Evaluation of Factors That Increase the Risk of Hepatotoxicity in Patients Using Palbociclib and Ribociclib
Abstract
Aim: In patients with hormone receptor-positive and HER2-negative metastatic breast cancer, the use of CDK 4/6 inhibitors in combination with endocrine therapy have become a standard of care.
Methods: This was a retrospective study involved patients over the age of 18 years, who had de novo metastatic or locally breast cancer progressed to the metastatic stage and were treated with ribociclib and/or palbociclib.
Results: The mean age of a total of 73 patients included in the study was 57.0±10.3 years. Thirty-four (46.6%) patients were treated with palbociclib, 35 (47.9%) patients with ribociclib, 4 (5.5%) with palbociclib and ribociclib. Twenty-five (34.2%) of the patients developed any grade of hepatotoxicity, 12 (16.4%) of them was grade 2 hepatotoxicity. Of these patients, 11 (44%) received palbociclib, 13 (52%) received ribociclib, and 1 (4%) received palbociclib and ribociclib. In patients who were treated with palbociclib, 1 (2.9%) developed grade 3 hepatotoxicity and 1 (2.9%) developed grade 4 hepatotoxicity. Of those who received ribociclib, 3 (8.5%)
developed grade 3 hepatotoxicity and 2 (5.7%) developed grade 4 hepatotoxicity.
Conclusions: In conclusion, it can be stated that ribociclib is more toxic to the liver than palbociclib, since patients who received ribociclib and developed grade 3-4 hepatotoxicity had no disease that facilitates hepatotoxicity. We believe that more comprehensive studies are needed to determine the factors that facilitate hepatotoxicity such as liver metastasis and to select the drug accordingly will prevent patients from being devoid of this group of drugs and discontinuing their treatment due to toxicity.
Keywords
References
- 1.Ferlay J, Colombet M, Soerjomataram I, et al. Cancer statistics for the year 2020: An overview. Int J Cancer. 2021; 149(4): 778-89. https://doi.org/10.1002/ijc.33588
- 2.Perez EA. Treatment strategies for advanced hormone receptor-positive and human epidermal growth factor 2-negative breast cancer: the role of treat¬ment order. Drug Resistance Updates. 2016; 24: 13-22. https://doi.org/10.1016/j.drup.2015.11.001
- 3.Ditsch N, Schmidt M. Treatment of Advanced Hormone Receptor-Positive (HR+) HER2-negative Breast Cancer. Geburtshilfe Frauenheilkd. 2019 Dec;79(12):1328-35. https://doi.org/10.1055/a-1037-5205
- 4.Kurebayashi J. Endocrine-resistant breast cancer: Underlying mecha-nisms and strategies for overcoming resistance. Breast Cancer. 2003; 10(2):112-9. https://doi.org/10.1007/BF02967635
- 5.Osborne CK, Schiff R. Mechanisms of Endocrine Resistance in Breast Cancer. Annu Rev Med. 2011; 62(1): 233-47. https://doi.org/10.1146/annurev-med-070909-182917
- 6.Turner NC, Slamon DJ, Ro J, et al. Overall Survival with Palbociclib and Ful¬vestrant in Advanced Breast Cancer. N Engl J Med. 20185; 379(20): 1926-36. https://doi.org/10.1056/NEJMoa1810527
- 7.Slamon DJ, Neven P, Chia S, et al. Ribociclib plus fulvestrant for post-meno¬pausal women with hormone receptor-positive, human epidermal growth fac¬tor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival. Annals of Oncology. 2021; 32(8): 1015-24. https://doi.org/10.1016/j.annonc.2021.05.353
- 8.Hortobagyi GN, Stemmer SM, Burris HA et al. Ribociclib as First-Line Ther¬apy for HR-Positive, Advanced Breast Cancer. N Engl J Med. 2016; 375(18): 1738-48. 9.Sledge GW, Toi M, Neven P, et al. MONARCH 2: Abemaciclib in Combina-tion with Fulvestrant in Women With HR+/HER2− Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. JCO. 2017; 35(25): 2875-84. https://doi.org/10.1200/JCO.2017.73.7585
- 10.Cardoso F, Senkus E, Costa A, et al. 4th ESO-ESMO International Con-sensus Guidelines for Advanced Breast Cancer (ABC 4). Annals of Oncol-ogy. 2018; 29(8): 1634-57. https://doi.org/10.1093/annonc/mdy192
- 11.Cortés J, Kim SB, Chung WP, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022; 386(12): 1143-54. https://doi.org/10.1056/NEJMoa2115022
- 12.Kellokumpu-Lehtinen P, Lantto A, Kokko R, et al. Paclitaxel-ifosfamide for anthracycline-resistant advanced breast cancer. Int J Clin Pharmacol Res. 2002; 22(2): 47-53.
- 13.Jones SE, Erban J, Overmoyer B, Budd GT, et al. Randomized Phase III Study of Docetaxel Compared with Paclitaxel in Metastatic Breast Cancer. JCO. 2005; 23(24): 5542-51. https://doi.org/10.1200/JCO.2005.02.027
- 14.Spring LM, Wander SA, Zangardi M, et al. CDK 4/6 Inhibitors in Breast Can¬cer: Current Controversies and Future Directions. Curr Oncol Rep. 2019; 21(3): 25. https://doi.org/10.1007/s11912-019-0769-3
- 15.LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Dis¬eases; 2012.
- 16.Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus pal-bociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that pro-gressed on previous endo¬crine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. The Lan-cet Oncology. 2016; 17(4): 425-39. https://doi.org/10.1016/S1470-2045(15)00613-0
- 17.Farhat F, Tarabaih M, Kanj A, et al. Palbociclib safety and efficacy be-yond Ribociclib-induced liver toxicity in metastatic hormone-receptors positive breast cancer patient. Anti-Cancer Drugs. 2020; 31(1): 85-9. https://doi.org/10.1097/CAD.0000000000000845
Evaluation of Factors That Increase the Risk of Hepatotoxicity in Patients Using Palbociclib and Ribociclib
Abstract
Background
In patients with hormone receptor-positive and HER2-negative metastatic breast cancer, the use of CDK 4/6 inhibitors in combination with endocrine therapy have become a standard of care.
Methods
This was a retrospective study involved patients over the age of 18 years, who had de novo metastatic or local-ly breast cancer progressed to the metastatic stage and were treated with ribociclib and/or palbociclib.
Results
The mean age of a total of 73 patients included in the study was 57.0±10.3 years. Thirty-four (46.6%) patients were treated with palbociclib, 35 (47.9%) patients with ribociclib, 4 (5.5%) with palbociclib and ribociclib. Twenty-five (34.2%) of the patients developed any grade of hepatotoxicity, 12 (16.4%) of them was grade 2 hepatotoxicity. Of these patients, 11 (44%) received palbociclib, 13 (52%) received ribociclib, and 1 (4%) received palbociclib and ribociclib. In patients who were treated with palbociclib, 1 (2.9%) developed grade 3 hepatotoxicity and 1 (2.9%) developed grade 4 hepatotoxicity. Of those who received ribociclib, 3 (8.5%) developed grade 3 hepatotoxicity and 2 (5.7%) developed grade 4 hepatotoxicity.
Conclusion
In conclusion, it can be stated that ribociclib is more toxic to the liver than palbociclib, since patients who received ribociclib and developed grade 3-4 hepatotoxicity had no disease that facilitates hepatotoxicity. We believe that more comprehensive studies are needed to determine the factors that facilitate hepatotoxicity such as liver metastasis and to select the drug accordingly will prevent patients from being devoid of this group of drugs and discontinuing their treatment due to toxicity.
References
- 1.Ferlay J, Colombet M, Soerjomataram I, et al. Cancer statistics for the year 2020: An overview. Int J Cancer. 2021; 149(4): 778-89. https://doi.org/10.1002/ijc.33588
- 2.Perez EA. Treatment strategies for advanced hormone receptor-positive and human epidermal growth factor 2-negative breast cancer: the role of treat¬ment order. Drug Resistance Updates. 2016; 24: 13-22. https://doi.org/10.1016/j.drup.2015.11.001
- 3.Ditsch N, Schmidt M. Treatment of Advanced Hormone Receptor-Positive (HR+) HER2-negative Breast Cancer. Geburtshilfe Frauenheilkd. 2019 Dec;79(12):1328-35. https://doi.org/10.1055/a-1037-5205
- 4.Kurebayashi J. Endocrine-resistant breast cancer: Underlying mecha-nisms and strategies for overcoming resistance. Breast Cancer. 2003; 10(2):112-9. https://doi.org/10.1007/BF02967635
- 5.Osborne CK, Schiff R. Mechanisms of Endocrine Resistance in Breast Cancer. Annu Rev Med. 2011; 62(1): 233-47. https://doi.org/10.1146/annurev-med-070909-182917
- 6.Turner NC, Slamon DJ, Ro J, et al. Overall Survival with Palbociclib and Ful¬vestrant in Advanced Breast Cancer. N Engl J Med. 20185; 379(20): 1926-36. https://doi.org/10.1056/NEJMoa1810527
- 7.Slamon DJ, Neven P, Chia S, et al. Ribociclib plus fulvestrant for post-meno¬pausal women with hormone receptor-positive, human epidermal growth fac¬tor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival. Annals of Oncology. 2021; 32(8): 1015-24. https://doi.org/10.1016/j.annonc.2021.05.353
- 8.Hortobagyi GN, Stemmer SM, Burris HA et al. Ribociclib as First-Line Ther¬apy for HR-Positive, Advanced Breast Cancer. N Engl J Med. 2016; 375(18): 1738-48. 9.Sledge GW, Toi M, Neven P, et al. MONARCH 2: Abemaciclib in Combina-tion with Fulvestrant in Women With HR+/HER2− Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. JCO. 2017; 35(25): 2875-84. https://doi.org/10.1200/JCO.2017.73.7585
- 10.Cardoso F, Senkus E, Costa A, et al. 4th ESO-ESMO International Con-sensus Guidelines for Advanced Breast Cancer (ABC 4). Annals of Oncol-ogy. 2018; 29(8): 1634-57. https://doi.org/10.1093/annonc/mdy192
- 11.Cortés J, Kim SB, Chung WP, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022; 386(12): 1143-54. https://doi.org/10.1056/NEJMoa2115022
- 12.Kellokumpu-Lehtinen P, Lantto A, Kokko R, et al. Paclitaxel-ifosfamide for anthracycline-resistant advanced breast cancer. Int J Clin Pharmacol Res. 2002; 22(2): 47-53.
- 13.Jones SE, Erban J, Overmoyer B, Budd GT, et al. Randomized Phase III Study of Docetaxel Compared with Paclitaxel in Metastatic Breast Cancer. JCO. 2005; 23(24): 5542-51. https://doi.org/10.1200/JCO.2005.02.027
- 14.Spring LM, Wander SA, Zangardi M, et al. CDK 4/6 Inhibitors in Breast Can¬cer: Current Controversies and Future Directions. Curr Oncol Rep. 2019; 21(3): 25. https://doi.org/10.1007/s11912-019-0769-3
- 15.LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Dis¬eases; 2012.
- 16.Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus pal-bociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that pro-gressed on previous endo¬crine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. The Lan-cet Oncology. 2016; 17(4): 425-39. https://doi.org/10.1016/S1470-2045(15)00613-0
- 17.Farhat F, Tarabaih M, Kanj A, et al. Palbociclib safety and efficacy be-yond Ribociclib-induced liver toxicity in metastatic hormone-receptors positive breast cancer patient. Anti-Cancer Drugs. 2020; 31(1): 85-9. https://doi.org/10.1097/CAD.0000000000000845
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences |
| Journal Section | Articles |
| Authors | |
| Publication Date | August 31, 2023 |
| Acceptance Date | May 30, 2023 |
| Published in Issue | Year 2023 Volume: 6 Issue: 2 |
