Hormon reseptör pozitif HER2-negatif metastatik meme kanseri tedavisinde üçüncü ve sonraki basamaklarda everolimus/eksemestan tedavisinin etkinliği ve toksisitesi

Year 2020, Volume: 4 Issue: 6, 443 - 446, 01.06.2020

Fatih Yıldız , Berna Öksüzoğlu

https://doi.org/10.28982/josam.745731

Cited By: 1

Abstract

Amaç: Siklin bağımlı kinaz 4-6 inhibitörü ve fulvestrant gibi tedavilerin tek başına ya da kombinasyon halinde kullanılmasının hormone reseptör (HR)-pozitif metastatik meme kanseri (MMK) tedavisinde daha etkin olduğunun gösterilmesiyle günlük pratikte everolimus/eksemestan tedavisi daha ileriki basamaklarda kullanılmaya başlamıştır. Bu çalışmanın amacı HR-pozitif HER2-negatif MMK tedavisinde üçüncü ve sonraki basamaklarda everolimus/eksemestan kombinasyon tedavisinin etkinliğini ve toksisitelerini gerçek yaşam verileri ile değerlendirmektir.
Yöntemler: Bu çalışma retrospektif kohort çalışmasıdır. Kasım 2013 - Mart 2020 tarihleri arasında merkezimizde HR-pozitif HER2-negatif MMK tanısıyla everolimus/eksemestan kombinasyon tedavisi alanlar çalışmaya dahil edilmiştir. Hastaların klinikopatolojik özellikleri ve tedavi ilişkili toksisiteler retrospektif olarak incelenmiştir.
Bulgular: Çalışmaya dahil edilen 33 hastanın ortanca yaşı 59’du (30-77). Hastaların 23’ünün (%69,7) visseral metastazı varken 10 (%30,3) hastanın yalnızca kemik metastazı vardı. Everolimus/eksemestan tedavisi 22 (%66,6) hastaya üçüncü basamakta, 11 (%33,3) hastaya ise sonraki basamaklarda verilmişti. Ortanca takip süresi 15.5 (0,3-35,5) aydı. Ortanca progresyonsuz sağkalım (PS) 7,0 (5,1-9,0, 95% CI) ay; ortanca genel sağkalım ise 21,3 (13,4-29,2, 95% CI) aydı. Yalnızca kemik metastazı olan hastalarla visseral metastazı olan hastalar arasında ortanca PS açısından fark yoktu (7,2–6,4 ay; P=0,96).
Sonuç: Everolimus/eksemestan kombinasyonu HR-pozitif HER2-negatif MMK tedavisinde ileriki basamaklarda da etkin ve tolere edilebilir bir tedavi seçeneğidir.

Keywords

Everolimus, Eksemestan, Meme kanseri

Efficacy and toxicity of everolimus plus exemestane in third and later lines treatment of hormone receptor-positive, HER2-negative metastatic breast cancer

Abstract

Aim: In daily practice, everolimus plus exemestane therapy has begun to be used in the later-lines as it has been demonstrated that treatments such as cyclin-dependent kinase (CDK) 4/6 inhibitors and fulvestrant, alone or in combination, are more effective in hormone receptor (HR)-positive metastatic breast cancer (MBC). The aim of this study is to evaluate the efficacy and toxicity of everolimus plus exemestane in the third line and later-lines on HR-positive Human Epidermal Growth Factor Receptor 2 (HER2)-negative MBC treatment with real-life data.
Methods: Patients who received everolimus plus exemestane with the diagnosis of HR-positive and HER2-negative MBC between November 2013 and March 2020 were included in this retrospective cohort study. Clinicopathological characteristics of patients and treatment related toxicities were evaluated retrospectively.
Results: The median age of the 33 patients included in the study was 59 (30-77) years. Twenty-three (69.7%) of the patients had visceral metastasis, while 10 (30.3%) had only bone metastasis. Everolimus plus exemestane was used in the third line in 22 (66.6%) patients and later-lines in 11 (33.3%) patients. The median follow-up time was 15.5 months (0.3-35.5). Median progression-free survival (PFS) and overall survival (OS) were 7.0 (5.1-9.0, 95% CI) months and 21.3 (13.4-29.2, 95% CI) months, respectively. Median PFS of patients with only bone metastasis and visceral metastasis were similar (7.2 vs 6.4 months, P=0.96).
Conclusion: Everolimus plus exemestane is an effective and tolerable treatment choice in the later-lines in the treatment of HR-positive HER2-negative MBC.

Keywords

Everolimus, Exemestane, Breast cancer

References

• 1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590. Epub 2020 Jan 8.
• 2. Fragomeni SM, Sciallis A, Jeruss JS. Molecular Subtypes and Local-Regional Control of Breast Cancer. Surg Oncol Clin N Am. 2018 Jan;27(1):95-120. doi: 10.1016/j.soc.2017.08.005. PMID: 29132568; PMCID: PMC5715810.
• 3. Perou CM, Sorlie T, Eisen MB,van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52.
• 4. Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10869-74. doi: 10.1073/pnas.191367098. PMID: 11553815; PMCID: PMC58566.
• 5. Spitale A, Mazzola P, Soldini D, Mazzucchelli L, Bordoni A. Breast cancer classification according to immunohistochemical markers: clinicopathologic features and short-term survival analysis in a population-based study from the South of Switzerland. Ann Oncol. 2009;20:628–35.
• 6. Tang P, Wang J, Bourne P. Molecular classifications of breast carcinoma with similar terminology and different definitions: are they the same? Hum Pathol. 2008;39:506–13.
• 7. Desmedt C, Sotiriou C, Piccart-Gebhart MJ. Development and validation of gene expression profile signatures in early-stage breast cancer. Cancer Invest. 2009;27:1–10.
• 8. Iwamoto T, Pusztai L. Predicting prognosis of breast cancer with gene signatures: are we lost in a sea of data? Genome Med. 2010;2:81.
• 9. Reis-Filho JS, Weigelt B, Fumagalli D, Sotiriou C. Molecular profiling: moving away from tumor philately. Sci Transl Med. 2010;2:47ps43.
• 10. Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. N Engl J Med. 2009;360:790–800.
• 11. Weigelt B, Baehner FL, Reis-Filho JS. The contribution of gene expression profiling to breast cancer classification, prognostication and prediction: a retrospective of the last decade. J Pathol. 2010;220:263–80.
• 12. Mungan İ, Dogru O, Aygen E, Dagli A. The relations of vascular endothelial growth factor–C and lymph node metastasis in breast cancer patients. J Surg Med. 2019;3(2):124-7.
• 13. Cole MP, Jones CT, Todd ID. A new anti-oestrogenic agent in late breast cancer. An early clinical appraisal of ICI 46474. Br J Cancer. 1971;25:270–5.
• 14. Jordan VC. Tamoxifen as the first targeted long-term adjuvant therapy for breast cancer. Endocr Relat Cancer. 2014 May 6;21(3):R235-46. doi: 10.1530/ERC-14-0092. PMID: 24659478; PMCID: PMC4029058.
• 15. Gao JJ, Cheng J, Bloomquist E, Sanchez J, Wedam SB, Singh H, et al. CDK4/6 inhibitor treatment for patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer: a US Food and Drug Administration pooled analysis. Lancet Oncol. 2020;21(2):250. Epub 2019 Dec 16.
• 16. AndréF, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, et al. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019;380(20):1929.
• 17. Beaver JA, Park BH. The BOLERO-2 trial: the addition of everolimus to exemestane in the treatment of postmenopausal hormone receptor-positive advanced breast cancer. Future Oncol. 2012 Jun;8(6):651-7. doi: 10.2217/fon.12.49. PMID: 22764762; PMCID: PMC3466807.
• 18. Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012 Feb 9;366(6):520-9. doi: 10.1056/NEJMoa1109653. Epub 2011 Dec 7. PMID: 22149876; PMCID: PMC5705195.
• 19. Royce M, Bachelot T, Villanueva C, Özgüroglu M, Azevedo SJ, Cruz FM, et al. Everolimus Plus Endocrine Therapy for Postmenopausal Women With Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: A Clinical Trial. JAMA Oncol. 2018 Jul 1;4(7):977-84. doi: 10.1001/jamaoncol.2018.0060. PMID: 29566104; PMCID: PMC5885212.
• 20. Jerusalem G, de Boer RH, Hurvitz S, Yardley DA, Kovalenko E, Ejlertsen B, et al. Everolimus Plus Exemestane vs Everolimus or Capecitabine Monotherapy for Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer: The BOLERO-6 Randomized Clinical Trial. JAMA Oncol. 2018 Oct 1;4(10):1367-74. doi: 10.1001/jamaoncol.2018.2262. PMID: 29862411; PMCID: PMC6233772.
• 21. O'Shaughnessy J, Thaddeus Beck J, Royce M. Everolimus-based combination therapies for HR+, HER2- metastatic breast cancer. Cancer Treat Rev. 2018 Sep;69:204-14. doi: 10.1016/j.ctrv.2018.07.013. Epub 2018 Jul 23.
• 22. Riccardi F, Colantuoni G, Diana A, Mocerino C, Cartenì G, Lauria R, et al. Exemestane and Everolimus combination treatment of hormone receptor positive, HER2 negative metastatic breast cancer: A retrospective study of 9 cancer centers in the Campania Region (Southern Italy) focused on activity, efficacy and safety. Mol Clin Oncol. 2018 Sep;9(3):255-63. doi: 10.3892/mco.2018.1672. Epub 2018 Jul 16. PMID: 30155246; PMCID: PMC6109668.
• 23. Moscetti L, Vici P, Gamucci T, Natoli C, Cortesi E, Marchetti P, et al. Safety analysis, association with response and previous treatments of everolimus and exemestane in 181 metastatic breast cancer patients: A multicenter Italian experience. Breast. 2016;29:96–101. doi: 10.1016/j.breast.2016.07.005.
• 24. 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): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016;17(4):425. Epub 2016 Mar 3.
• 25. 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+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. J Clin Oncol. 2017;35(25):2875. Epub 2017 Jun 3.
• 26. Yardley DA, Noguchi S, Pritchard KI, Burris HA 3rd, Baselga J, Gnant M, et al. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013 Oct;30(10):870-84. doi: 10.1007/s12325-013-0060-1. Epub 2013 Oct 25. Erratum in: Adv Ther. 2014 Sep;31(9):1008-9. PMID: 24158787; PMCID: PMC3898123.
• 27. Piccart M, Hortobagyi GN, Campone M, Pritchard KI, Lebrun F, Ito Y, et al. Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2†. Ann Oncol. 2014 Dec;25(12):2357-62. doi: 10.1093/annonc/mdu456. Epub 2014 Sep 17. PMID: 25231953; PMCID: PMC6267855.
• 28. Ciruelos E, Vidal M, Martínez de Dueñas E, Martínez-Jáñez N, Fernández Y, García-Sáenz JA, et al. Safety of everolimus plus exemestane in patients with hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer: results of phase IIIb BALLET trial in Spain. Clin Transl Oncol. 2018 Jun;20(6):753-60. doi: 10.1007/s12094-017-1784-1. Epub 2017 Nov 7. PMID: 29116433.