstrated a survival benefit relative to commonly used agents in women with metastatic breast cancer who had received at least 2 prior regimens, which led to the drug’s approval in 2010 for later lines of treatment.

At the 2013 San Antonio Breast Cancer Symposium, Sharon Wilks, MD, of US Oncology–Cancer Care Centers of South Texas, presented the final results for the primary and secondary end points of a multicenter phase 2 trial that explored the efficacy and safety of eribulin mesylate plus trastuzumab as first-line treatment for patients with locally recurrent or metastatic HER2-positive breast cancer.

“This is the first study to look at this combination,” Wilks said in an interview. She noted that numerous studies have shown that trastuzumab is “still active” in combination with later lines of chemotherapy. “This is another piece of evidence that supports that,” she said.

Study Details

Among the 52 patients in the study (mean age 59), 45 completed treatment; 8 patients remained in the extension phase of the treatment at the time of data cut-off.

Patients received 6 cycles of eribulin mesylate 1.4 mg/m2 on days 1 and 8 of each 21-day cycle and standard-dose trastuzumab on day 1 of each cycle. Dose reductions for eribulin, but not for trastuzumab, were permitted, and eribulin could be considered as monotherapy if trastuzumab was discontinued. The primary end point was antitumor activity (objective response rate) of eribulin plus trastuzumab.

High Response Rates Observed

Investigators determined the objective response rate to be 71.2%, the disease-control rate to be 96.2% (complete and partial responses plus stable disease), and the clinical benefit rate (complete and partial responses plus stable disease >6 months) to be 84.6%.

By investigator assessment, complete responses were observed in 5.8% of patients and partial responses in 65.4%.

The waterfall plot, showing the change in the total sum of target lesion diameters from baseline to postbaseline nadir, revealed that all but 2 patients had some degree of tumor shrinkage. The median percent change from baseline was –62.4%, Wilks reported.

Encouraging Progression-Free Survival, Manageable Toxicity

Median progression-free survival (PFS) was 11.6 months, and the estimated PFS rates were 96% at 3 months, 82% at 6 months, 67% at 9 months, and 49% at 12 months. For all patients, median time to response was 1.3 months and median duration of response was 11.1 months.

“This is a great PFS,” Wilks said, “and it’s an easy regimen to give and well tolerated.”

Patients received a median of 10 cycles of eribulin and 11 of trastuzumab, indicating that most patients given this regimen are able to complete treatment. Treatment-emergent adverse events were reported by all patients, but they were manageable, according to Wilks.

“Most patients don’t have much nausea and vomiting, and their overall condition remains good, but they do lose their hair,” she acknowledged.

Alopecia was observed in 88.5% of patients, fatigue in 69.2% (7.7% grade 3-4), peripheral neuropathy in 69.2% (26.9% grade 3-4), and neutropenia in 59.6% (38.5% grade 3-4).

“What is novel about this drug, however, is that even when patients continue therapy their hair grows back after 3 to 4 cycles, and you don’t usually see that with other drugs that cause alopecia,” she added.

She acknowledged that neuropathy can be difficult for patients, “but keep in mind that these patients have had other drugs that affect the nerve beds, and that may be a reason why we see neuropathy,” she said. “When we adjust the dosing or hold the drug for neuropathy, patients usually return to baseline.”

In the study, 40% needed dose reductions, 42.3% had dose interruptions or delays, and 21.2% discontinued the study medication(s).

“The take-away message from this study is this: when you are looking for later-line options, after you have used the [FDA-approved] up-front treatments—pertuzumab (Perjeta) and ado-trastuzumab emtansine (Kadcyla)—this is an active and tolerable third- or fourth-line regimen,” Wilks suggested.


Wilks S, Puhalla S, O’Shaughnessy J, et al. Phase 2, multicenter, single-arm study of eribulin mesylate + trastuzumab as first-line therapy for locally recurrent or metastatic HER2-positive breast cancer. Presented at: San Antonio Breast Cancer Symposium; December 13, 2013; San Antonio, TX. Poster P4-12-12.

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