Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial
Tóm tắt
Determine the efficacy and safety of first-line ribociclib plus letrozole in elderly patients with HR+, HER2− advanced breast cancer. 668 postmenopausal women with HR+, HER2− advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021); 295 patients were aged ≥ 65 years. Patients were randomized to ribociclib (600 mg/day; 3-weeks-on/1-week-off) plus letrozole (2.5 mg/day) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was PFS, which was evaluated in elderly (≥ 65 years) and younger (< 65 years) patients. Secondary endpoints included response rates and safety. Ribociclib plus letrozole significantly improved PFS vs placebo plus letrozole in elderly (hazard ratio: 0.608; 95% CI 0.394–0.937) and younger patients (hazard ratio: 0.523; 95% CI 0.378–0.723). Overall response rates were numerically higher in the ribociclib vs placebo arm, regardless of age. Ribociclib plus letrozole was well tolerated in elderly patients, with the safety profile similar to the overall study population. Nausea, vomiting, alopecia, and diarrhea were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm in both subgroups; most events were grade 1/2. In elderly patients, grade 1/2 anemia and fatigue were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm and discontinuation rates were similar in both arms. Addition of ribociclib to letrozole is a valid therapeutic option for elderly patients with HR+, HER2− advanced breast cancer in the first-line setting.
Tài liệu tham khảo
Howlader N, Noone A, Krapcho M et al (2016) SEER cancer statistics review, 1975–2013. National Cancer Institute. http://seer.cancer.gov/csr/1975_2013/. Accessed 24 Aug 2017
Howlader N, Altekruse S, Li C, Chen V, Clarke C, Ries L (2014) US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst 106:dju055
Riseberg D (2015) Treating elderly patients with hormone receptor-positive advanced breast cancer. Clin Med Insights Oncol 9:65–73
Rugo H, Rumble R, Macrae E et al (2016) Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology guideline. J Clin Oncol 34:3069–3103
Cardoso F, Costa A, Senkus E et al (2016) 3rd ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 3). Ann Oncol 28:16–33
Cardoso F, Costa A, Senkus E et al (2017) 3rd ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 3). Breast 31:244–259
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Breast Cancer, version 2.2017. http://www.nccn.org. Accessed 24 Aug 2017
Spano J, Falandry C, Chaibi P, Freyer G (2011) Current targeted therapies in breast cancer: clinical applications in the elderly woman. Oncologist 16:1144–1153
Owusu C, Berger N (2014) Comprehensive geriatric assessment in the older cancer patient: coming of age in clinical cancer care. Clin Pract (Lond) 11:749–762
Pritchard K, Burris HA 3rd, Ito Y et al (2013) Safety and efficacy of everolimus with exemestane vs. exemestane alone in elderly patients with HER2-negative, hormone receptor-positive breast cancer in BOLERO-2. Clin Breast Cancer 13:421–432
Tesarova P (2013) Breast cancer in the elderly-should it be treated differently? Rep Pract Oncol Radiother 18:26–33
Balducci L, Goetz-Parten D, Steinman M (2013) Polypharmacy and the management of the older cancer patient. Ann Oncol 23(Suppl 7):vii36–vii40
Hortobagyi G, Stemmer S, Burris H et al (2016) Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med 375:1738–1748
Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247
Oken MM, Creech RH, Tormey DC et al (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649–655
National Cancer Institute. Cancer Therapy Evaluation Program. Common Terminology Criteria for Adverse Events (CTCAE) v4.0. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Accessed 1 June 2017
World Health Organization. Health statistics and information systems. Proposed working definition of an older person in Africa for the MDS Project. http://www.who.int/healthinfo/survey/ageingdefnolder/en/. Accessed 10 Aug 2017
Thangavel C, Dean JL, Ertel A et al (2011) Therapeutically activating RB: reestablishing cell cycle control in endocrine therapy-resistant breast cancer. Endocr Relat Cancer 18:333–345
O’Brien N, Di Tomaso E, Ayala R et al (2014) In vivo efficacy of combined targeting of CDK4/6, ER and PI3K signaling in ER+ breast cancer. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research: Abstract 4756
Parasuraman S, Caponigro G, Loo A et al (2014) LEE011, a potent and selective CDK4/6 inhibitor, under preclinical and clinical investigation. Targ Anticancer Ther Congress: Oral Present O4:4
Finn RS, Dering J, Conklin D 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:R77
Rugo HS, Vidula N, Ma C (2016) Improving response to hormone therapy in breast cancer: new targets, new therapeutic options. Am Soc Clin Oncol Educ Book 35:e40–e54
Finn RS, Martin M, Rugo HS et al (2016) Palbociclib and letrozole in advanced breast cancer. N Engl J Med 375:1925–1936
Sherr CJ, Beach D, Shapiro GI (2015) Targeting CDK4 and CDK6: from discovery to therapy. Cancer Discov 6:353–367
Asghar U, Witkiewicz AK, Turner NC, Knudsen ES (2015) The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat Rev Drug Discov 14:130–146
Balducci L, Hardy C, Lyman C (2000) Hemopoietic reserve in the older cancer patient: clinical and economical considerations. Cancer Control 7:539–547
Cristofanilli M, Turner NC, Bondarenko I 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 2 randomised controlled trial. Lancet Oncol 17:425–439
Yancik R, Ries L, Yates J (1989) Breast cancer in aging women. A population-based study of contrasts in stage, surgery, and survival. Cancer 63:976–981
McGuire A, Brown J, Malone C et al (2015) Effects of age on the detection and management of breast cancer. Cancers (Basel) 7:908–929
Tran B, Bedard P (2011) Luminal-B breast cancer and novel therapeutic targets. Breast Cancer Res 13:221
Andre F, Stemmer S, Campone M et al (2017) Ribociclib + letrozole for first-line treatment of HR+, HER2− advanced breast cancer: efficacy by baseline tumor markers. In: AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics: Abstract CT045
Finn R, Jiang Y, Rugo H et al (2016) Biomarker analyses from the phase 3 PALOMA-2 trial of palbociclib (P) with letrozole (L) compared with placebo (PLB) plus L in postmenopausal women with ER+/HER2− advanced breast cancer (ABC). Ann Oncol 276:1–36
López-Pousa A, Rifà J, Casas de Tejerina A et al (2010) Risk assessment model for first-cycle chemotherapy-induced neutropenia in patients with solid tumors. Eur J Cancer Care 19:648–655
Lustberg M (2014) Management of neutropenia in cancer patients. Clin Adv Hematol Oncol 10:825–826
Rao A, Cohen H (2004) Symptom management in the elderly cancer patient: fatigue, pain, and depression. J Natl Cancer Inst Monogr 32:150–157
Patel K (2008) Epidemiology of anemia in older adults. Semin Hematol 45:210–217