Skip to main content
Erschienen in: Breast Cancer Research and Treatment 3/2018

04.11.2017 | Review

Efficacy and safety in older patient subsets in studies of endocrine monotherapy versus combination therapy in patients with HR+/HER2− advanced breast cancer: a review

verfasst von: Rachel A. Freedman, Sara M. Tolaney

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Prospective information regarding the tolerability and efficacy of endocrine therapy (ET) alone and in combination with targeted agents in older patients in the metastatic setting is limited. This review summarizes available trial data in this population.

Methods

We searched PubMed for Phase 2 or 3 trials with age-stratified patient cohorts (≥ 65 vs. < 65 years in most studies) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer treated with ET ± targeted agents.

Results

We identified 19 studies reporting 10 clinical trials. Efficacy was similar in age-stratified subsets. There was a reduced disease progression risk for ET + everolimus, palbociclib, or ribociclib versus ET alone. In the first-line setting, median progression-free survival (mPFS) in older patients was 8.5, 26.2 months, and not reached with letrozole + temsirolimus, palbociclib, and ribociclib, respectively, and in younger patients was 9.0, 18.8 months, and not reached, respectively. In the second-line setting, older patients had mPFS of 6.8 and 9.9 months with everolimus + exemestane and palbociclib + fulvestrant, respectively, and younger patients had mPFS of 8.1 and 9.5 months, respectively. Tolerability was worse for combination therapy versus monotherapy. No age-related differences in discontinuations were observed for CDK4/6 inhibitors, although a higher rate of treatment discontinuation was observed for patients ≥ 70 years receiving everolimus + exemestane. Adverse event rates were similar in age-stratified subsets.

Conclusions

ET + CDK4/6 or mTOR inhibitors are likely safe and effective in older patients with HR+, HER2− advanced breast cancer.
Literatur
3.
Zurück zum Zitat Baselga J, Campone M, Piccart M, Burris HA III, Rugo HS, Sahmoud T et al (2012) Everolimus in postmenopausal hormone-receptor–positive advanced breast cancer. N Engl J Med 366(6):520–529CrossRefPubMed Baselga J, Campone M, Piccart M, Burris HA III, Rugo HS, Sahmoud T et al (2012) Everolimus in postmenopausal hormone-receptor–positive advanced breast cancer. N Engl J Med 366(6):520–529CrossRefPubMed
6.
Zurück zum Zitat 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 35(25):2875–2884CrossRefPubMed 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 35(25):2875–2884CrossRefPubMed
8.
Zurück zum Zitat Aapro MS, Köhne C-H, Cohen HJ, Extermann M (2005) Never too old? Age should not be a barrier to enrollment in cancer clinical trials. Oncologist 10(3):198–204CrossRefPubMed Aapro MS, Köhne C-H, Cohen HJ, Extermann M (2005) Never too old? Age should not be a barrier to enrollment in cancer clinical trials. Oncologist 10(3):198–204CrossRefPubMed
9.
Zurück zum Zitat Freedman RA, Foster JC, Seisler DK, Lafky JM, Muss HB, Cohen HJ et al (2016) Accrual of older patients with breast cancer to alliance systemic therapy trials over time: protocol A151527. J Clin Oncol 35(4):421–431CrossRefPubMedPubMedCentral Freedman RA, Foster JC, Seisler DK, Lafky JM, Muss HB, Cohen HJ et al (2016) Accrual of older patients with breast cancer to alliance systemic therapy trials over time: protocol A151527. J Clin Oncol 35(4):421–431CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, 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(4):425–439. https://doi.org/10.1016/S1470-2045(15)00613-0 CrossRefPubMed Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, 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(4):425–439. https://​doi.​org/​10.​1016/​S1470-2045(15)00613-0 CrossRefPubMed
12.
13.
Zurück zum Zitat Hart LL, Souami F, Sutradhar S, Miller M, Germa C, Burris HA (2017) Efficacy and safety of ribociclib (LEE011) + letrozole in elderly patients with hormone receptor–positive, HER2-Negative advanced breast cancer in MONALEESA-2 study. Poster presented at the 34th Annual Miami Breast Cancer Conference, Miami Beach, FL, March 9–12 Hart LL, Souami F, Sutradhar S, Miller M, Germa C, Burris HA (2017) Efficacy and safety of ribociclib (LEE011) + letrozole in elderly patients with hormone receptor–positive, HER2-Negative advanced breast cancer in MONALEESA-2 study. Poster presented at the 34th Annual Miami Breast Cancer Conference, Miami Beach, FL, March 9–12
14.
Zurück zum Zitat Johnston SR, Kilburn LS, Ellis P, Dodwell D, Cameron D, Hayward L et al (2013) Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial. Lancet Oncol 14(10):989–998. https://doi.org/10.1016/S1470-2045(13)70322-X CrossRefPubMed Johnston SR, Kilburn LS, Ellis P, Dodwell D, Cameron D, Hayward L et al (2013) Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial. Lancet Oncol 14(10):989–998. https://​doi.​org/​10.​1016/​S1470-2045(13)70322-X CrossRefPubMed
18.
Zurück zum Zitat Rugo HS, Turner NC, Finn RS, Joy AA, Verma S, Harbeck N et al (2016) Palbociclib in combination with endocrine therapy in treatment-naive and previously treated elderly women with HR+, HER2− advanced breast cancer: a pooled analysis from randomized phase 2 and 3 studies. Poster presented at the 2016 San Antonio Breast Cancer Symposium, San Antonio, TX, December 6–10 Rugo HS, Turner NC, Finn RS, Joy AA, Verma S, Harbeck N et al (2016) Palbociclib in combination with endocrine therapy in treatment-naive and previously treated elderly women with HR+, HER2− advanced breast cancer: a pooled analysis from randomized phase 2 and 3 studies. Poster presented at the 2016 San Antonio Breast Cancer Symposium, San Antonio, TX, December 6–10
19.
Zurück zum Zitat Sonke GS, Hart LL, Campone M, Erdkamp F, Janni W, Verma S et al (2017) Efficacy and safety of ribociclib + letrozole in elderly patients with HR+, HER2- advanced breast cancer in MONALEESA-2. Paper presented at the European Cancer Congress, Amsterdam, The Netherlands, January 27–30 Sonke GS, Hart LL, Campone M, Erdkamp F, Janni W, Verma S et al (2017) Efficacy and safety of ribociclib + letrozole in elderly patients with HR+, HER2- advanced breast cancer in MONALEESA-2. Paper presented at the European Cancer Congress, Amsterdam, The Netherlands, January 27–30
21.
23.
Zurück zum Zitat Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S et al (2017) Updated results from MONALEESA-2, a phase 3 trial of first-line ribociclib + letrozole in hormone receptor-positive (HR+), HER2-negative (HER2−), advanced breast cancer (ABC). J Clin Oncol 35:1038 Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S et al (2017) Updated results from MONALEESA-2, a phase 3 trial of first-line ribociclib + letrozole in hormone receptor-positive (HR+), HER2-negative (HER2−), advanced breast cancer (ABC). J Clin Oncol 35:1038
24.
Zurück zum Zitat Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA (2009) Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol 27(17):2758–2765CrossRefPubMed Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA (2009) Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol 27(17):2758–2765CrossRefPubMed
25.
Zurück zum Zitat Braithwaite D, Satariano WA, Sternfeld B, Hiatt RA, Ganz PA, Kerlikowske K et al (2010) Long-term prognostic role of functional limitations among women with breast cancer. J Natl Cancer Inst 102(19):1468–1477CrossRefPubMedPubMedCentral Braithwaite D, Satariano WA, Sternfeld B, Hiatt RA, Ganz PA, Kerlikowske K et al (2010) Long-term prognostic role of functional limitations among women with breast cancer. J Natl Cancer Inst 102(19):1468–1477CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Land L, Dalton S, Jensen M, Ewertz M (2012) Influence of comorbidity on the effect of adjuvant treatment and age in patients with early-stage breast cancer. Br J Cancer 107(11):1901–1907CrossRefPubMedPubMedCentral Land L, Dalton S, Jensen M, Ewertz M (2012) Influence of comorbidity on the effect of adjuvant treatment and age in patients with early-stage breast cancer. Br J Cancer 107(11):1901–1907CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Hurria A, Dale W, Mooney M, Rowland JH, Ballman KV, Cohen HJ et al (2014) Designing therapeutic clinical trials for older and frail adults with cancer: U13 conference recommendations. J Clin Oncol 32(24):2587–2594CrossRefPubMedPubMedCentral Hurria A, Dale W, Mooney M, Rowland JH, Ballman KV, Cohen HJ et al (2014) Designing therapeutic clinical trials for older and frail adults with cancer: U13 conference recommendations. J Clin Oncol 32(24):2587–2594CrossRefPubMedPubMedCentral
Metadaten
Titel
Efficacy and safety in older patient subsets in studies of endocrine monotherapy versus combination therapy in patients with HR+/HER2− advanced breast cancer: a review
verfasst von
Rachel A. Freedman
Sara M. Tolaney
Publikationsdatum
04.11.2017
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 3/2018
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-017-4560-6

Weitere Artikel der Ausgabe 3/2018

Breast Cancer Research and Treatment 3/2018 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.