Impact of age and comorbidities on real-world outcomes in advanced breast cancer patients treated with palbociclib in first line: a nation-wide Danish retrospective study
DOI:
https://doi.org/10.2340/1651-226X.2025.43226Keywords:
Advanced Breast Cancer, Palbociclib, CDK4/6 inhibitor, survival, age, comorbidityAbstract
Background and purpose: Palbociclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, combined with aromatase inhibitors (AI), can be used in first-line treatment for estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) normal advanced breast cancer (ABC). This study aims to assess the impact of age and comorbidities on the progression-free survival (PFS) and overall survival (OS) of patients treated with palbociclib and AI.
Materials and methods: This nationwide, retrospective cohort study included 604 women with ER positive, HER2 normal ABC treated with palbociclib and an AI between 2017 and 2021. Data were obtained from the Danish Breast Cancer Group database. Survival outcomes were analyzed based on age, Charlson Comorbidity Index (CCI), number of comorbidities, and comorbidity type. PFS and OS were estimated using the Kaplan–Meier method.
Results: Median PFS for all patients was 30.6 months (95% confidence interval [CI], 27.4–34.2), and median OS was 55.6 months (95% CI, 51.8–58.9). Patients aged 65–75 years had significantly longer PFS and OS (p = 0.031 and p = 0.012) than patients aged under 65 and over 75 years. Visceral metastases were associated with shorter PFS and OS (p = 0.005). Comorbidity burden, including CCI score and comorbidity type, did not significantly affect survival outcomes.
Interpretation: In our data set, univariate analyses suggest age and visceral metastases to be potential factors influencing outcomes in patients with ABC treated with palbociclib plus an AI. Comorbidities, did not significantly impact survival, suggesting that palbociclib is well-tolerated in patients with varying health profiles.
ClinicalTrials.gov ID: NCT06307457.
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References
Sledge GWJ, Toi M, Neven P, Sohn J, Inoue K, Pivot X, et al. 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. 2017;35:2875–84.
https://doi.org/10.1200/JCO.2017.73.7585 DOI: https://doi.org/10.1200/JCO.2017.73.7585
Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35:3638–46.
https://doi.org/10.1200/JCO.2017.75.6155 DOI: https://doi.org/10.1200/JCO.2017.75.6155
Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im S-A, Masuda N, 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, PHA. Lancet Oncol. 2016;17:425–39.
https://doi.org/10.1016/S1470-2045(15)00613-0 DOI: https://doi.org/10.1016/S1470-2045(15)00613-0
Finn RS, Martin M, Rugo HS, Jones S, Im S-A, Gelmon K, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016;375:1925–36.
https://doi.org/10.1056/NEJMoa1607303 DOI: https://doi.org/10.1056/NEJMoa1607303
Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. 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. Ann Oncol. 2018;29:1541–7.
https://doi.org/10.1093/annonc/mdy155 DOI: https://doi.org/10.1093/annonc/mdy155
Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im S-A, et al. Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J Clin Oncol. 2018;36:2465–72.
https://doi.org/10.1200/JCO.2018.78.9909 DOI: https://doi.org/10.1200/JCO.2018.78.9909
El Badri S, Tahir B, Balachandran K, Bezecny P, Britton F, Davies M, et al. Palbociclib in combination with aromatase inhibitors in patients ≥ 75 years with oestrogen receptor-positive, human epidermal growth factor receptor 2 negative advanced breast cancer: a real-world multicentre UK study. Breast. 2021;60:199–205.
https://doi.org/10.1016/j.breast.2021.10.010 DOI: https://doi.org/10.1016/j.breast.2021.10.010
Goyal RK, Chen H, Abughosh SM, Holmes HM, Candrilli SD, Johnson ML. Overall survival associated with CDK4/6 inhibitors in patients with HR+/HER2- metastatic breast cancer in the United States: a SEER-Medicare population-based study. Cancer. 2023;129:1051–63.
https://doi.org/10.1002/cncr.34675 DOI: https://doi.org/10.1002/cncr.34675
Carola E, Pulido M, Falandry C, Paillaud E, Caillet P, Tassy L, et al. First-line systemic treatment with palbociclib in women aged ≥70 years presenting with hormone receptor-positive advanced breast cancer: results from the PALOMAGE program. J Clin Oncol. 2023;41:1018.
https://doi.org/10.1200/JCO.2023.41.16_suppl.1018 DOI: https://doi.org/10.1200/JCO.2023.41.16_suppl.1018
Brain E, Pulido M, Paillaud E, Grosjean J, Mina W, Caillet P, et al. Abstract P1-18-04: feasibility of palbociclib in women aged 70 and older with resistant and/or pretreated advanced breast cancer in the PALOMAGE study. Cancer Res. 2022;82:P1-18-04.
https://doi.org/10.1158/1538-7445.SABCS21-P1-18-04 DOI: https://doi.org/10.1158/1538-7445.SABCS21-P1-18-04
Caillet P, Pulido M, Brain E, Falandry C, Desmoulins I, Ghebriou D, et al. PALOMAGE, a French real-world cohort of elderly women beyond age 70 with advanced breast cancer receiving palbociclib: baseline characteristics and safety evaluation. J Clin Oncol. 2025;39:1012.
https://doi.org/10.1200/JCO.2021.39.15_suppl.1012 DOI: https://doi.org/10.1200/JCO.2021.39.15_suppl.1012
Rugo HS, Liu X, Li B, McRoy L, Layman RM, Brufsky A. Real-world comparative effectiveness of palbociclib plus letrozole versus letrozole in older patients with metastatic breast cancer. Breast. 2023;69:375–81.
https://doi.org/10.1016/j.breast.2023.03.015 DOI: https://doi.org/10.1016/j.breast.2023.03.015
Garly R, Berg T, Jensen M-B, Knoop A, Volmer L, Glavicic V, et al. A retrospective, non-interventional study of breast cancer patients diagnosed with ER+/HER2 negative, locally advanced or metastatic breast cancer treated with palbociclib in Denmark. Acta Oncol. 2023;62:290–7.
https://doi.org/10.1080/0284186X.2023.2194030 DOI: https://doi.org/10.1080/0284186X.2023.2194030
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–83.
https://doi.org/10.1016/0021-9681(87)90171-8 DOI: https://doi.org/10.1016/0021-9681(87)90171-8
Brain E, Chen C, Simon S, Pasupuleti V, Pfitzer KV, Gelmon KA. Palbociclib in older patients with advanced/metastatic breast cancer: a systematic review. Target Oncol. 2024;19:303–20.
https://doi.org/10.1007/s11523-024-01046-z DOI: https://doi.org/10.1007/s11523-024-01046-z
Brufsky A, Liu X, Li B, McRoy L, Chen C, Layman RM, et al. Real-world treatment patterns and effectiveness of palbociclib plus an aromatase inhibitor in patients with metastatic breast cancer aged 75 years or older. Front Oncol. 2023;13:1237751.
https://doi.org/10.3389/fonc.2023.1237751 DOI: https://doi.org/10.3389/fonc.2023.1237751
Cardoso F, Paluch-Shimon S, Schumacher-Wulf E, Matos L, Gelmon K, Aapro MS, et al. 6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7). Breast. 2024;76:103756.
https://doi.org/10.1016/j.breast.2024.103756 DOI: https://doi.org/10.1016/j.breast.2024.103756
Kapagan T, Bulut N, Erdem GU. Polypharmacy and drug-drug interactions in metastatic breast cancer patients receiving cyclin-dependent kinase (CDK) 4/6 inhibitors. J Oncol Pharm Pract. 2024;30:1403–10.
https://doi.org/10.1177/10781552231218959 DOI: https://doi.org/10.1177/10781552231218959
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Copyright (c) 2025 Alan Celik, Laurits Sebastian Dahl, Rasmus Garly, Vesna Glavicic, Maja Bendtsen Sharma, Sophie Yammeni, Humma Khan, Daniel Sloth Hauberg, Hanne Schultz Kapel, Ann Knoop, Tobias Berg
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