Comparison of palbociclib–letrozole and ribociclib–letrozole combinations as first-line treatment in metastatic HR+ / HER2- breast cancer
Öz
Aim: The aim of this study was to compare the efficacy and safety of palbociclib–letrozole and ribociclib–letrozole combinations as first-line treatment in patients with hormone receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer.
Materials and Methods: This retrospective study included 98 patients with HR positive and HER2 negative metastatic breast cancer who received palbociclib or ribociclib in combination with letrozole at Ege University Faculty of Medicine between January 1, 2018, and December 31, 2024. The median follow-up duration was 37,5 months. Progression-free survival, overall survival, objective response rate, and treatment-related toxicities were evaluated.
Results: The median progression-free survival in the entire cohort was 25,0 months. In the palbociclib group, the median progression-free survival was 25,0 months, while it was 27,0 months in the ribociclib group; the difference between the groups was not statistically significant (p = 0,064). The estimated 5-year overall survival rates were 50% in the palbociclib group and 52% in the ribociclib group, with no significant difference observed between the groups (p = 0,764). The objective response rate in the overall cohort was 70,4%, with no statistically significant difference between treatment arms. The most commonly reported toxicity in both groups was neutropenia, which was observed at a higher rate in the palbociclib group. In contrast, non-hematologic adverse events, particularly hepatotoxicity and rash, were more frequently observed in the ribociclib group.
Conclusion: Palbociclib and ribociclib combinations demonstrate similar efficacy and safety profiles as first-line treatments in patients with HR positive / HER2 negative metastatic breast cancer. Based on our real-world data, both regimens appear to be well tolerated. A personalized treatment approach, taking into account both efficacy and toxicity profiles, is recommended to guide clinical decision-making.
Anahtar Kelimeler
Palbociclib Ribociclib Real-world data Metastatic HR+ / HER2- breast cancer First-line treatment
Kaynakça
- Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2021;71(3):209-49.
- Giaquinto AN, Sung H, Miller KD, Kramer JL, Newman LA, Minihan A, et al. Breast cancer statistics, 2022. CA: a cancer journal for clinicians. 2022;72(6):524-41.
- DeSantis CE, Ma J, Gaudet MM, Newman LA, Miller KD, Goding Sauer A, et al. Breast cancer statistics, 2019. CA: a cancer journal for clinicians. 2019;69(6):438-51.
- Committee EG. Early breast cancer: ESMO Clinical Practice Guidelines: ESMO; 2023 [Available from: https://www.esmo.org/guidelines/guidelines-by-topic/breast-cancer/early-breast-cancer.
- Bertho M, Fraisse J, Patsouris A, Cottu P, Arnedos M, Pérol D, et al. Real-life prognosis of 5041 bone-only metastatic breast cancer patients in the multicenter national observational ESME program. Therapeutic Advances in Medical Oncology. 2021;13:1758835920987657.
- Lee SJ, Park S, Ahn HK, Yi JH, Cho EY, Sun JM, et al. Implications of bone-only metastases in breast cancer: favorable preference with excellent outcomes of hormone receptor positive breast cancer. Cancer research and treatment: official journal of Korean Cancer Association. 2011;43(2):89-95.
- Nardone A, De Angelis C, Trivedi MV, Osborne CK, Schiff R. The changing role of ER in endocrine resistance. The Breast. 2015;24:S60-S6.
- Ding L, Cao J, Lin W, Chen H, Xiong X, Ao H, et al. The roles of cyclin-dependent kinases in cell-cycle progression and therapeutic strategies in human breast cancer. International journal of molecular sciences. 2020;21(6):1960.
- Kasten MM, Giordano A. pRb and the cdks in apoptosis and the cell cycle. Cell Death & Differentiation. 1998;5(2):132-40.
- Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ, 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 Research. 2009;11:1-13.
- Reinert T, Barrios CH. Optimal management of hormone receptor positive metastatic breast cancer in 2016. Therapeutic advances in medical oncology. 2015;7(6):304-20.
- Finn RS, Martin M, Rugo HS, Jones S, Im S-A, Gelmon K, et al. Palbociclib and letrozole in advanced breast cancer. New England journal of medicine. 2016;375(20):1925-36.
- Rugo H, Finn R, Diéras V, Ettl J, Lipatov O, Joy A, et al. Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. Breast cancer research and treatment. 2019;174:719-29.
- Hortobagyi GN, Stemmer SM, Burris HA, Yap Y-S, Sonke GS, Paluch-Shimon S, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. New England journal of medicine. 2016;375(18):1738-48.
- Hortobagyi GN, Stemmer SM, Burris HA, Yap Y-S, 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. Annals of Oncology. 2018;29(7):1541-7.
- Johnston S, Martin M, Di Leo A, Im S-A, Awada A, Forrester T, et al. MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ breast cancer. 2019;5(1):5.
- Hortobagyi GN, Stemmer SM, Burris HA, Yap Y-S, Sonke GS, Hart L, et al. Overall survival with ribociclib plus letrozole in advanced breast cancer. New England Journal of Medicine. 2022;386(10):942-50.
- Goetz M, Masakazu T, Huober J, editors. MONARCH 3: final overall survival results of abemaciclib plus a nonsteroidal aromatase inhibitor as first-line therapy in patients with HR+, HER2-advanced breast cancer. San Antonio Breast Cancer Symposium; 2023.
- Finn RS, Rugo HS, Dieras VC, Harbeck N, Im S-A, Gelmon KA, et al. Overall survival (OS) with first-line palbociclib plus letrozole (PAL+ LET) versus placebo plus letrozole (PBO+ LET) in women with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (ER+/HER2− ABC): Analyses from PALOMA-2. American Society of Clinical Oncology; 2022.
- Abraham J, Coleman R, Elias A, Holmes FA, Kalinsky K, Kittaneh M, et al. Use of cyclin-dependent kinase (CDK) 4/6 inhibitors for hormone receptor-positive, human epidermal growth factor receptor 2-negative, metastatic breast cancer: a roundtable discussion by The Breast Cancer Therapy Expert Group (BCTEG). Breast cancer research and treatment. 2018;171:11-20.
- Thill M, Zahn MO, Welt A, Nusch A, Zaiss M, Engelken K, et al. Head‐to‐head comparison of palbociclib and ribociclib in first‐line treatment of HR‐positive/HER2‐negative metastatic breast cancer with real‐world data from the OPAL registry. International Journal of Cancer. 2025;156(9):1770-82.
- Tang H, De Souza K, Ahmad O, Shafiq T, Khan S, Anand A, et al. Palbociclib or Ribociclib with Aromatase Inhibitor in Post-menopausal Women with ER+/HER2–Advanced Breast Cancer? Real-world Overall Survival Evidence. Clinical Oncology. 2023;35(6):e420.
- Im S-A, Lu Y-S, Bardia A, Harbeck N, Colleoni M, Franke F, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer. New England journal of medicine. 2019;381(4):307-16.
- Yildirim HC, Kapar C, Koksal B, Seyyar M, Sanci PC, Guliyev M, et al. Efficacy of first-line CDK 4-6 inhibitors in premenopausal patients with metastatic breast cancer and the effect of dose reduction due to treatment-related neutropenia on efficacy: a Turkish Oncology Group (TOG) study. Journal of Chemotherapy. 2025;37(1):69-75.
- Yıldırım HÇ, Mutlu E, Chalabiyev E, Özen M, Keskinkılıç M, Ön S, et al. Clinical outcomes of cyclin-dependent kinase 4–6 (CDK 4–6) inhibitors in patients with male breast cancer: a multicenter study. The Breast. 2022;66:85-8.
- Kahraman S, Erul E, Seyyar M, Gumusay O, Bayram E, Demirel BC, et al. Treatment efficacy of ribociclib or palbociclib plus letrozole in hormone receptor-positive/HER2-negative metastatic breast cancer. Future Oncology. 2023;19(10):727-36.
Palbosiklib–letrozol ve ribosiklib–letrozol kombinasyonlarının metastatik HR+ / HER2- meme kanserinde birinci basamak tedavide etkinlik ve güvenlilik açısından karşılaştırılması
Öz
Amaç: Bu çalışmanın amacı, hormon reseptörü (HR) pozitif ve insan epidermal büyüme faktörü reseptörü 2 (HER2) negatif metastatik meme kanserli hastalarda, birinci basamak tedavi olarak kullanılan palbosiklib–letrozol ve ribosiklib–letrozol kombinasyonlarını etkinlik ve güvenlilik açısından karşılaştırmaktır.
Gereç ve Yöntem: Bu çalışma retrospektif olarak tasarlanmıştır. Çalışmaya, 1 Ocak 2018 ile 31 Aralık 2024 tarihleri arasında Ege Üniversitesi Tıp Fakültesi’nde HR pozitif / HER2 negatif metastatik meme kanseri tanısıyla palbosiklib veya ribosiklib ile birlikte letrozol tedavisi almış 98 hasta dahil edilmiştir. Medyan takip süresi 37,5 ay olup; progresyonsuz sağkalım, genel sağkalım, objektif yanıt oranı ve tedaviye bağlı toksisiteler değerlendirilmiştir.
Bulgular: Tüm kohortta medyan progresyonsuz sağkalım 25,0 ay olarak hesaplanmıştır. Palbosiklib grubunda medyan progresyonsuz sağkalım 25,0 ay, ribosiklib grubunda ise 27,0 ay olarak bulunmuştur; iki grup arasındaki fark istatistiksel olarak anlamlı değildir (p = 0,064). Beş yıllık tahmini genel sağkalım oranları palbosiklib ve ribosiklib gruplarında sırasıyla %50 ve %52 olarak hesaplanmıştır; gruplar arasında anlamlı fark izlenmemiştir (p = 0,764). Tüm kohortta objektif yanıt oranı %70,4 olarak bulunmuştur ve tedavi kolları arasında anlamlı fark saptanmamıştır. Her iki gurupta da en sık bildirilen toksisite nötropeni olup, palbosiklib grubunda daha yüksek oranda gözlenmiştir. Ribosiklib grubunda ise non-hematolojik yan etkiler, özellikle hepatotoksisite ve döküntü, daha sık izlenmiştir.
Sonuç: Palbosiklib ve ribosiklib kombinasyonları, HR pozitif / HER2 negatif metastatik meme kanserinde birinci basamak tedavide benzer etkinlik ve güvenlilik profili sergilemektedir. Gerçek yaşam verilerimize göre her iki tedavi de genel olarak iyi tolere edilmekte olup, klinik kararlarda etkinlik ve yan etki profili dikkate alınarak bireyselleştirilmiş bir tedavi yaklaşımının benimsenmesi önerilmektedir.
Anahtar Kelimeler
Palbosiklib Ribosiklib Gerçek yaşam verisi Metastatik HR +/ HER2- meme kanseri Birinci basamak tedavi
Kaynakça
- Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2021;71(3):209-49.
- Giaquinto AN, Sung H, Miller KD, Kramer JL, Newman LA, Minihan A, et al. Breast cancer statistics, 2022. CA: a cancer journal for clinicians. 2022;72(6):524-41.
- DeSantis CE, Ma J, Gaudet MM, Newman LA, Miller KD, Goding Sauer A, et al. Breast cancer statistics, 2019. CA: a cancer journal for clinicians. 2019;69(6):438-51.
- Committee EG. Early breast cancer: ESMO Clinical Practice Guidelines: ESMO; 2023 [Available from: https://www.esmo.org/guidelines/guidelines-by-topic/breast-cancer/early-breast-cancer.
- Bertho M, Fraisse J, Patsouris A, Cottu P, Arnedos M, Pérol D, et al. Real-life prognosis of 5041 bone-only metastatic breast cancer patients in the multicenter national observational ESME program. Therapeutic Advances in Medical Oncology. 2021;13:1758835920987657.
- Lee SJ, Park S, Ahn HK, Yi JH, Cho EY, Sun JM, et al. Implications of bone-only metastases in breast cancer: favorable preference with excellent outcomes of hormone receptor positive breast cancer. Cancer research and treatment: official journal of Korean Cancer Association. 2011;43(2):89-95.
- Nardone A, De Angelis C, Trivedi MV, Osborne CK, Schiff R. The changing role of ER in endocrine resistance. The Breast. 2015;24:S60-S6.
- Ding L, Cao J, Lin W, Chen H, Xiong X, Ao H, et al. The roles of cyclin-dependent kinases in cell-cycle progression and therapeutic strategies in human breast cancer. International journal of molecular sciences. 2020;21(6):1960.
- Kasten MM, Giordano A. pRb and the cdks in apoptosis and the cell cycle. Cell Death & Differentiation. 1998;5(2):132-40.
- Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ, 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 Research. 2009;11:1-13.
- Reinert T, Barrios CH. Optimal management of hormone receptor positive metastatic breast cancer in 2016. Therapeutic advances in medical oncology. 2015;7(6):304-20.
- Finn RS, Martin M, Rugo HS, Jones S, Im S-A, Gelmon K, et al. Palbociclib and letrozole in advanced breast cancer. New England journal of medicine. 2016;375(20):1925-36.
- Rugo H, Finn R, Diéras V, Ettl J, Lipatov O, Joy A, et al. Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. Breast cancer research and treatment. 2019;174:719-29.
- Hortobagyi GN, Stemmer SM, Burris HA, Yap Y-S, Sonke GS, Paluch-Shimon S, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. New England journal of medicine. 2016;375(18):1738-48.
- Hortobagyi GN, Stemmer SM, Burris HA, Yap Y-S, 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. Annals of Oncology. 2018;29(7):1541-7.
- Johnston S, Martin M, Di Leo A, Im S-A, Awada A, Forrester T, et al. MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ breast cancer. 2019;5(1):5.
- Hortobagyi GN, Stemmer SM, Burris HA, Yap Y-S, Sonke GS, Hart L, et al. Overall survival with ribociclib plus letrozole in advanced breast cancer. New England Journal of Medicine. 2022;386(10):942-50.
- Goetz M, Masakazu T, Huober J, editors. MONARCH 3: final overall survival results of abemaciclib plus a nonsteroidal aromatase inhibitor as first-line therapy in patients with HR+, HER2-advanced breast cancer. San Antonio Breast Cancer Symposium; 2023.
- Finn RS, Rugo HS, Dieras VC, Harbeck N, Im S-A, Gelmon KA, et al. Overall survival (OS) with first-line palbociclib plus letrozole (PAL+ LET) versus placebo plus letrozole (PBO+ LET) in women with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (ER+/HER2− ABC): Analyses from PALOMA-2. American Society of Clinical Oncology; 2022.
- Abraham J, Coleman R, Elias A, Holmes FA, Kalinsky K, Kittaneh M, et al. Use of cyclin-dependent kinase (CDK) 4/6 inhibitors for hormone receptor-positive, human epidermal growth factor receptor 2-negative, metastatic breast cancer: a roundtable discussion by The Breast Cancer Therapy Expert Group (BCTEG). Breast cancer research and treatment. 2018;171:11-20.
- Thill M, Zahn MO, Welt A, Nusch A, Zaiss M, Engelken K, et al. Head‐to‐head comparison of palbociclib and ribociclib in first‐line treatment of HR‐positive/HER2‐negative metastatic breast cancer with real‐world data from the OPAL registry. International Journal of Cancer. 2025;156(9):1770-82.
- Tang H, De Souza K, Ahmad O, Shafiq T, Khan S, Anand A, et al. Palbociclib or Ribociclib with Aromatase Inhibitor in Post-menopausal Women with ER+/HER2–Advanced Breast Cancer? Real-world Overall Survival Evidence. Clinical Oncology. 2023;35(6):e420.
- Im S-A, Lu Y-S, Bardia A, Harbeck N, Colleoni M, Franke F, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer. New England journal of medicine. 2019;381(4):307-16.
- Yildirim HC, Kapar C, Koksal B, Seyyar M, Sanci PC, Guliyev M, et al. Efficacy of first-line CDK 4-6 inhibitors in premenopausal patients with metastatic breast cancer and the effect of dose reduction due to treatment-related neutropenia on efficacy: a Turkish Oncology Group (TOG) study. Journal of Chemotherapy. 2025;37(1):69-75.
- Yıldırım HÇ, Mutlu E, Chalabiyev E, Özen M, Keskinkılıç M, Ön S, et al. Clinical outcomes of cyclin-dependent kinase 4–6 (CDK 4–6) inhibitors in patients with male breast cancer: a multicenter study. The Breast. 2022;66:85-8.
- Kahraman S, Erul E, Seyyar M, Gumusay O, Bayram E, Demirel BC, et al. Treatment efficacy of ribociclib or palbociclib plus letrozole in hormone receptor-positive/HER2-negative metastatic breast cancer. Future Oncology. 2023;19(10):727-36.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Klinik Onkoloji |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 8 Eylül 2025 |
| Gönderilme Tarihi | 22 Nisan 2025 |
| Kabul Tarihi | 13 Mayıs 2025 |
| Yayımlandığı Sayı | Yıl 2025 Cilt: 64 Sayı: 3 |
