Analysis of the efficacy and safety of eribulin therapy in patients with HR+/HER2- metastatic breast cancer pretreated with CDK4/6 inhibitors in real Russian practice
Authors: Kolyadina Irina V. , Abidova Natalia R. , Akopyan Arshak A. , Antonova Galina V. , Arapova Oksana I. , Bobrova Elvira A. , Bolotina Larisa V. , Valiakhmetova Chulpan K. , Vasilevskaya Anna V. , Vladimirova Lyubov Y. , Volkonskiy Mikhail V. , Ganshina Inna P. , Gudkova Irina E. , Dergunov Alexandr S. , Evstigneeva Irina V. , Egurenkova Viktoria S. , Emshanov Aleksei V. , Zhukova Lyudmila G. , Zueva Elena V. , Karabina Elena V. , Kolokolov James J. , Kuzmicheva Svetlana V. , Kuchevskaya Olesya A. , Luev Ivan A. , Maistrenko Ksenia S. , Markizova Elena V. , Marfutov Vasily V. , Medvedev Sergey P. , Merzlikina Yulia I. , Nersesova Tatyana A. , Ovchinnikova Elena G. , Orlova Svetlana A. , Samaneva Natalia Y. , Stativko Olesya A. , Storozhakova Anna E. , Stroyakovskiy Daniil L. , Sultanbaev Alexander V. , Tekeeva Asiat I. , Fadeeva Natalia V. , Fedorova Alina N. , Shalaeva Oksana M. , Shangina Irina A. , Shirokova Oksana N. , Shumskikh Alisa R. , Yakubova Mariam Z. 
Published: May 2021

Relevance. Data on the efficacy of endocrine and chemotherapy regimens in patients with hormone-resistant metastatic breast cancer (mBC) after progression with CDK4/6 inhibitors are limited; the search for an effective therapy regimen in this clinical situation is an urgent task of clinical oncology.
Aim. Evaluate the efficacy and safety of eribulin therapy in patients with HR+/HER2- mBC after progression with CDK4/6 inhibitors; compare the results of the Russian study and the EMPOWER observational study in the USA.
Materials and methods. The Russian observational study included 54 patients (pts) with HR+/HER2- mBC, who were treated with eribulin after CDK4/6 inhibitors in 24 Russian Cancer hospitals. The median age of pts was 56 years; 75.9% of them had recurrent BC, 24.1% de novo BC stage IV; 51.9% of pts had progression with CDK4/6 inhibitors in the first 6 months of therapy (primary endocrine resistance); 48.1% of patients had progression in the period from 6 to 38 months; 89.1% had visceral site of metastases (liver MTS 65.5%, lung MTS 52.8%, brain MTS in 7.5%). Eribulin was used after anthracyclines and taxanes in 94.4% of cases. The efficacy and safety of eribulin therapy in patients with HR+/HER2- mBC after progression with CDK4/6 inhibitors was studied, as well as subgroup analysis according to age, sites of metastasis, and previously treatment options.
Results. Eribulin was prescribed in the standard regimen of 1.4 mg/m2 on days 1 and 8, the interval between cycles was 21 days, the number cyclys of chemotherapy was 144 (median 8, the mean number of cycles 10.5). With a median follow-up of 11.5 months (from 3 to 36 months), 30 patients (55.6%) continue therapy with eribulin at present; therapy was cancelled in 24 patients due to progression in 22 (40.7%) cases, and due to intolerable toxicity in 2 (3.7%) patients. The maximum response to eribulin therapy included partial response (in 11 cases, 24.4%), stable disease (in 30 cases, 66.7%) and progression in 4 (8.9%) patients. Median PFS with eribulin therapy was 10.0 months; the 6-month, 1-year, and 2-year PFS were 79.5%, 44.8% and 26.5%, respectively. Eribulin therapy was equally effective in different subgroups (p0.05) and did not depend on the age of patients, the previously received treatment, the presence of visceral MTS and liver damage. The best response to chemotherapy with eribulin was observed in lung metastases: median PFS 24 months vs 9.1 months, p=0.056. The safety profile was favorable; adverse events were registered in 34.5% of patients, which required dose adjustment in 18.5% of cases. With a median follow-up of 11.5 months, 92.6% of patients remain alive.
Conclusion. Eribulin has demonstrated high efficacy and favorable safety profile in hormone-resistant HER2- mBC in patients with progression when receiving CDK4/6 inhibitor.