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Eribulin in combination with bevacizumab as second-line treatment for HER2-negative metastatic breast cancer progressing after first-line therapy with paclitaxel and bevacizumab: a multicenter, phase II, single arm trial (GIM11-BERGI).

ABSTRACT:

Background

We evaluated the efficacy and safety of the nontaxane microtubule dynamics inhibitor eribulin plus the humanized anti-VEGF monoclonal antibody bevacizumab in a novel second-line chemotherapy scheme in HER2-negative metastatic breast cancer (MBC) patients progressing after first-line paclitaxel and bevacizumab.

Patients and methods

This is a multicenter, single-arm, Simon's two-stage, phase II study. The primary endpoint was the overall response rate, considered as the sum of partial and complete response based on the best overall response rate (BORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and clinical benefit rate.

Results

A total of 58 of the 61 patients enrolled in the study were evaluable for efficacy. The BORR was 24.6% (95% CI 14.5-37.3). The clinical benefit rate was 32.8% (95% CI 21.3-46.0). The median PFS was 6.2 months (95% CI 4.0-7.8), and median OS was 14.8 months (95% CI 12.6-22.8). Overall, adverse events (AEs) were clinically manageable and the most common AEs were fatigue, paresthesia, and neutropenia. Quality of life was well preserved in most patients.

Conclusions

The results of this study suggest that second-line therapy with bevacizumab in combination with eribulin has a meaningful clinical activity and may represent a potential therapeutic option for patients with HER2-negative MBC.

SUBMITTER: De Angelis C

PROVIDER: S-EPMC7900694 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Previous prospective studies have shown that eribulin improves the survival in patients with metastatic breast cancer (MBC). However, the optimal timing of its administration to achieve the longest extended survival and the efficacy of using eribulin monotherapy as earlier-line chemotherapy are yet unclear. Methods: We identified all consecutive female patients with MBC who received any chemotherapeutic intervention for metastatic disease at our institution between July 2012 and December 2017, excluding patients with HER2-positive disease. Those who received eribulin monotherapy for MBC were classified under the eribulin cohort, whereas those who never received eribulin were included in the non-eribulin (Non-E) cohort. Among the patients in the eribulin cohort, those who received eribulin as the first- or second-line chemotherapy for MBC were further classified under the earlier-line eribulin (EE), and otherwise classified under the later-line eribulin (LE) cohorts. The survival of patients was assessed using the log-rank test. A multivariable Cox proportional hazards model was used to assess the independent efficacy and timing of eribulin monotherapy. The inverse probability of treatment weighting (IPTW) estimate was utilized to compare the EE and LE cohorts. Results: Of the 507 patients who were initially screened, 226 were included after an intensive chart review: 93, 49, and 84 patients were included in the Non-E, EE, and LE cohorts, respectively. The eribulin cohort showed significantly longer overall survival than the Non-E cohort (30.3 vs. 22.2 months, p = 0.0217). No significant difference was observed in the progression-free survival of the EE and LE cohorts (3.4 vs. 4.4 months, p = 0.1337) after adjusting for clinically relevant factors using IPTW estimates. LE cohort showed good overall survival (OS) compared with patient group of Non-E and EE by log-rank testing (p = 0.0398), although multivariate analysis did not demonstrate eribulin administration timing as an independent prognostic factor of OS. OS was defined from the initiation of first-line chemotherapy date. Conclusions: Our data provided additional insights regarding the use of eribulin monotherapy as earlier-line chemotherapy. However, the optimal timing of eribulin monotherapy for MBC was not determined in the current study.

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