Palbociclib, a CDK4-6 inhibitor, combined with endocrine therapy (ET) is a new standard of treatment for Hormone Receptor-positive Metastatic Breast Cancer. We present the first real-life efficacy and tolerance data of palbociclib plus fulvestrant in this population.
From November 2015 to November 2016, patients receiving in our institution palbociclib + fulvestrant according to the Temporary Authorization for Use were prospectively analyzed.
60 patients were treated accordingly; median age was 61 years; 50 patients (83.3%) had visceral metastasis, and 10 (16.7%) had bone-only disease. Patients had previously received a median of 5 (1–14) lines of treatment, including ET (median 3) and chemotherapy (median 2); 28 (46.7%) received previously fulvestrant and all everolimus. With a median follow-up of 10.3 months, median progression-free survival (mPFS) was 5.8 months (95% CI 3.9–7.3). Patients pretreated with fulvestrant had a similar PFS of 6.4 months (HR 1.00; 95% CI 0.55–1.83; P = 1.00). The most common AEs (adverse events) were neutropenia (93%), anemia (65%), and thrombocytopenia (55%).
In this heavily pretreated population including everolimus, fulvestrant plus palbociclib provides an mPFS of 5.8 months with the same magnitude of benefit for fulvestrant-pretreated patients.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Augereau P, Patsouris A, Bourbouloux E, Gourmelon C, Abadie-Lacourtoisie S, Berton Rigaud D et al (2017) Hormonoresistance in advanced breast cancer: a new revolution in endocrine therapy. Ther Adv Med Oncol 9:335–346. https://doi.org/10.1177/1758834017693195
Hortobagyi GN, Stemmer SM, Burris HA, Yap Y-S, Sonke GS, Paluch-Shimon S et al (2016) Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med 375:1738–1748. https://doi.org/10.1056/NEJMoa1609709
Finn RS, Martin M, Rugo HS, Jones S, Im S-A, Gelmon K et al (2016) Palbociclib and letrozole in advanced breast cancer. N Engl J Med 375:1925–1936. https://doi.org/10.1056/NEJMoa1607303
Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J et al (2017) MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. https://doi.org/10.1200/JCO.2017.75.6155
Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im S-A, Masuda N et al (2016) 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 17:425–439. https://doi.org/10.1016/S1470-2045(15)00613-0
Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X et al (2017) 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. https://doi.org/10.1200/JCO.2017.73.7585
Dickler MN, Tolaney SM, Rugo HS, Cortés J, Diéras V, Patt D et al (2017) MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR+/HER2 − metastatic breast cancer. Clin Cancer Res. https://doi.org/10.1158/1078-0432.CCR-17-0754
Turner NC, Ro J, André F, Loi S, Verma S, Iwata H et al (2015) Palbociclib in hormone-receptor–positive advanced breast cancer. N Engl J Med 373:209–219. https://doi.org/10.1056/NEJMoa1505270
Beaver JA, Amiri-Kordestani L, Charlab R, Chen W, Palmby T, Tilley A et al (2015) FDA approval: palbociclib for the treatment of postmenopausal patients with estrogen receptor-positive, HER2-negative metastatic breast cancer. Clin Cancer Res 21:4760–4766. https://doi.org/10.1158/1078-0432.CCR-15-1185
Dhakal A, Matthews C, Zhang F, Levine EG, Edge SB, Salerno KE et al (2017) Outcome of palbociclib based therapy in hormone receptor positive metastatic breast cancer patients after treatment with everolimus. J Clin Oncol 35:1054. https://doi.org/10.1200/JCO.2017.35.15_suppl.1054
Di Leo A, Ciruelos E, Janni W, Lonning PE, O’Regan R, Hubalek M et al (2015) BELLE-3: A phase III study of the pan-phosphatidylinositol 3-kinase (PI3 K) inhibitor buparlisib (BKM120) with fulvestrant in postmenopausal women with HR+/HER2– locally advanced/metastatic breast cancer (BC) pretreated with aromatase inhibitors (AIs) and refractory to mTOR inhibitor (mTORi)-based treatment. J Clin Oncol 33:TPS626. https://doi.org/10.1200/jco.2015.33.15_suppl.tps626
DeMichele A, Clark AS, Tan KS, Heitjan DF, Gramlich K, Gallagher M et al (2015) CDK 4/6 inhibitor palbociclib (PD0332991) in Rb + advanced breast cancer: phase II activity, safety, and predictive biomarker assessment. Clin Cancer Res 21:995–1001. https://doi.org/10.1158/1078-0432.CCR-14-2258
Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ et al (2009) PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res 11:1
Malorni L, Curigliano G, Minisini AM, Cinieri S, Tondini C, Arpino G et al (2017) A phase II trial of the CDK4/6 inhibitor palbociclib (P) as single agent or in combination with the same endocrine therapy (ET) received prior to disease progression, in patients (pts) with hormone receptor positive (HR+) HER2 negative (HER2 −) metastatic breast cancer (mBC) (TREnd trial). J Clin Oncol 35:1002. https://doi.org/10.1200/JCO.2017.35.15_suppl.1002
Turner N, Andre F, Cristofanilli M, Verma S, Iwata H, Loi S et al (2016) Abstract P4-22-06: treatment postprogression in women with endocrine-resistant HR+/HER2- advanced breast cancer who received palbociclib plus fulvestrant in PALOMA-3. Cancer Res 77:P4–P22
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Conflict of interest
JSF and MC report receiving consulting fees from Pfizer; PA received fees for serving on advisory boards from Pfizer; PDR, JSF, AP, and MC received travel support from Pfizer.
Rights and permissions
About this article
Cite this article
du Rusquec, P., Palpacuer, C., Campion, L. et al. Efficacy of palbociclib plus fulvestrant after everolimus in hormone receptor-positive metastatic breast cancer. Breast Cancer Res Treat 168, 559–566 (2018). https://doi.org/10.1007/s10549-017-4623-8
- Metastatic breast cancer
- HR positive