Pertuzumab-mediated Cardiotoxicity: A Single Center Study.

Year 2023, , 314 - 320, 30.06.2023

Aynur Acıbuca , Ayşenur Uçar , Ahmet Sümbül , Ahmet Sezer Şenol Demırcan , Haldun Müderrisoğlu , Özgür Özyilkan

https://doi.org/10.31832/smj.1163527

Abstract

Pertuzumab-mediated Cardiotoxicity: A Single Center Study.
Objective: Recent clinical trials have shown that adding pertuzumab to trastuzumab improved the cellular response to therapy and provides a survival benefit compared with trastuzumab alone. However, it has raised concerns about additive risk of cardiotoxicity. Real life data on pertuzumab-induced cardiotoxicity are limited.
Materials and Methods: Patients a diagnosis of breast cancer who had been treated trastuzumab plus pertuzumab between January 2017 and June 2022 and had undergone regularly transthoracic echocardiography, as a part of control visits, in our medical center were included. We performed descriptive statistical analysis to evaluate the patients’ characteristics and therapies, which could increase the risk of cardiac adverse events. Cardiotoxicity was evaluated by serial left ventricular ejection fraction (LVEF) measuring by 2D echocardiography at baseline and every three months during pertuzumab therapy and was defined as a decrease in LVEF > 10% to below 55%.
Results: There were 118 patients fulfilling the inclusion criteria. The median age of the population was 51 (41-60) years. The median duration of pertuzumab therapy was 15 (9–57) weeks. Pertuzumab therapy was discontinued in two patients because of an allergic reaction and in other two patients due to cardiotoxicity. The reduced LVEF did not recover to baseline values in either patient.
Conclusion: The incidence of cardiotoxicity (1.69%) in the current study was no higher than expected for trastuzumab alone. Data from previous studies and the results of this study support that pertuzumab causes no increase in cardiotoxicity. Still, large clinical trials are needed to verify the cardiac safety of pertuzumab in a real-world setting.

Keywords

breast cancer; cardiotoxicity; pertuzumab.

Supporting Institution

The authors did not receive support from any organization for the submitted work.

Thanks

None

Pertuzumab Aracılı Kardiyotoksisite: Tek Merkezli Bir Çalışma

Abstract

Amaç: Son klinik çalışmalar, trastuzumaba pertuzumab eklenmesinin tedaviye hücresel yanıtı iyileştirdiğini ve tek başına trastuzumab ile karşılaştırıldığında sağkalım avantajı sağladığını göstermiştir. Bununla birlikte, kardiyotoksisite riskini arttırabileceği konusunda endişe uyandırmıştır. Pertuzumabın neden olduğu kardiyotoksisiteye ilişkin gerçek yaşam verileri kısıtlıdır.
Gereç ve Yöntemler: Ocak 2017-Haziran 2022 tarihleri arasında trastuzumab beraberinde pertuzumab tedavisi gören ve kontrol vizitleri kapsamında düzenli olarak transtorasik ekokardiyografi çekilen hastalar çalışmaya dahil edildi. Kardiyak advers olay riskini arttırabilecek hasta özelliklerini ve tedavilerini değerlendirmek için tanımlayıcı istatistiksel analizler kullanıldı. Başlangıçta ve pertuzumab tedavisi sırasında her 3 ayda bir 2 boyutlu ekokardiyografi ile yapılan ardışık sol ventrikül ejeksiyon fraksiyonu (SoVEF) ölçümleri değerlendirildi ve SoVEF’nin %10’dan fazla düşüşle %55’in altına inmesi kardiyotoksisite olarak tanımlandı.
Bulgular: Dahil edilme kriterlerini karşılayan 118 hasta vardı. Populasyonun yaş ortancası 51 (41-60) yıldı. Pertuzumab tedavisinin ortanca süresi 15 (9-57) haftaydı. Pertuzumab tedavisi iki hastada alerjik reaksiyon, diğer iki hastada kardiyotoksisite nedeniyle kesildi. Azalan SoVEF her 2 hastada da başlangıç değerlerine geri dönmedi.
Sonuç: Mevcut çalışmada kardiyotoksisite insidansı (%1,69) tek başına trastuzumab için beklenenden daha yüksek değildi. Önceki çalışmalardan elde edilen veriler ve bu çalışmanın sonuçları pertuzumabın kardiyotoksisitede artışa neden olmadığını desteklemektedir. Yine de, gerçek yaşam koşullarında pertuzumabın kardiyak güvenliliğini desteklemek için büyük çaplı klinik çalışmalara ihtiyaç vardır.

Keywords

meme kanseri;, kardiyotoksisite;, pertuzumab

References

• Referans 1 Ross JS, Slodkowska EA, Symmans WF, Pusztai L, Ravdin PM, Hortobagyi GN. The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist 2009;14(4):320-368.
• Referans 2 Ahmed S, Sami A, Xiang J. HER2-directed therapy: current treatment options for HER2-positive breast cancer. Breast Cancer 2015;22(2):101-116.
• Referans 3 Yan M, Parker BA, Schwab R, Kurzrock R. HER2 aberrations in cancer: implications for therapy. Cancer Treat Rev 2014;40(6):770-780.
• Referans 4 Mendes D, Alves C, Afonso N, Cardoso F, Passos-Coelho JL, Costa L, et al. The benefit of HER2-targeted therapies on overall survival of patients with metastatic HER2-positive breast cancer--a systematic review. Breast Cancer Res 2015;17:140.
• Referans 5 Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 2013;24(9):2278-2284.
• Referans 6 Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 2012;13(1):25-32.
• Referans 7 Capelan M, Pugliano L, De Azambuja E, Bozovic I, Saini KS, Sotiriou C, et al. Pertuzumab: new hope for patients with HER2-positive breast cancer. Ann Oncol. 2013;24(2):273-282.
• Referans 8 Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012;366(2):109-119.
• Referans 9 Blumenthal GM, Scher NS, Cortazar P, Chattopadhyay S, Tang S, Song P, et al. First FDA approval of dual anti-HER2 regimen: pertuzumab in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer. Clin Cancer Res. 2013;19(18):4911-4916.
• Referans 10 Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001;344(11):783-792.
• Referans 11 Swain SM, Kim SB, Cortés J, Ro J, Semiglazov V, Campone M, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 2013;14(6):461-471.
• Referans 12 Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, et al. 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389(10075):1195-1205. Referans 13 von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, et al. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med 2017;377(2):122-131.
• Referans 14 Shao Z, Pang D, Yang H, Li W, Wang S, Cui S, et al. Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia: The PEONY Phase 3 Randomized Clinical Trial JAMA Oncol. 2020;6(3):e193692.
• Referans 15 Gradishar WJ, Anderson BO, Abraham J, Aft R, Agnese D, Allison KH, et al. Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2020;18(4):452-478.
• Referans 16 Vermeulen Z, Segers VF, De Keulenaer GW. ErbB2 signaling at the crossing between heart failure and cancer. Basic Res Cardiol 2016;111(6):60.
• Referans 17 Yu AF, Manrique C, Pun S, Liu JE, Mara E, Fleisher M, et al. Cardiac Safety of Paclitaxel Plus Trastuzumab and Pertuzumab in Patients With HER2-Positive Metastatic Breast Cancer. Oncologist 2016;21(4):418-424.
• Referans 18 Swain SM, Ewer MS, Cortés J, Amadori D, Miles D, Knott A, et al. Cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel in patients with HER2-positive metastatic breast cancer in CLEOPATRA: a randomized, double-blind, placebo-controlled phase III study. Oncologist 2013;18(3):257-264. Referans 19 Sendur MA, Aksoy S, Altundag K. Cardiotoxicity of novel HER2-targeted therapies. Curr Med Res Opin 2013;29(8):1015-1024.
• Referans 20 Lenihan D, Suter T, Brammer M, Neate C, Ross G, Baselga J. Pooled analysis of cardiac safety in patients with cancer treated with pertuzumab. Ann Oncol. 2012;23(3):791-800.
• Referans 21 Alhussein MM, Mokbel A, Cosman T, Aghel N, Yang EH, Mukherjee SD, et al. Pertuzumab Cardiotoxicity in Patients With HER2-Positive Cancer: A Systematic Review and Meta-analysis. CJC Open 2021;3(11):1372-1382.
• Referans 22 Valachis A, Nearchou A, Polyzos NP, Lind P. Cardiac toxicity in breast cancer patients treated with dual HER2 blockade. Int J Cancer 2013;133(9):2245-2252.