Erdem ÇUBUKÇU, Birol OCAK, Ömer Fatih ÖLMEZ, Adem DELİGÖNÜL, Turgut KAÇAN

Metastatik Meme Kanseri Tedavisinde Lapatinib Kapesitabin Kombinasyonun Etkinliğinin Retrospektif Değerlendirilmesi

Tüm dünyada meme kanseri kadınlarda kanserin ve kanser ilişkili ölümlerin en sık nedenidir. Meme kanserli hastaların %17–30 HER2 overekspresyonu olup hastalık kötü prognoz, hastalık progresyon riskinde artış, genel sağkalım ve progresyona kadar geçen sürenin her ikisinde azalma ile birliktedir. Lapatinib, HER2 ve epidermal büyüme faktör reseptör(EGFR) ün ilk dual tirozin kinaz inhibitörüdür. Bu çalışma da antrasiklin, taksan ve trastuzumab tedavisi sonrasında progrese olan metastatik meme kanserli hastalarda kapesitabin ve lapatinib kombinasyonunun etkisini ve tolerabilitesini inceledik. Medyan yaş 56 (34-76) olan toplam 24 hasta dosyası Eylül 2010-Mayıs 2018 arasında 3 merkezde retrospektif olarak incelendi. Tüm hastalar taksan ve antrasiklin içeren kemoterapi ve trastuzumab sonrası progrese olan HER2 pozitif metastatik meme kanseri hastalardı. Genel cevap oranı %29.1, 2 komplet yanıt (CR, 8.3%), 5 parsiyel yanıt (PR, 20.8%), ve 7 stabil hastalık (SD, 29.1%) olmak üzere sağlandı. Kapesitabin ve lapatinib kombinasyon tedavisi antrasiklin, taksan ve trastuzumab tedavisi sonrasında progrese olan metastatik meme kanserli hastalarda etkili ve iyi tolere edilmiştir.

Anahtar Kelimeler:

lapatinib, meme kanseri, metastatik

Retrospective Evaluation of the Efficacy of Lapatinib Capecitabine in the Treatment of Metastatic Breast Cancer

Worldwide, breast cancer is the most common malignancy and cause of cancer-related death in women. In the 17%–30% of breast cancer patients who overexpress ErbB2 (HER2), the disease is associated with poorer prognosis, greater risk for disease progression and reductions in both progression free survival (PFS) and overall survival (OS). Lapatinib is the first dual tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 (HER2/neu) and epidermal growth factor receptor (EGFR). The present study evaluated the efficacy and tolerability of the combination of lapatinib and capecitabine in patients with metastatic breast cancer (MBC) who progressed after therapy with trastuzumab, a taxane and/or anthracycline. A total of 24 patients with a median age of 56 (34-76) were evaluated retrospectively in 3 centers between September 2010 and May 2018. All the patients had HER2 positive MBC progressing after trastuzumab and chemotherapy including an anthracycline and/or taxane. An overall response rate (ORR) of 29.1% was achieved including 2 complete responses (CR, 8.3%), 5 partial responses (PR, 20.8%), and 7 stable disease (SD, 29.1%). Lapatinib and capecitabine combination therapy is effective and well tolerated in patients with MBC who had progressive disease after trastuzumab, taxane, and/or anthracycline therapy.

Keywords:

lapatinib, breast cancer, metastatic,

PDF

___

Kaynaklar
1. Siegel RL, Miller KD, Jemal A. Cancer statistics,2016. CA Cancer J Clin2016;66:7-30.2. 2. Zahnow CA. ErbB receptors and their ligands in the breast. Expert Rev Mol Med 2006; 8: 1–21.
3. Zhang H, Berezov A, Wang Q et al. ErbB receptors: from oncogenes to targeted cancer therapies. J Clin Invest 2007; 117: 2051–58
4. Badache A, Goncalves A. The ErbB2 signaling network as a target for breast cancer therapy. J Mammary Gland Biol Neoplasia 2006; 11: 13–25.
5. Slamon DJ, Godolphin W, Jones LA et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989; 244: 707–12.
6. Swain SM, Baselga J, Kim SB, et al. CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015; 19;372(8):724-34.
7. Gamucci T, Pizzuti L, Natoli C, Mentuccia L, Sperduti I, Barba M, A multicenter REtrospective observational study of first-line treatment with PERtuzumab, trastuzumab and taxanes for advanced HER2 positive breast cancer patients. RePer Study. Cancer Biol Ther. 2018; 7:1-9.
8. Medina PJ, Goodin S. Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clin Ther. 2008;30(8):1426-47.
9. Johnston S, Pegram M, Press M et al. Lapatinib combined with letrozole vs. letrozole alone for front line postmenopausal hormone receptor positive (HR+) metastatic breast cancer (MBC): first results from the EGF30008 Trial. Abstract presented at 31st Annual San Antonio Breast Cancer Symposium; December 10–14, 2008;
10. Ro J, Park S, Kim S, et al. Clinical outcomes of HER2-positive metastatic breast cancer patients with brain metastasis treated with lapatinib and capecitabine: an open-label expanded Access study in Korea. BMC Cancer. 2012;28;12:322-3.
18. Capri G, Chang J, Chen SC, et al. An open-label expanded access study of lapatinib and capecitabine in patients with HER2-overexpressing locally advanced or metastatic breast cancer. Ann Oncol 2010;21(3):474-80.
12. Gomez HL, Doval DC, Chavez MA, et al. Efficacy and safety of lapatinib as firstline therapy for HER2-amplified locally advanced or metastatic breast cancer. J Clin Oncol 2008;26:2999–3005
13. Giordano SH, Temin S, Kirshner JJ, et al. Systemic therapy for patients with advanced human epidermal growth factor receptor 2–positive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2014;32:2078–99.
14. Leung HWC, Leung JH, Chan ALF. Efficacy and safety of a combination of HER2-targeted agents as first-line treatment for metastatic HER2-positive breast cancer: a network meta-analysis. Expert Opin Drug Saf. 2018;17(1):1-7.
15. Tian T, Ye J, Zhou S. Effect of pertuzumab, trastuzumab, and docetaxel inHER2-positive metastatic breast cancer: A meta-analysis . Int J Clin Pharmacol Ther. 2017;55(9):720-727.
16. Perez EA, Barrios C, Eiermann Wet al. Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2-Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study. J Clin Oncol. 2017 Jan 10;35(2):141-48.
17. Fabi A, De Laurentiis M, Caruso M, et al.. Efficacy and safety of T-DM1 in the 'common-practice' of HER2+ advanced breast cancer setting: a multicenter study. Oncotarget 2017 18;8(38):64481-89.
19. Cameron D, Casey M, Press M, et al. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat 2008;112:533–43.
20. Clayton AJ, Danson S, Jolly S, et al. Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer. Br J Cancer 2004;91:639–43.
21. Lin NU, Bellon JR, Winer EP. CNS metastases in breast cancer. J Clin Oncol 2004;22:608–17.
22. Cetin B, Benekli M, Oksuzoglu B, et al. Lapatinib plus capecitabine for brain metastases in patients with human epidermal growth factor receptor 2-positive advanced breast cancer. Onkologie 2012;35:740–45.
23. Geyer CE, Orster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2- positive advanced breast cancer N Engl J Med. 2006;355:2733– 43.