HR+/HER2− metastatik meme kanserinde CDK4/6 inhibitörü alan hastalarda hematolojik ve biyokimyasal parametreler, tedaviye bağlı toksisite ve sağkalım ilişkisi: Retrospektif tek merkezli analiz
Öz
Amaç: CDK4/6 inhibitörleri, hormon reseptörü pozitif/HER2 negatif (HR+/HER2−) metastatik meme kanseri tedavisinde endokrin tedavi ile birlikte standart yaklaşım haline gelmiştir ve özellikle ribosiklib içeren çalışmalarda genel sağkalım avantajı net olarak gösterilmiştir. Bununla birlikte hematolojik ve biyokimyasal toksisiteler gerçek yaşam pratiğinde doz modifikasyonlarına yol açabilmektedir. Bu çalışmada, CDK4/6 inhibitörü alan hastalarda laboratuvar parametrelerinin toksisite ve sağkalım ile ilişkisi değerlendirilmiştir.
Gereç ve Yöntem: Analizler SPSS 26.0 programı kullanılarak %95 güven düzeyinde gerçekleştirilmiştir. Toksisite durumlarına göre kesme değerleri ROC analizi ile belirlenmiş; genel sağkalım (OS) ve progresyonsuz sağkalım (PFS) Kaplan–Meier ve Cox regresyon analizleri ile değerlendirilmiştir. Laboratuvar parametrelerinin zamana bağlı değişimleri tekrarlı ölçümler ANOVA testi ile analiz edilmiştir.
Bulgular: Tedavi sırasında gelişen nötropeni ve anemi açısından değerlendirilen başlangıç NLR, MCV, AST ve ALT parametrelerinde anlamlı ROC kesme değeri saptanmamıştır (p>0,05). Tedavi sırasında gelişen trombositopeni için AST (AUC 0,703; p=0,001) ve ALT (AUC 0,633; p=0,031) ayırt edici bulunmuştur. Yan etki nedeniyle doz azaltımı açısından AST sınırlı düzeyde anlamlıdır (AUC 0,615; p=0,029). Çok değişkenli Cox analizinde karaciğer metastazı varlığı OS için bağımsız kötü prognostik faktör olarak belirlenmiştir (HR 2,51; %95 GA: 1,14–5,53; p=0,022). Doz azaltımının OS ve PFS üzerine anlamlı etkisi gösterilememiştir.
Sonuç: Laboratuvar parametreleri bazı toksisiteleri öngörmede yararlı olabilirken, sağkalım açısından en güçlü belirleyiciler tümör biyolojisi ve metastatik yayılımı yansıtan klinik faktörlerdir. Doz azaltımının sağkalımı olumsuz etkilememesi, mevcut literatürle uyumludur.
Anahtar Kelimeler
CDK4/6 inhibitörü metastatik meme kanseri toksisite sağkalım
Etik Beyan
Bu çalışma Helsinki Bildirgesi ilkelerine uygun olarak yürütülmüş olup, Adana Şehir Eğitim ve Araştırma Hastanesi Etik Kurulu’nun 21 sayılı toplantısında alınan 995 karar numarası ile onaylanmıştır. Çalışmanın retrospektif tasarımı nedeniyle hastalardan ayrıca yazılı bilgilendirilmiş onam alınmamıştır.
Destekleyen Kurum
Bu çalışma için herhangi bir kurum, kuruluş ya da kişiden özel bir finansal destek alınmamıştır.
Kaynakça
- Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249. doi:10.3322/caac.21660. PMID: 33538338.
- Osborne CK, Schiff R. Mechanisms of endocrine resistance in breast cancer. Annu Rev Med. 2011;62:233–247. doi:10.1146/annurev-med-070909-182917. PMID: 20887199.
- O’Leary B, Finn RS, Turner NC. Treating cancer with selective CDK4/6 inhibitors. Nat Rev Clin Oncol. 2016;13(7):417–430. doi:10.1038/nrclinonc.2016.26. PMID: 27030077.
- Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016;375(20):1925–1936. doi:10.1056/NEJMoa1607303. PMID: 27959613.
- Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738–1748. doi:10.1056/NEJMoa1609709. PMID: 27717303.
- 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(32):3638–3646. doi:10.1200/JCO.2017.75.6155. PMID: 28968163.
- Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Overall survival with ribociclib plus letrozole in advanced breast cancer (MONALEESA-2). N Engl J Med. 2022;386(10):942–950. doi:10.1056/NEJMoa2114663. PMID: 35263501.
- Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, et al. Overall survival with ribociclib plus fulvestrant in advanced breast cancer (MONALEESA-3). N Engl J Med. 2020;382(6):514–524. doi:10.1056/NEJMoa1911149. PMID: 32053212.
- Tripathy D, Im SA, Colleoni M, Franke F, Bardia A, Harbeck N, et al. Ribociclib plus endocrine therapy for premenopausal women with HR-positive advanced breast cancer (MONALEESA-7). N Engl J Med. 2018;379(7):587–598. doi:10.1056/NEJMoa1808083. PMID: 30044998.
- Slamon DJ, Fasching PA, Patel R, Verma S, Hu C, Chia S, et al. Overall survival with palbociclib plus letrozole in advanced breast cancer (PALOMA-2). J Clin Oncol. 2024;42(5):417–428. doi:10.1200/JCO.23.00494. PMID: 38329938.
- Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, et al. MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR-positive, HER2-negative advanced breast cancer. J Clin Oncol. 2017;35(25):2875–2884. doi:10.1200/JCO.2017.73.7585. PMID: 28580882.
- Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, et al. Palbociclib in hormone-receptor–positive advanced breast cancer. N Engl J Med. 2015;373(3):209–219. PMID: 26030518.
- Low JL, Lim E, Bharwani L, Wong A, Wong K, Ow S, et al. Real-world outcomes from use of CDK4/6 inhibitors in the management of advanced/metastatic breast cancer. Ther Adv Med Oncol. 2022;14:17588359221139678. doi:10.1177/17588359221139678. PMID: 36570409.
- Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, 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). N Engl J Med. 2016;375(20):1925–1936. doi:10.1056/NEJMoa1607303. PMID: 2795961
- Queiroz MM, Sacardo KP, Ribeiro MF, Gadotti LL, Saddi R, de Carvalho Oliveira LJ, et al. Real-world treatment outcomes in HR+/HER2− metastatic breast cancer patients treated with CDK4/6 inhibitors. Cancer Treat Res Commun. 2023;35:100683. doi:10.1016/j.ctarc.2023.100683. PMID: 36716534.
- Rugo HS, Dieras V, Gelmon KA, et al. Impact of palbociclib plus letrozole on patient-reported outcomes in advanced breast cancer: Results from real-world clinical practice. Breast Cancer Res Treat. 2019;174(3):719–729.doi:10.1007/s10549-018-05048-9 PMID: 30649504
- Spring LM, Wander SA, Zangardi ML, Bardia A. CDK4/6 inhibitors in breast cancer: current controversies and future directions. Curr Oncol Rep. 2019;21(3):25. doi:10.1007/s11912-019-0770-5.PMID: 30854643
- Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, et al. MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR-positive, HER2-negative advanced breast cancer. J Clin Oncol. 2017;35(25):2875–2884. doi:10.1200/JCO.2017.73.7585
- Onesti CE, Jerusalem G. CDK4/6 inhibitors in breast cancer: differences in toxicity profiles and impact on agent choice. Expert Rev Anticancer Ther. 2021;21(4):283–298. doi:10.1080/14737140.2021.1852934
- Giannini EG, Borro P, Botta F, Fumagalli A, Malfatti F, Testa E, et al. Platelet count/spleen diameter ratio: proposal and validation of a non-invasive parameter to predict portal hypertension. Gut. 2003;52(8):1200–1205. doi:10.1136/gut.52.8.1200
- Peck-Radosavljevic M. Thrombocytopenia in chronic liver disease. Liver Int. 2017;37(6):778–793. doi:10.1111/liv.13317
- Tripathy D, Im SA, Colleoni M, Franke F, Bardia A, Harbeck N, et al. Ribociclib plus endocrine therapy for premenopausal women with HR-positive, advanced breast cancer (MONALEESA-7). Lancet Oncol. 2018;19(7):904–915. doi:10.1016/S1470-2045(18)30292-4
- Spring LM, Zangardi ML, Moy B, Bardia A. Clinical management of potential toxicities of CDK4/6 inhibitors in breast cancer. Oncologist. 2017;22(9):1039–1048. doi:10.1634/theoncologist.2017-0142
- Lobbezoo DJA, van Kampen RJW, Voogd AC, Dercksen MW, van den Berkmortel FWPJ, Smilde TJ, et al. Prognosis of metastatic breast cancer: are there differences between patients with liver metastases and other metastatic sites? Br J Cancer. 2015;112(5):897–903. doi:10.1038/bjc.2015.31
- Kennecke H, Yerushalmi R, Woods R, Cheang MCU, Voduc D, Speers CH, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010;28(20):3271–3277. doi:10.1200/JCO.2009.25.9820
- Cardoso F, Senkus E, Costa A, Papadopoulos E, Aapro M, André F, et al. 4th ESO–ESMO international consensus guidelines for advanced breast cancer (ABC 4). Ann Oncol. 2018;29(8):1634–1657. doi:10.1093/annonc/mdy192. PMID: 29878017.
- Tarantino P, Hamilton E, Tolaney SM, Cortes J, Morganti S, Ferraro E, et al. HER2-low breast cancer: pathological and clinical landscape. J Clin Oncol. 2020;38(17):1951–1962. doi:10.1200/JCO.19.02488
- Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9–20. doi:10.1056/NEJMoa2203690. PMID: 35704336.
- Inwald EC, Klinkhammer-Schalke M, Hofstädter F, Zeman F, Koller M, Gerstenhauer M, et al. Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort. BMC Cancer. 2013;13:297. doi:10.1186/1471-2407-13-297
- Savage DG, Ogundipe A, Allen RH, Stabler SP, Lindenbaum J. Etiology and diagnostic evaluation of macrocytosis. Am J Med Sci. 2000;319(6):343-352. PMID: 10875288
- Kaferle J, Strzoda CE. Evaluation of macrocytosis. Am Fam Physician. 2009;79(3):203-208. PMID: 19202968
- Rugo HS, Huober J, García-Sáenz JA, Masuda N, Sohn J, Andre V, et al. Management of abemaciclib-associated adverse events in MONARCH 2 and MONARCH 3. Oncologist. 2021;26(1):e53–e65. doi:10.1002/onco.13563
- Verma S, Bartlett CH, Schnell P, DeMichele A, Loi S, Ro J, et al. Palbociclib in combination with letrozole as first-line treatment of ER+/HER2− advanced breast cancer: detailed safety analysis. Oncologist. 2016;21(10):1165–1175. doi:10.1634/theoncologist.2016-0097
- European Medicines Agency. Kisqali (ribociclib) summary of product characteristics. EMA. Updated safety section. PMID: Not applicable (regulatory reference).
- Slamon DJ, Fasching PA, Patel R, Verma S, Hu C, Chia S, et al. Overall survival with palbociclib plus letrozole in advanced breast cancer (PALOMA-2). J Clin Oncol. 2024;42(5):417–428. doi:10.1200/JCO.23.00494. PMID: 38329938.
- Spring LM, Bardia A, Modi S. Targeting the cyclin D–CDK4/6 pathway in breast cancer: clinical implications and future directions. Oncologist. 2020;25(2):e194–e206. doi:10.1634/theoncologist.2019-0425. PMID: 31694968.
Association of hematological and biochemical parameters with treatment-related toxicity and survival in patients with HR+/HER2− metastatic breast cancer receiving CDK4/6 inhibitors: A retrospective single-center analysis
Öz
Aim: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy have become the standard of care for patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2−) metastatic breast cancer, with a clear overall survival benefit, particularly demonstrated in ribociclib-based trials. However, hematological and biochemical toxicities observed in real-world practice may lead to dose modifications. This study aimed to evaluate the relationship between laboratory parameters, treatment-related toxicity, and survival outcomes in patients receiving CDK4/6 inhibitors.
Materials and Methods: Statistical analyses were performed using SPSS version 26.0 with a 95% confidence level. Cut-off values for laboratory parameters, based on toxicity status, were determined using receiver operating characteristic (ROC) analysis. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier and Cox proportional hazards regression models. Time-dependent changes in laboratory parameters were assessed using repeated-measures ANOVA.
Results: No significant ROC cut-off values were identified for baseline neutrophil-to-lymphocyte ratio (NLR), mean corpuscular volume (MCV), aspartate aminotransferase (AST), or alanine aminotransferase (ALT) in predicting treatment-related neutropenia or anemia (p > 0.05). In contrast, AST (AUC 0.703, p = 0.001) and ALT (AUC 0.633, p = 0.031) were predictive of the development of thrombocytopenia during treatment. AST showed limited significance in predicting dose reduction due to adverse events (AUC 0.615; p = 0.029). In multivariate Cox analysis, the presence of liver metastases was identified as an independent poor prognostic factor for OS (HR 2.51; 95% CI: 1.14–5.53; p = 0.022). Dose reduction had no significant impact on OS or PFS.
Conclusion: While certain laboratory parameters may be useful in predicting specific treatment-related toxicities, survival outcomes are primarily determined by clinical factors reflecting tumor biology and metastatic burden. The lack of a negative impact of dose reduction on survival is consistent with the existing literature.
Anahtar Kelimeler
CDK4/6 inhibitor Metastatic breast cancer Treatment-related toxicity Survival
Etik Beyan
This study was reviewed and approved by the Clinical Research Ethics Committee of Health Sciences University Adana City Training and Research Hospital. The study had a retrospective design, and patient data were anonymized and used in accordance with confidentiality principles. The study was conducted in compliance with the Declaration of Helsinki and relevant national and international ethical guidelines. Due to the retrospective nature of the study, written informed consent was not obtained.
Destekleyen Kurum
Clinical Research Ethics Committee of Health Sciences University Adana City Training and Research Hospital.
Kaynakça
- Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249. doi:10.3322/caac.21660. PMID: 33538338.
- Osborne CK, Schiff R. Mechanisms of endocrine resistance in breast cancer. Annu Rev Med. 2011;62:233–247. doi:10.1146/annurev-med-070909-182917. PMID: 20887199.
- O’Leary B, Finn RS, Turner NC. Treating cancer with selective CDK4/6 inhibitors. Nat Rev Clin Oncol. 2016;13(7):417–430. doi:10.1038/nrclinonc.2016.26. PMID: 27030077.
- Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016;375(20):1925–1936. doi:10.1056/NEJMoa1607303. PMID: 27959613.
- Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738–1748. doi:10.1056/NEJMoa1609709. PMID: 27717303.
- 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(32):3638–3646. doi:10.1200/JCO.2017.75.6155. PMID: 28968163.
- Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Overall survival with ribociclib plus letrozole in advanced breast cancer (MONALEESA-2). N Engl J Med. 2022;386(10):942–950. doi:10.1056/NEJMoa2114663. PMID: 35263501.
- Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, et al. Overall survival with ribociclib plus fulvestrant in advanced breast cancer (MONALEESA-3). N Engl J Med. 2020;382(6):514–524. doi:10.1056/NEJMoa1911149. PMID: 32053212.
- Tripathy D, Im SA, Colleoni M, Franke F, Bardia A, Harbeck N, et al. Ribociclib plus endocrine therapy for premenopausal women with HR-positive advanced breast cancer (MONALEESA-7). N Engl J Med. 2018;379(7):587–598. doi:10.1056/NEJMoa1808083. PMID: 30044998.
- Slamon DJ, Fasching PA, Patel R, Verma S, Hu C, Chia S, et al. Overall survival with palbociclib plus letrozole in advanced breast cancer (PALOMA-2). J Clin Oncol. 2024;42(5):417–428. doi:10.1200/JCO.23.00494. PMID: 38329938.
- Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, et al. MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR-positive, HER2-negative advanced breast cancer. J Clin Oncol. 2017;35(25):2875–2884. doi:10.1200/JCO.2017.73.7585. PMID: 28580882.
- Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, et al. Palbociclib in hormone-receptor–positive advanced breast cancer. N Engl J Med. 2015;373(3):209–219. PMID: 26030518.
- Low JL, Lim E, Bharwani L, Wong A, Wong K, Ow S, et al. Real-world outcomes from use of CDK4/6 inhibitors in the management of advanced/metastatic breast cancer. Ther Adv Med Oncol. 2022;14:17588359221139678. doi:10.1177/17588359221139678. PMID: 36570409.
- Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, 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). N Engl J Med. 2016;375(20):1925–1936. doi:10.1056/NEJMoa1607303. PMID: 2795961
- Queiroz MM, Sacardo KP, Ribeiro MF, Gadotti LL, Saddi R, de Carvalho Oliveira LJ, et al. Real-world treatment outcomes in HR+/HER2− metastatic breast cancer patients treated with CDK4/6 inhibitors. Cancer Treat Res Commun. 2023;35:100683. doi:10.1016/j.ctarc.2023.100683. PMID: 36716534.
- Rugo HS, Dieras V, Gelmon KA, et al. Impact of palbociclib plus letrozole on patient-reported outcomes in advanced breast cancer: Results from real-world clinical practice. Breast Cancer Res Treat. 2019;174(3):719–729.doi:10.1007/s10549-018-05048-9 PMID: 30649504
- Spring LM, Wander SA, Zangardi ML, Bardia A. CDK4/6 inhibitors in breast cancer: current controversies and future directions. Curr Oncol Rep. 2019;21(3):25. doi:10.1007/s11912-019-0770-5.PMID: 30854643
- Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, et al. MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR-positive, HER2-negative advanced breast cancer. J Clin Oncol. 2017;35(25):2875–2884. doi:10.1200/JCO.2017.73.7585
- Onesti CE, Jerusalem G. CDK4/6 inhibitors in breast cancer: differences in toxicity profiles and impact on agent choice. Expert Rev Anticancer Ther. 2021;21(4):283–298. doi:10.1080/14737140.2021.1852934
- Giannini EG, Borro P, Botta F, Fumagalli A, Malfatti F, Testa E, et al. Platelet count/spleen diameter ratio: proposal and validation of a non-invasive parameter to predict portal hypertension. Gut. 2003;52(8):1200–1205. doi:10.1136/gut.52.8.1200
- Peck-Radosavljevic M. Thrombocytopenia in chronic liver disease. Liver Int. 2017;37(6):778–793. doi:10.1111/liv.13317
- Tripathy D, Im SA, Colleoni M, Franke F, Bardia A, Harbeck N, et al. Ribociclib plus endocrine therapy for premenopausal women with HR-positive, advanced breast cancer (MONALEESA-7). Lancet Oncol. 2018;19(7):904–915. doi:10.1016/S1470-2045(18)30292-4
- Spring LM, Zangardi ML, Moy B, Bardia A. Clinical management of potential toxicities of CDK4/6 inhibitors in breast cancer. Oncologist. 2017;22(9):1039–1048. doi:10.1634/theoncologist.2017-0142
- Lobbezoo DJA, van Kampen RJW, Voogd AC, Dercksen MW, van den Berkmortel FWPJ, Smilde TJ, et al. Prognosis of metastatic breast cancer: are there differences between patients with liver metastases and other metastatic sites? Br J Cancer. 2015;112(5):897–903. doi:10.1038/bjc.2015.31
- Kennecke H, Yerushalmi R, Woods R, Cheang MCU, Voduc D, Speers CH, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010;28(20):3271–3277. doi:10.1200/JCO.2009.25.9820
- Cardoso F, Senkus E, Costa A, Papadopoulos E, Aapro M, André F, et al. 4th ESO–ESMO international consensus guidelines for advanced breast cancer (ABC 4). Ann Oncol. 2018;29(8):1634–1657. doi:10.1093/annonc/mdy192. PMID: 29878017.
- Tarantino P, Hamilton E, Tolaney SM, Cortes J, Morganti S, Ferraro E, et al. HER2-low breast cancer: pathological and clinical landscape. J Clin Oncol. 2020;38(17):1951–1962. doi:10.1200/JCO.19.02488
- Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9–20. doi:10.1056/NEJMoa2203690. PMID: 35704336.
- Inwald EC, Klinkhammer-Schalke M, Hofstädter F, Zeman F, Koller M, Gerstenhauer M, et al. Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort. BMC Cancer. 2013;13:297. doi:10.1186/1471-2407-13-297
- Savage DG, Ogundipe A, Allen RH, Stabler SP, Lindenbaum J. Etiology and diagnostic evaluation of macrocytosis. Am J Med Sci. 2000;319(6):343-352. PMID: 10875288
- Kaferle J, Strzoda CE. Evaluation of macrocytosis. Am Fam Physician. 2009;79(3):203-208. PMID: 19202968
- Rugo HS, Huober J, García-Sáenz JA, Masuda N, Sohn J, Andre V, et al. Management of abemaciclib-associated adverse events in MONARCH 2 and MONARCH 3. Oncologist. 2021;26(1):e53–e65. doi:10.1002/onco.13563
- Verma S, Bartlett CH, Schnell P, DeMichele A, Loi S, Ro J, et al. Palbociclib in combination with letrozole as first-line treatment of ER+/HER2− advanced breast cancer: detailed safety analysis. Oncologist. 2016;21(10):1165–1175. doi:10.1634/theoncologist.2016-0097
- European Medicines Agency. Kisqali (ribociclib) summary of product characteristics. EMA. Updated safety section. PMID: Not applicable (regulatory reference).
- Slamon DJ, Fasching PA, Patel R, Verma S, Hu C, Chia S, et al. Overall survival with palbociclib plus letrozole in advanced breast cancer (PALOMA-2). J Clin Oncol. 2024;42(5):417–428. doi:10.1200/JCO.23.00494. PMID: 38329938.
- Spring LM, Bardia A, Modi S. Targeting the cyclin D–CDK4/6 pathway in breast cancer: clinical implications and future directions. Oncologist. 2020;25(2):e194–e206. doi:10.1634/theoncologist.2019-0425. PMID: 31694968.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Klinik Onkoloji |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Gönderilme Tarihi | 7 Ocak 2026 |
| Kabul Tarihi | 28 Ocak 2026 |
| Yayımlanma Tarihi | 9 Mart 2026 |
| DOI | https://doi.org/10.19161/etd.1857649 |
| IZ | https://izlik.org/JA75YH85ZL |
| Yayımlandığı Sayı | Yıl 2026 Cilt: 65 Sayı: 1 |
Kaynak Göster
Ege Tıp Dergisi, makalelerin Atıf-Gayri Ticari-Aynı Lisansla Paylaş 4.0 Uluslararası (CC BY-NC-SA 4.0) lisansına uygun bir şekilde paylaşılmasına izin verir.