The effectiveness and safety of eribulin therapy in HR-positive HER2-negative metastatic breast cancer post-CDK4/6 inhibitor therapy in Russian clinical practice.

Abstract

e13035 Background: EMPOWER trial demonstrated the benefit of eribulin administrated post CD4/6i in patients (pts) with HR+ HER2-negative (HR+HER2-) metastatic breast cancer (MBC). There are several important limitations to this trial: > 60% of pts were stage IV at the time of treatment initiation, eribulin used in late lines (2L only in 30% pts) and follow-up data were immature. Current study aimed to provide additional data on the real-world effectiveness and safety of eribulin monotherapy in this setting. Methods: Observation study of eribulin monotherapy in standard regimen enrolled 54 pts (median age 56; range 29-79 years) with HR+ HER2- MBC received at least one dose of eribulin post CDK 4/6i in metastatic settings; 24% pts had de novo metastatic BC, 76% - recurrent BC; 77% received palbociclib, 21% ribociclib, 2% both drugs; 49% pts received CDK4/6i with fulvestrant and 51% with AI. CDK4/6i was used: 49% pts in 1L, 36% in 2L, 16% in 3L. Median DOR of CDK4/6i treatment was 9.07 months (range 2-38). 94% pts received anthracyclines and taxanes, eribulin was used in 2L in 60%, 30% in 3L, 8% in 4L, 2% in 5L. The most common sites of metastases (Mts) were bones (78%), liver (73%), lung (56%) and brain (8%); visceral Mts were seen in 90% pts. Median follow-up – 11,5 months (range 3-36). Results: Median cycles of eribulin therapy was 10,5 (range 1-44); objective response rate was seen in 24%, stabilization - 67%, progression - in 9%. Median PFS was 10.0 months, there were no significant differences in the different subgroups (visceral/no visceral; recurrent/de novo BC; age; CDK4/6i as 1L vs 2L, fulvestrant vs AI), p > 0,05. Median PFS was higher in pts with lung Mts vs non-lung (24 vs 9,1 months, p = 0.056). Most common AEs all grades were neutropenia (26%), anemia (9%), asthenia (9%), polyneuropathy (11.1%). AE did not affect the effectiveness of eribulin (p = 0.648). Dose reduction was in 19% pts and did not affect the effectiveness of eribulin (p = 0.612). At median follow-up of 11.5 months, 92.5% of patients still alive. Conclusions: As post-CDK4/6i therapy, eribulin in HR+HER2- MBC pts was effective and well tolerated, regardless of age, line of CDK4/6, CDK 4/6i combination partner. Patients with metastasis to the lung have better mPFS. Results in this real-world population of pts with HR+HER2- MBC were consistent with the EMPOWER study, and support administration of eribulin in 2-3 lines as an effective option for post-CD4/6i pts.

Progression after First-Line Cyclin-Dependent Kinase 4/6 Inhibitor Treatment: Analysis of Molecular Mechanisms and Clinical Data

“…Chemotherapy was chosen for 29.7% of patients, and the use of chemotherapy decreased over time [92]. Eribulin, a tubulin polymerization inhibitor, demonstrated efficacy after CDK4/6is treatment in a Russian study [144], with an mPFS of 10.0 months; the 6-month, 1-year, and 2-year PFSs were 79.5%, 44.8% and 26.5%, respectively.…”

CDK4/6 inhibitor resistance mechanisms and treatment strategies (Review)

“…There are three ongoing clinical trials (NcT04251169, NcT03901339 and NCT04134884) evaluating the efficacy of chemotherapy after cdK4/6 inhibitor resistance in patients with ER + /HER2breast cancer. In addition, eribulin, a tubulin polymerization inhibitor, was reported at the 2021 AScO meeting as a monotherapy for patients with HR + /HER2 -MBc after cdK4/6 inhibitor treatment (100). Therefore, following resistance to endocrine therapy + cdK4/6i for patients with HR + /HER2 -ABc, chemotherapy still remains a usual choice of treatment.…”