Efficacy of Palbociclib and Endocrine Treatment in Heavily Pretreated Hormone Receptor-positive/HER2-negative Advanced Breast Cancer: Retrospective Multicenter Trial

Background: The synthesis of CDK4/6 inhibitors with endocrine treatment in two series of treatment has been widely accepted as the standard for patients with estrogen receptor-positive metastatic breast cancer. In spite of this, the activity of CDK4/6 inhibitors in patients with metastatic breast cancer who have progressed despite receiving multiple lines of treatment is not well understood.Aims: To report the activity and safety of a CDK4/6 inhibitor (palbociclib) in patients in whom at least three lines of treatment for ER+ metastatic breast cancer had failed.Study Design: Multicenter retrospective observational cohort study.Methods:Inthisretrospectiveobservationalcohortstudy,weincluded 43 patients who received palbociclib after at least three lines of systemic treatment for ER+/HER2− metastatic breast cancer.Results: The median progression-free survival in our population was 7 months (25th-75th percentile, 4-10), and the median overall survival was 11 months (25th-75th percentile, 6-19). Although there were some adverse events, palbociclib was generally well tolerated, so dose reduction was needed for only six patients (14%).Conclusion: The efficacy of palbociclib among heavily treated hormonereceptor-positive/HER2−patientswithadvancedbreastcancer was acceptable in terms of clinical benefit, and it was generally well tolerated among this population.

PDF

___

1. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 2013;49:1374-403.
2. Boér K. Impact of palbociclib combinations on treatment of advanced estrogen receptor-positive/human epidermal growth factor 2-negative breast cancer. Onco Targets Ther 2016;9:6119-25.
3. Cardoso F, Senkus E, Costa A, Papadopoulos E, Aapro M, André F, et al. 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4). Ann Oncol 2018;29:1634-57.
4. Gradishar WJ, Anderson BO, Balassanian R, Blair SL, Burstein HJ, Cyr A, et al. Breast Cancer, Version 4.2017, NCCN Clinical Practice guidelines in Oncology. J Natl Compr Canc Netw 2018;16:310-20.
5. Osborne CK, Schiff R. Mechanisms of endocrine resistance in breast cancer. Annu Rev Med 2011;62:233-47.
6. Maurer C, Martel S, Zardavas D, Ignatiadis M. New agents for endocrine resistance in breast cancer. Breast 2017;34:1-11.
7. Augereau P, Patsouris A, Bourbouloux E, Gourmelon C, Abadie Lacourtoisie S, Berton Rigaud D, et al. Hormonoresistance in advanced breast cancer: a new revolution in endocrine therapy. Ther Adv Med Oncol 2017;9:335-46.
8. Vidula N, Rugo HS. Cyclin-dependent kinase 4/6 inhibitors for the treatment of breast cancer: a review of preclinical and clinical data. Clin Breast Cancer 2016;16:8-17.
9. Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, et al. Palbociclib in hormone- receptor-positive advanced breast cancer. N Engl J Med 2015;373:209-19.
10. Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol 2019;17:425-39.
11. Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2-advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol 2017;35:2875-84.
12. Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med 2016;375:1738-48.
13. Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised Phase 2 study. Lancet Oncol 2014;16:25-35.
14. Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med 2016;375:1925-36.
15. Ban M, Miše BP, Majić A, Dražić I, Vrdoljak E. Efficacy and safety of palbociclib in heavily pretreated patients with HR+/HER2- metastatic breast cancer. Future Oncol 2018;14:537-44.
16. Battisti NML, Kingston B, King J, Denton A, Waters S, Sita-Lumsden A, et al. Palbociclib and endocrine therapy in heavily pretreated hormone receptor-positive HER2-negative advanced breast cancer: the UK Compassionate Access Programme experience. Breast Cancer Res Treat 2019;174:731-40.