TY - JOUR
T1 - Overall Survival of CDK4/6-Inhibitor-Based Treatments in Clinically Relevant Subgroups of Metastatic Breast Cancer: Systematic Review and Meta-Analysis
T2 - Journal of the National Cancer Institute
AU - Schettini, F.
AU - Giudici, F.
AU - Giuliano, M.
AU - Cristofanilli, M.
AU - Arpino, G.
AU - Del Mastro, L.
AU - Puglisi, F.
AU - De Placido, S.
AU - Paris, I.
AU - De Placido, P.
AU - Venturini, S.
AU - De Laurentis, M.
AU - Conte, P.
AU - Juric, D.
AU - Llombart-Cussac, A.
AU - Pusztai, L.
AU - Prat, A.
AU - Jerusalem, G.
AU - Di Leo, A.
AU - Generali, D.
N1 - Cited By :4
Export Date: 18 February 2021
CODEN: JNCIA
Correspondence Address: Schettini, F.; Department of Clinical Medicine and Surgery, Via Sergio Pansini 5, Italy; email: schettini@clinic.cat
References: Schettini, F, Buono, G, Cardalesi, C, Desideri, I, De Placido, S, Del Mastro, L., Hormone receptor/human epidermal growth factor receptor 2-positive breast cancer: where we are now and where we are going (2016) Cancer Treat Rev, 46, pp. 20-26; Schettini, F, De Santo, I, Rea, CG, CDK 4/6 inhibitors as single agent in advanced solid tumors (2018) Front Oncol, 8, p. 608; Sledge, GW, Toi, M, Neven, P, MONARCH 2: abemaciclib in combination with fulvestrant in women with HRþ/HER2-advanced breast cancer who had progressed while receiving endocrine therapy (2017) J Clin Oncol, 35 (25), pp. 2875-2884; Cristofanilli, M, Turner, NC, Bondarenko, I, 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 (2016) Lancet Oncol, 17 (4), pp. 425-439; Tripathy, D, Im, S-A, Colleoni, M, Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial (2018) Lancet Oncol, 19 (7), pp. 904-915; Finn, RS, Martin, M, Rugo, HS, Palbociclib and letrozole in advanced breast cancer (2016) N Engl J Med, 375 (20), pp. 1925-1936; Hortobagyi, GN, Stemmer, SM, Burris, HA, Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer (2018) Ann Oncol, 29 (7), pp. 1541-1547; Slamon, DJ, Neven, P, Chia, S, Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3 (2018) J Clin Oncol, 36 (24), pp. 2465-2472; Goetz, MP, Toi, M, Campone, M, MONARCH 3: abemaciclib as initial therapy for advanced breast cancer (2017) J Clin Oncol, 35 (32), pp. 3638-3646; Giuliano, M, Schettini, F, Rognoni, C, Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network metaanalysis (2019) Lancet Oncol, 20 (10), pp. 1360-1369; Finn, RS, Crown, JP, Lang, I, 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 (2015) Lancet Oncol, 16 (1), pp. 25-35; Turner, NC, Slamon, DJ, Ro, J, Overall survival with palbociclib and fulvestrant in advanced breast cancer (2018) N Engl J Med, 379 (20), pp. 1926-1936; Miksad, RA, Zietemann, V, Gothe, R, Progression-free survival as a surrogate endpoint in advanced breast cancer (2008) Int J Technol Assess Health Care, 24, pp. 371-383. , (04); Forsythe, A, Chandiwana, D, Barth, J, Thabane, M, Baeck, J, Tremblay, G., Progression-free survival/time to progression as a potential surrogate for overall survival in HRþ, HER2 metastatic breast cancer (2018) Breast Cancer, 10, pp. 69-78; Sargent, DJ, Hayes, DF., Assessing the measure of a new drug: is survival the only thing that matters? 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Copenhagen, Denmark: The Nordic Cochrane Centre; Omarini, C, Piacentini, F, Sperduti, I, Endocrine-based targeted combination versus endocrine therapy alone as first-line treatment in elderly patients with hormone receptor-positive advanced breast cancer:meta-analysis of phase II and III randomized clinical trials (2019) J Clin Oncol, 37 (15), pp. 1046-1046. , (_suppl); Park, YH, Kim, T-Y, Kim, GM, Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): a multicentre, open-label, randomised, phase 2 trial (2019) Lancet Oncol, 20 (12), pp. 1750-1759; Rugo, HS, Rumble, RB, Macrae, E, Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology Guideline (2016) J Clin Oncol, 34 (25), pp. 3069-3103; Toss, A, Venturelli, M, Sperduti, I, First-line treatment for endocrinesensitive bone-only metastatic breast cancer: systematic review and metaanalysis (2019) Clin Breast Cancer, 19 (6), pp. 701-716; Gao, JJ, Cheng, J, Bloomquist, E, CDK4/6 inhibitor treatment for patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer: a US Food and Drug Administration pooled analysis (2020) Lancet Oncol, 21 (2), pp. 250-260; Wilson, FR, Varu, A, Mitra, D, Cameron, C, Iyer, S., Systematic review and network meta-analysis comparing palbociclib with chemotherapy agents for the treatment of postmenopausal women with HR-positive and HER2-negative advanced/metastatic breast cancer (2017) Breast Cancer Res Treat, 166 (1), pp. 167-177; Generali, D, Venturini, S, Rognoni, C, A network meta-analysis of everolimus plus exemestane versus chemotherapy in the first-and second-line treatment of estrogen receptor-positive metastatic breast cancer (2015) Breast Cancer Res Treat, 152 (1), pp. 95-117
PY - 2020
Y1 - 2020
N2 - Background: Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors + endocrine therapy (ET) prolonged progression-free survival as first- or second-line therapy for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer prognosis. Given the recent publication of overall survival (OS) data for the 3 CDK4/6-inhibitors, we performed a meta-analysis to identify a more precise and reliable benefit from such treatments in specific clinical subgroups. Methods: We conducted a systematic literature search to select all available phase II or III randomized clinical trials of CDK4/6-inhibitors + ET reporting OS data in first- or second-line therapy of HR+/HER2-negative pre- or postmenopausal metastatic breast cancer. A random effect model was applied for the analyses. Heterogeneity was assessed with I2statistic. Subgroup analysis was performed to explore the effect of study-level factors. The project was registered in the Open Science Framework database (doi: 10.17605/OSF.IO/TNZQP). Results: Six studies were included in our analyses (3421 patients). A clear OS benefit was observed in patients without (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.54 to 0.85, I2 = 0.0%) and with visceral involvement (HR = 0.76, 95% CI = 0.65 to 0.89, I2 = 0.0%), with at least 3 metastatic sites (HR = 0.75, 95% CI = 0.60 to 0.94, I2 = 11.6%), in an endocrine-resistant (HR = 0.79, 95% CI = 0.67 to 0.93, I2 = 0.0%) and sensitive subset (HR = 0.73, 95% CI = 0.61 to 0.88, I2 = 0.0%), for younger than 65 years (HR = 0.80, 95% CI = 0.67 to 0.95, I2 = 0.0%) and 65 years or older (HR = 0.71, 95% CI = 0.53 to 0.95, I2 = 44.4%), in postmenopausal (HR = 0.76, 95% CI = 0.67 to 0.86, I2 = 0.0%) and pre- or perimenopausal setting (HR = 0.76, 95% CI = 0.60 to 0.96, I2 = 0.0%) as well as in chemotherapy-naïve patients (HR = 0.72, 95% CI = 0.55 to 0.93, I2 = 0.0%). Conclusions: CDK4/6-inhibitors + ET combinations compared with ET alone improve OS independent of age, menopausal status, endocrine sensitiveness, and visceral involvement and should be preferred as upfront therapy instead of endocrine monotherapy. © 2020 The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
AB - Background: Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors + endocrine therapy (ET) prolonged progression-free survival as first- or second-line therapy for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer prognosis. Given the recent publication of overall survival (OS) data for the 3 CDK4/6-inhibitors, we performed a meta-analysis to identify a more precise and reliable benefit from such treatments in specific clinical subgroups. Methods: We conducted a systematic literature search to select all available phase II or III randomized clinical trials of CDK4/6-inhibitors + ET reporting OS data in first- or second-line therapy of HR+/HER2-negative pre- or postmenopausal metastatic breast cancer. A random effect model was applied for the analyses. Heterogeneity was assessed with I2statistic. Subgroup analysis was performed to explore the effect of study-level factors. The project was registered in the Open Science Framework database (doi: 10.17605/OSF.IO/TNZQP). Results: Six studies were included in our analyses (3421 patients). A clear OS benefit was observed in patients without (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.54 to 0.85, I2 = 0.0%) and with visceral involvement (HR = 0.76, 95% CI = 0.65 to 0.89, I2 = 0.0%), with at least 3 metastatic sites (HR = 0.75, 95% CI = 0.60 to 0.94, I2 = 11.6%), in an endocrine-resistant (HR = 0.79, 95% CI = 0.67 to 0.93, I2 = 0.0%) and sensitive subset (HR = 0.73, 95% CI = 0.61 to 0.88, I2 = 0.0%), for younger than 65 years (HR = 0.80, 95% CI = 0.67 to 0.95, I2 = 0.0%) and 65 years or older (HR = 0.71, 95% CI = 0.53 to 0.95, I2 = 44.4%), in postmenopausal (HR = 0.76, 95% CI = 0.67 to 0.86, I2 = 0.0%) and pre- or perimenopausal setting (HR = 0.76, 95% CI = 0.60 to 0.96, I2 = 0.0%) as well as in chemotherapy-naïve patients (HR = 0.72, 95% CI = 0.55 to 0.93, I2 = 0.0%). Conclusions: CDK4/6-inhibitors + ET combinations compared with ET alone improve OS independent of age, menopausal status, endocrine sensitiveness, and visceral involvement and should be preferred as upfront therapy instead of endocrine monotherapy. © 2020 The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
U2 - 10.1093/jnci/djaa071
DO - 10.1093/jnci/djaa071
M3 - Article
VL - 112
SP - 1089
EP - 1097
JO - J. Natl. Cancer Inst.
JF - J. Natl. Cancer Inst.
SN - 0027-8874
IS - 11
ER -