Clinical effects of prior trastuzumab on combination eribulin mesylate plus trastuzumab as first-line treatment for human epidermal growth factor receptor 2 positive locally recurrent or metastatic breast cancer: results from a Phase II, single-arm, multicenter study

Abstract

Eribulin mesylate, a novel nontaxane microtubule dynamics inhibitor in the halichondrin class of antineoplastic drugs, is indicated for the treatment of patients with metastatic breast cancer who previously received ≥2 chemotherapy regimens in the metastatic setting. Primary data from a Phase II trial for the first-line combination of eribulin plus trastuzumab in human epidermal growth factor receptor 2 positive patients showed a 71% objective response rate and tolerability consistent with the known profile of these agents. Here, we present prespecified analyses of efficacy of this combination based on prior trastuzumab use. Patients received eribulin mesylate 1.4 mg/m2 (equivalent to 1.23 mg/m2 eribulin [expressed as free base]) intravenously on days 1 and 8 plus trastuzumab (8 mg/kg intravenously/cycle 1, then 6 mg/kg) on day 1 of each 21-day cycle. Objective response rates, progression-free survival, and tolerability were assessed in patients who had and had not received prior adjuvant or neoadjuvant (neo/adjuvant) trastuzumab treatment. Fifty-two patients (median age: 59.5 years) received eribulin/trastuzumab for a median treatment duration of ~31 weeks; 40.4% (n=21) had been previously treated with neo/adjuvant trastuzumab prior to treatment with eribulin plus trastuzumab for metastatic disease (median time between neo/adjuvant and study treatment: 23 months). In trastuzumab-naïve patients (n=31) compared with those who had received prior trastuzumab, objective response rate was 77.4% versus 61.9%, respectively; duration of response was 11.8 versus 9.5 months, respectively; clinical benefit rate was 87.1% versus 81.0%, respectively; and median progression-free survival was 12.2 versus 11.5 months, respectively. The most common grade 3/4 treatment-emergent adverse events (occuring in ≥5% of patients) in patients who received prior trastuzumab versus trastuzumab naïve patients, respectively, were neutropenia (47.6% vs 32.3%), peripheral neuropathy (14.3% vs 25.8%), febrile neutropenia (14.3% vs 3.2%), fatigue (9.5% vs 6.5%), nausea (9.5% vs 0%), vomiting (9.5% vs 3.2%), and leukopenia (9.5% vs 3.2%). In patients with human epidermal growth factor receptor 2 positive metastatic breast cancer, first-line eribulin/trastuzumab treatment demonstrated substantial antitumor activity and was well tolerated, regardless of prior neo/adjuvant trastuzumab treatment.

The safety of eribulin for the treatment of metastatic breast cancer

“…Eribulin has been shown to be more effective in the earlier-line setting after anthracycline and taxane treatment [65], a result that is expected given the decline in treatment efficacy seen in MBC as patients undertake more lines of therapy [66]. As a result, we are likely to see eribulin used in earlier lines of treatment, which is supported by data from clinical trials investigating its use in first-line regimens [34,[67][68][69].…”

“…The safety profile of eribulin means that it is the ideal partner for combination therapies. The results of a few of these combination studies have been reported, and show manageable toxicity profiles, but the majority of these are in small populations (<60 patients) [34,67,[72][73][74][75][76][77][78]. Larger studies of combination therapy are required.…”

Real‐life activity of eribulin mesylate among metastatic breast cancer patients in the multicenter national observational ESME program

“…It is possible that suboptimal treatment of HER2-positive tumors could have induced negative results reported in the pivotal studies of EM in MBC. At the same time, phase II trials evaluating the combination of EM with anti-HER2 targeted therapies, such as trastuzumab [23][24][25] or the trastuzumab-pertuzumab doublet 26,27 reported a favorable safety profile, and interesting response rates, warranting additional investigations and a better definition of the place of such combinations in the HER2-positive MBC therapeutic strategy. of randomized trials to the general population.…”

Phase II Clinical Trial of First-line Eribulin Plus Trastuzumab for Advanced or Recurrent HER2-positive Breast Cancer

“…In a Phase II study of a combination regimen of eribulin and trastuzumab in 52 patients with metastatic breast cancer who previously received ≥2 chemotherapy regimens in the metastatic setting (14), Puhalla et al reported a RR of 59.3% and PFS of 9.2 months, as well as no increase in synergistic adverse events due to the combined regimen. Although that study enrolled patients who had previously received trastuzumab, the efficacy and safety results were comparable to those of our study.…”