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Trastuzumab/Eribulin Combo Safe and Effective in HER2-Positive Breast Cancer

Silas Inman @silasinman
Published: Monday, Mar 10, 2014

Debu Tripathy, MD

Debu Tripathy, MD

The first-line combination of trastuzumab and eribulin mesylate demonstrated an objective response rate (ORR) of 71.2% with a median progression-free survival (PFS) of 11.6 months in patients with HER2-positive advanced breast cancer, according to final results from a phase II study presented in a poster session at MBCC.

“Patients that have HER2-positive disease are now being treated with pertuzumab and trastuzumab in the first-line, T-DM1 in the second-line, at some point maybe lapatinib, or maybe capecitabine plus lapatinib,” said Debu Tripathy, MD, a professor of Medicine and co-leader of the Women’s Cancers Program at Norris Comprehensive Cancer Center at the University of Southern California, in an interview with OncLive TV at MBCC. “Many of these patients are candidates for even further therapy. They’re still in good shape and they’ll still potentially be responsive to other treatments. This is where we may need further chemotherapy-partner data.”

The study enrolled 52 patients with locally recurrent or metastatic HER2-positive breast cancer. Approximately half of the patients enrolled had received treatment with chemotherapy and 42.3% of patients had received prior trastuzumab or lapatinib.

On days 1 and 8, patients received eribulin at 1.4 mg/m2 with trastuzumab at a loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses on day 1 of every 21 days for 6 cycles. The primary endpoint was ORR with secondary endpoints examining safety and PFS.

The ORR was 71.2% (95% CI, 56.9-82.9), with three patients experiencing a complete response (5.8%) and 34 patients with a partial response (65.4%) by investigator assessment. The stable disease rate was 25% (13 patients) for a total disease control rate of 96.2% (95% CI, 86.8-99.5).

The median time to a complete or partial response with the combination was 1.3 months (95% CI, 1.2-1.4) with a median duration of response of 11.1 months (95% CI, 6.7- 17.8). The 12-month PFS rate was 49%.

A total of 45 patients completed the full six cycles of treatment. Nine patients discontinued or stopped treatment, including one treatment-related death due to chronic heart failure. Overall, the toxicity was consistent with established safety profiles for eribulin and trastuzumab.

“One of the challenges is to make sure we’re not creating a new problem for our patients when they’re on long-term therapy,” said Tripathy. “We have very little data regarding the comparative neuropathy induced by taxanes and eribulin. There is some data as to how quickly it comes on, how quickly it resolves, and those characteristics seem to be favorable with eribulin.”

In the study, the most commonly occurring all-grade side effects were alopecia (88.5%), fatigue (69.2%), peripheral neuropathy (69.2%), and neutropenia (59.6%). The most common grade 3/4 adverse events were neutropenia (38.5%) and peripheral neuropathy (26.9%).

Peripheral neuropathy led to treatment discontinuations in 13.5% of patients and dose reductions in 19.2% of patients. Neutropenia led to dose reductions in 11.5% of patients and dose interruptions in 21.2% of patients.

“I think the bottom line is that you need to monitor and certainly inform patients of these side effects,” said Tripathy. “Generally speaking, the worse the toxicity gets the more long-standing it may be, and so monitoring and stopping it when it gets to be grade 2, or holding it, or attenuating dosing is critical.”

Eribulin was initially approved based on the open-label, randomized, phase III EMBRACE trial that compared eribulin to physician’s choice in heavily pretreated patients with metastatic breast cancer. In this setting, physician’s choice included several treatments, such as hormonal therapy, palliative care, and chemotherapy. The trial found that overall survival (OS) was significantly prolonged by single-agent eribulin.

More recently, eribulin was compared to capecitabine as a second-line treatment for patients with HER2-negative metastatic breast cancer. This trial did not find a significant advantage for eribulin over capecitabine, in terms of PFS or OS. However, a subset analysis indicated a trend toward benefit with eribulin in patients with triple-negative breast cancer, which is currently an area of unmet need.

“In later lines of therapy, we do know that eribulin is a drug that has been shown to confer a survival advantage, and it was approved on that basis,” Tripathy said. “What we need is to identify markers that tell us which drug works for which patient.”

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