Метастазы HER2-позитивного рака молочной железы в головном мозге: новые возможности системной терапии

Артамонова Е.В., Манзюк Л.В. Метастазы HER2-позитивного рака молочной железы в головном мозге: новые возможности системной терапии. Современная онкология. 2015; 17 (2): 35–39.

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Artamonova E.V., Manziuk L.V. Brain metastases in HER2-positive breast cancer: new opportunities for systemic therapy. Journal of modern oncology. 2015; 17 (2): 35–39.

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Аннотация

В статье обсуждаются новые возможности лечения HER2-позитивного рака молочной железы с поражением центральной нервной системы (ЦНС). В исследовании CEREBEL было показано, что трастузумаб не уступает лапатинибу в отношении снижения частоты развития метастазов в головном мозге и имеет достоверные преимущества по выживаемости без прогрессирования болезни. Новая стратегия 1-й линии терапии диссеминированного HER2-позитивного рака молочной железы заключается в применении двойной блокады рецептора с помощью двух моноклональных антител (трастузумаб + пертузумаб) в комбинации с таксаном. Этот подход оказался высокоэффективным, в том числе в отношении поражения ЦНС: добавление пертузумаба к комбинации трастузумаб + доцетаксел увеличивало медиану времени до выявления метастазов в головном мозге как первой локализации прогрессирования с 11,9 до 15 мес и медиану общей выживаемости больных этой подгруппы с 26,3 до 34,4 мес. При прогрессировании HER2-позитивного метастатического рака молочной железы после трастузумаба и таксанов было доказано преимущество нового препарата T-DM1 перед комбинацией лапатиниба с капецитабином, в том числе у больных с метастазами в головном мозге: абсолютный выигрыш в медиане общей выживаемости в этой подгруппе достиг 13,9 мес.

Ключевые слова: HER2-позитивный рак молочной железы, метастазы в головном мозге, трастузумаб, лапатиниб, пертузумаб, T-DM1.

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This article dials with the new opportunities for the treatment of HER2-positive breast cancer with the involvement of the central nervous system (CNS). In CEREBEL study was shown that trastuzumab was not inferior to lapatinib concerning the reduction the incidence of brain metastases and had statistically significant progression-free survival advantages. The new strategy of the 1st-line therapy in disseminated HER2-positive breast cancer is to apply dual receptor blockade using two monoclonal antibodies (trastuzumab + pertuzumab) in combination with taxanes. This approach has been highly effective, even in the patients with the involvement of the CNS: the addition of pertuzumab into the combination of trastuzumab + docetaxel has increased the median time to development of CNS metastases as first site of disease progression from 11,9 to 15 months, and median overall survival – from 26,3 to 34,4 months. On the progression of HER2-positive metastatic breast cancer after usage of trastuzumab and taxanes, the advantage of new drug – T-DM1 was proven over the combination of lapatinib and capecitabin, even in the patients with brain metastases: the advantage of median overall survival in these patients was reached 13,9 months.

Key words: HER2-positive breast cancer, brain metastases, trastuzumab, lapatinib, pertuzumab, T-DM1.

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Список литературы

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23. Swain S, Baselga J, Kim S et al. Pertuzumab, trastuzumab, and docetaxel in HER2¬positive metastatic breast cancer. N Engl J Med 2015; 372: 724–34.
24. Swain S, Baselga J, Miles D et al. Incidence of central nervous system metastases in patients with HER2-positive metastatic breast cancer treated with pertuzumab, trastuzumab, and docetaxel: results from the randomized phase III study CLEOPATRA. Ann Oncol 2014; 25: 1116–21.
25. Swain SM, Kim S-B, Cortés J et al. Final overall survival (OS) analysis from CLEOPATRA study of first-line (1L) pertuzumab (Ptz), trastuzumab (T), and docetaxel (D) in patients with HER2-positive metastatic breast cancer (MBC). ESMO 2014: Abstr. 350 Oral Presentation 28.09.2014, Madrid.
26. Lewis Phillips GD, Li G, Dugger D et al. Targeting HER2-Positive Breast Cancer with Trastuzumab-DM1, an Antibody–Cytotoxic Drug Conjugate. Cancer Res 2008; 68: 22, p. 9280–90.
27. Verma S, Miles D, Gianni L et al. Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer. N Eng J Med 2012; 367: 1783–91.
28. Krop I, Lin N, Blackwell K et al. Efficacy and Safety of Trastuzumab Emtansine (T-DM1) vs Lapatinib Plus Capecitabine in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer and Central Nervous System Metastases: Results From a Retrospective Exploratory Analysis of EMILIA. SABCS 2013: P4-12-27 (and associated poster presentation).
29. Krop I, Lin N, Blackwell K et al. Trastuzumab Emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA Annals of Oncology 2015; 26 (1): 113–19.
30. Krop IE, Kim SB, Gonzalez-Martin A et al. Trastuzumab Emtansine (T-DM1) versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol 2014; 15 (7): 689–99.
31. Bachelot T, Romieu G, Campone M et al. Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): A single- group phase 2 study. Lancet Oncol 2013; 14: 64–71.

________________________________________________

1. http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx
2. Kaprin A.D., Starinskii V.V., Petrova G.V. Zlokachestvennye novoobrazovaniia v Rossii v 2013 g. (Zabolevaemost' i smertnost'). M., 2015. [in Russian]
3. Kaprin A.D., Starinskii V.V., Petrova G.V. Sostoianie onkologicheskoi pomoshchi naseleniiu Rossii v 2013 godu. M., 2014. [in Russian]
4. Tsukada Y, Fouad A, Pickren JW, Lane WW. Central nervous system metastasis from breast carcinoma. Autopsy study. Cancer 1983; 52: 2349–54.
5. Cho SY, Choi HY. Causes of death and metastatic patterns in patients with mammary cancer. Ten-year autopsy study. Am J Clin Pathol 1980; 73: 232–4.
6. Chang E, Lob S. Diagnosis and Management of Central Nervous System Metastases from Breast Cancer. The Oncologist 2003; 8 (5): 398–410.
7. Lin NU, Bellon JR, Winer EP. CNS metastases in breast cancer. J Clin Oncol 2004; 22: 3608–17.
8. 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.
9. Burstein HJ, Lieberman G, Slamon DJ et al. Isolated central nervous system metastases in patients with HER2-overexpressing advanced breast cancer treated with first- line trastuzumab-based therapy. Ann Oncol 2005; 16: 1772–7.
10. Wardley AM, Danson S, Clayton AJ et al. High incidence of brain metastases in patients treated with trastuzumab for metastatic breast cancer at a large cancer center. Proc Am Soc Clin Oncol 2002; 21: 61a, abstr 241.
11. Pestalozzi BC, Zahrieh D, Price KN et al. Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG) Ann Oncol 2006; 17: 935–44.
12. Khuntia D, Brown P, Li J et al. Whole- brain radiotherapy in the management of brain metastasis. J Clin Oncol 2006; 24: 1295–304.
13. Hikino H, Yamada T, Johbara K et al. Potential role of chemo-radiation with oral capecitabine in a breast cancer patient with central nervous system relapse. Breast 2006; 15: 97–9.
14. Gelmon KA, Boyle F, Kaufman B et al. Open-label phase III randomized kontrolled trial comparing taxane-based chemotherapy (Tax) with lapatinib (L) or trastuzumab (T) as first-line therapy for women with HER2+ metastatic breast cancer: Interim analysis (IA) of NCIC CTG MA.31/GSK EGF 108919. ASCO 2012, Journal of Clinical Oncology, 2012; ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2012; 30 (18) (Suppl.),: LBA671.
15. Gelmon KA, Boyle F, Kaufman B et al. Lapatinib or trastuzumab plus taxane therapy for Human Epidermal Growth Factor Receptor-2-positive advanced breast cancer% final results of NCIC CTG MA.31. JCO 2015; 33 (14): 1574–83.
16. Geyer CE, Martin A, Newstat B et al. Lapatinib (L) plus capecitabine (C) in HER2+ advanced breast cancer (ABC): Genomic and updated efficacy data. 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition). J Clin Oncol 2007; 25 (18S): Abstract 1035.
17. Pivot X, Semiglazov V, Zurawski B et al. CEREBEL (EGF111438): An open label randomized phase III study comparing the incidence of CNS metastases in patients (pts) with HER2+ metastatic breast cancer (MBC), treated with lapatinib plus capecitabine (LC) versus trastuzumab plus capecitabine (TC). Oral presentation and abstract presented at: European Society for Medical Oncology; October 1, 2012; Vienna, Austria. ESMO Oral Presentation, 2012. Available at: http://abstracts.webges.com/myitinerary/ session-128.html?congress=esmo2012. Accessed January 14, 2013.
18. Pivot X, Manikhas A, Zurawski B et al. CEREBEL (EGF111438): A Phase III, Randomized, Open Label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with Human Epidermal Growth Factor Receptor-2 metastatic breast cancer. JCO 2016; 33 (14): 1564–73.
19. Bartsch R, Berghoff A, Pluschnig U et al. Impact of anti-HER2 therapy on overall survival in HER2-overexpressing breast cancer patients with brain metastases. Br J Cancer 2012; 106: 25–31.
20. Baselga J, Cortes J, Kim SB et al. Pertuzumab + trastuzumab + docetaxel for metastatic breast cancer. N Engl J Med 2012; 336: 109–19.
21. Swain SM, Kim S-B, Cortés J et al. Confirmatory overall survival (OS) analysis of CLEOPATRA: a randomized, double-blind, placebo-controlled Phase III study with pertuzumab (P), trastuzumab (T), and docetaxel (D) in patients (pts) with HER2-positive first-line (1L) metastatic breast cancer (MBC). Cancer Res 2012; 72 (15) (Suppl.): Abstract P5–18–26.
22. Swain SM, Kim SB, Cortes J et al. Pertuzumab, trastuzumab, and docetaxel for HER2 – positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomized, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 2013; 14: 461–71.
23. Swain S, Baselga J, Kim S et al. Pertuzumab, trastuzumab, and docetaxel in HER2¬positive metastatic breast cancer. N Engl J Med 2015; 372: 724–34.
24. Swain S, Baselga J, Miles D et al. Incidence of central nervous system metastases in patients with HER2-positive metastatic breast cancer treated with pertuzumab, trastuzumab, and docetaxel: results from the randomized phase III study CLEOPATRA. Ann Oncol 2014; 25: 1116–21.
25. Swain SM, Kim S-B, Cortés J et al. Final overall survival (OS) analysis from CLEOPATRA study of first-line (1L) pertuzumab (Ptz), trastuzumab (T), and docetaxel (D) in patients with HER2-positive metastatic breast cancer (MBC). ESMO 2014: Abstr. 350 Oral Presentation 28.09.2014, Madrid.
26. Lewis Phillips GD, Li G, Dugger D et al. Targeting HER2-Positive Breast Cancer with Trastuzumab-DM1, an Antibody–Cytotoxic Drug Conjugate. Cancer Res 2008; 68: 22, p. 9280–90.
27. Verma S, Miles D, Gianni L et al. Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer. N Eng J Med 2012; 367: 1783–91.
28. Krop I, Lin N, Blackwell K et al. Efficacy and Safety of Trastuzumab Emtansine (T-DM1) vs Lapatinib Plus Capecitabine in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer and Central Nervous System Metastases: Results From a Retrospective Exploratory Analysis of EMILIA. SABCS 2013: P4-12-27 (and associated poster presentation).
29. Krop I, Lin N, Blackwell K et al. Trastuzumab Emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA Annals of Oncology 2015; 26 (1): 113–19.
30. Krop IE, Kim SB, Gonzalez-Martin A et al. Trastuzumab Emtansine (T-DM1) versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol 2014; 15 (7): 689–99.
31. Bachelot T, Romieu G, Campone M et al. Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): A single- group phase 2 study. Lancet Oncol 2013; 14: 64–71.

Авторы

Е.В.Артамонова*, Л.В.Манзюк

ФГБНУ Российский онкологический научный центр им. Н.Н.Блохина. 115478, Россия, Москва, Каширское ш., д. 23
*artamonovae@mail.ru

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E.V.Artamonova*, L.V.Manziuk

N.N.Blochin Russian Cancer Research Center. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23
*artamonovae@mail.ru

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