Original Research| Volume 101, P123-133, September 2018

Palbociclib plus endocrine therapy in older women with HR+/HER2– advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies


      • We studied palbociclib plus endocrine therapy (ET) for older HR+/HER2– advanced breast cancer (ABC) patients.
      • Palbociclib improved progression-free survival in older patients irrespective of prior treatment status.
      • Patient-reported quality of life was maintained.
      • Palbociclib plus ET has a favourable safety profile in older patients.
      • Palbociclib plus ET is an effective treatment option for older ABC patients.



      Because incidence of breast cancer and comorbidities increase with age, it is important to determine treatment benefit in elderly patients. We evaluated outcomes with palbociclib plus endocrine therapy in patients aged ≥65 years.


      Data were pooled from three randomised studies (NCT00721409, NCT01740427 and NCT01942135) of women with HR+/HER2− advanced breast cancer (ABC). In PALOMA-1 (open-label) and PALOMA-2 (double-blind, placebo-controlled), treatment-naïve patients received palbociclib plus letrozole or letrozole alone. In PALOMA-3 (double-blind, placebo-controlled), patients with endocrine-resistant disease received palbociclib plus fulvestrant or fulvestrant alone.


      Among 528 patients treated with palbociclib plus letrozole and 347 treated with palbociclib plus fulvestrant, 218 (41.3%) and 86 (24.8%), respectively, were aged ≥65 years. Versus endocrine therapy alone, median progression-free survival was significantly improved in patients aged 65–74 years (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.45–0.97; P = 0.016) and ≥75 years (HR, 0.31; 95% CI, 0.16–0.61; P<0.001) receiving palbociclib plus letrozole and in patients aged 65–74 years (HR, 0.27; 95% CI, 0.16–0.48; P<0.001) receiving palbociclib plus fulvestrant; few patients aged ≥75 years received palbociclib plus fulvestrant (HR, 0.59; 95% CI, 0.19–1.8; P = 0.18). Patient-reported functioning and quality of life was maintained. No clinically relevant differences in palbociclib exposure were observed between age groups. Although myelosuppression was more common among patients aged ≥75 years, incidence of grade ≥III myelosuppression was similar across age groups, and febrile neutropenia was uncommon (≤2.4%); no new safety concerns were identified in older patients.


      Palbociclib plus endocrine therapy is an effective, well-tolerated treatment for older patients with ABC.


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        • Bergen E.S.
        • Tichy C.
        • Berghoff A.S.
        • et al.
        Prognostic impact of breast cancer subtypes in elderly patients.
        Breast Cancer Res Treat. 2016; 157: 91-99
        • Kartal M.
        • Tezcan S.
        • Canda T.
        Diagnosis, treatment characteristics, and survival of women with breast cancer aged 65 and above: a hospital-based retrospective study.
        BMC Womens Health. 2013; 13 (Epub): 34
        • Biganzoli L.
        • Wildiers H.
        • Oakman C.
        • et al.
        Management of elderly patients with breast cancer: updated recommendations of the International Society of Geriatric Oncology (SIOG) and European Society of Breast Cancer Specialists (EUSOMA).
        Lancet Oncol. 2012; 13: e148-e160
        • Muss H.B.
        Coming of age: breast cancer in seniors.
        Oncologist. 2010; 15: 57-65
        • NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines)
        Breast cancer. V2.0.
        2013 (Available at:)
        • Fry D.W.
        • Harvey P.J.
        • Keller P.R.
        • et al.
        Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts.
        Mol Cancer Ther. 2004; 3: 1427-1438
        • Toogood P.L.
        • Harvey P.J.
        • Repine J.T.
        • et al.
        Discovery of a potent and selective inhibitor of cyclin-dependent kinase 4/6.
        J Med Chem. 2005; 48: 2388-2406
        • Finn R.S.
        • Dering J.
        • Conklin D.
        • et al.
        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. 2009; 11: R77
        • Finn R.S.
        • Crown J.P.
        • Lang I.
        • 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. 2015; 16: 25-35
        • Cristofanilli M.
        • Turner N.C.
        • Bondarenko I.
        • 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. 2016; 17: 425-439
        • Turner N.C.
        • Ro J.
        • Andre F.
        • et al.
        Palbociclib in hormone-receptor-positive advanced breast cancer.
        N Engl J Med. 2015; 373: 209-219
        • Finn R.S.
        • Martin M.
        • Rugo H.S.
        • et al.
        Palbociclib and letrozole in advanced breast cancer.
        N Engl J Med. 2016; 375: 1925-1936
        • IBRANCE (palbociclib)
        Summary of product characteristics.
        Pfizer Limited; Sandwich, Kent, UK2017
        • IBRANCE® (palbociclib)
        Full prescribing information.
        Pfizer Inc, New York, NY, USA2017
        • Wildiers H.
        • Kunkler I.
        • Biganzoli L.
        • et al.
        Management of breast cancer in elderly individuals: recommendations of the International Society of Geriatric Oncology.
        Lancet Oncol. 2007; 8: 1101-1115
        • Yancik R.
        • Ries L.A.
        Cancer in older persons: an international issue in an aging world.
        Semin Oncol. 2004; 31: 128-136
        • Lewis J.H.
        • Kilgore M.L.
        • Goldman D.P.
        • et al.
        Participation of patients 65 years of age or older in cancer clinical trials.
        J Clin Oncol. 2003; 21: 1383-1389
        • Bernardi D.
        • Errante D.
        • Gallligioni E.
        • et al.
        Treatment of breast cancer in older women.
        Acta Oncol. 2008; 47: 187-198
      1. Turner NC, André F, Cristofanilli M, et al. Treatment postprogression in women with endocrine-resistant HR+ HER2– advanced breast cancer who received palbociclib plus fulvestrant in PALOMA-3. In: 39th Annual San Antonio breast cancer symposium (SABCS) December 6–10, 2016; San Antonio, TX, USA.

        • Balducci L.
        Myelosuppression and its consequences in elderly patients with cancer.
        Oncology (Williston Park). 2003; 17: 27-32
        • Harbeck N.
        • Iyer S.
        • Turner N.
        • et al.
        Quality of life with palbociclib plus fulvestrant in previously treated hormone receptor-positive, HER2-negative metastatic breast cancer: patient-reported outcomes from the PALOMA-3 trial.
        Ann Oncol. 2016; 27: 1047-1054
        • Van Leeuwen B.L.
        • Rosenkranz K.M.
        • Feng L.L.
        • et al.
        The effect of under-treatment of breast cancer in women 80 years of age and older.
        Crit Rev Oncol Hematol. 2011; 79: 315-320
        • Malik M.K.
        • Tartter P.I.
        • Belfer R.
        Undertreated breast cancer in the elderly.
        J Cancer Epidemiol. 2013; 2013: 893104
        • Yancik R.
        • Wesley M.N.
        • Ries L.A.
        • Havlik R.J.
        • Edwards B.K.
        • Yates J.W.
        Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older.
        JAMA. 2001; 285: 885-892
        • Durairaj C.
        • Ruiz-Garcia A.
        • Gauthier E.R.
        • et al.
        Palbociclib has no clinically relevant effect on the QTc interval in patients with advanced breast cancer.
        Anticancer Drugs. 2018; 29: 271-280
        • Yu Y.
        • Loi C.M.
        • Hoffman J.
        • Wang D.
        Physiologically based pharmacokinetic modeling of palbociclib.
        J Clin Pharmacol. 2017; 57: 173-184