Pooled analyses of eribulin in metastatic breast cancer patients with at least one prior chemotherapy

Abstract

Background: Based on data from two multicenter, phase III clinical trials (Studies 301 and 305), eribulin (a microtubule dynamics inhibitor) is indicated in the European Union (EU) for patients with locally advanced or metastatic breast cancer (MBC) after ≥1 prior chemotherapy for advanced disease, including an anthracycline and a taxane in either the adjuvant or metastatic setting. Data from Studies 305 and 301 were pooled to investigate the efficacy of eribulin in various subgroups of patients who matched the EU label, including those with human epidermal growth factor receptor 2 (HER2)-negative and triple-negative disease.

Patients and methods: In Study 305 (NCT00388726), patients were randomized 2:1 to eribulin mesylate 1.4 mg/m(2) (equivalent to eribulin 1.23 mg/m(2) [expressed as free base]) intravenously on days 1 and 8 every 21 days] or treatment of physician's choice after 2-5 prior chemotherapies (≥2 for advanced disease), including an anthracycline and a taxane (in early/advanced setting). In Study 301 (NCT00337103), patients were randomized 1:1 to eribulin (as above) or capecitabine (1.25 g/m(2) orally twice daily on days 1-14 every 21 days) following ≤3 prior chemotherapies (≤2 for advanced disease), including an anthracycline and a taxane. Efficacy end points were investigated in the intent-to-treat population and subgroups, pooled as discussed above.

Results: Overall, 1644 patients were included (eribulin: 946; control: 698); baseline characteristics were well matched. Overall survival was significantly longer with eribulin versus control (P < 0.01), as were progression-free survival and clinical benefit rate (both P < 0.05). Significant survival benefits with eribulin versus control were observed in a wide range of patient subgroups, including HER2-negative or triple-negative disease (all P < 0.05).

Conclusion: Our findings underline the survival benefit achieved by eribulin used according to EU label in the overall MBC population and in various subgroups of interest, including patients with HER2-negative and triple-negative disease.

Keywords: clinical trial; eribulin; metastatic breast cancer; pooled analysis; survival; triple-negative breast cancer.

Figure 1.

OS curves in patients who received eribulin or the comparator drug according to the EU label^a. Hazard ratio is estimated based on the Cox model with stratification factors of region, HER2 status, prior capecitabine use, and study. The median OS is adjusted by study. P value is estimated based on the stratified log-rank test. ^aPatients with locally advanced or MBC who had received one or more prior chemotherapeutic regimens for advanced disease (including an anthracycline and a taxane in either the adjuvant or metastatic setting, unless patients were not suitable for these treatments). CI, confidence interval; EU, European Union; HER2, human epidermal growth factor receptor 2; MBC, metastatic breast cancer; OS, overall survival.

Figure 2.

PFS in patients who received eribulin according to the EU label^a, based on investigator review. HR was estimated based on the Cox model without covariates, with stratification factors: study, region, HER2 status, and prior capecitabine use. For HER2 subgroup analysis, HER2 was not used as a stratification factor. P value is estimated based on the stratified log-rank test. ^aPatients with locally advanced or MBC who had received one or more prior chemotherapeutic regimens for advanced disease (including an anthracycline and a taxane in either the adjuvant or metastatic setting, unless patients were not suitable for these treatments). ^bA significant interaction between study and treatment was observed in this analysis when a treatment*study interaction term was used (P < 0.01; data not shown). CI, confidence interval; ER, estrogen receptor; EU, European Union; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; MBC, metastatic breast cancer; PFS, progression-free survival.

Figure 3.

OS in patients who received eribulin according to the EU label^a. HR was estimated based on the Cox model without covariates, with stratification factors: study, region, HER2 status, and prior capecitabine use. For HER2 subgroup analysis, HER2 was not used as a stratification factor. P value is estimated based on the stratified log-rank test. ^aPatients with locally advanced or MBC who had received one or more prior chemotherapeutic regimens for advanced disease (including an anthracycline and a taxane in either the adjuvant or metastatic setting, unless patients were not suitable for these treatments). ^bA significant interaction between study and treatment was observed in this analysis (P < 0.05; data not shown). Intent-to-treat population. CI, confidence interval; ER, estrogen receptor; EU, European Union; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; MBC, metastatic breast cancer; OS, overall survival.