Relationship between tumor biomarkers and efficacy in TH3RESA, a phase III study of trastuzumab emtansine (T-DM1) vs. treatment of physician's choice in previously treated HER2-positive advanced breast cancer

International Journal of Cancer

Volumn 139, Issue 10, 2016, Pages 2336-2342

  Kim, Sung Bae ^a   Wildiers, Hans ^b   Krop, Ian E ^c   Smitt, Melanie ^d   Yu, Ron ^d   Lysbet de Haas, Sanne ^e   Gonzalez Martin, Antonio ^f  

^a University of Ulsan College of Medicine   (South Korea)

^b UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^c DANA FARBER CANCER INSTITUTE   (United States)

^d GENENTECH INC   (United States)

^e F HOFFMANN LA ROCHE LTD   (Switzerland)

^f MD ANDERSON CANCER CENTER   (Spain)

Author keywords

ado trastuzumab emtansine; biomarkers; HER2; metastatic breast cancer; T DM1

Indexed keywords

BIOLOGICAL MARKER; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 3; MESSENGER RNA; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PHOSPHOINOSITIDE 3 KINASE CATALYTIC SUBUNIT ALPHA; TRASTUZUMAB EMTANSINE; UNCLASSIFIED DRUG;

ARTICLE; BREAST CANCER; CONTROLLED STUDY; DRUG EFFICACY; GENE; GENE MUTATION; HUMAN; MAJOR CLINICAL STUDY; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); TREATMENT RESPONSE;

EID: 84986627812     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.30276     Document Type: Article

References (23)

1. Lewis Phillips GD, Li G, Dugger DL, et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody–cytotoxic drug conjugate. Cancer Res 2008;68:9280–90.
2. Junttila TT, Li G, Parsons K, et al. Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res Treat 2011;128:347–56.
3. Yakes FM, Chinratanalab W, Ritter CA, et al. Herceptin-induced inhibition of phosphatidylinositol-3 kinase and Akt is required for antibody-mediated effects on p27, cyclin D1, and antitumor action. Cancer Res 2002;62:4132–41.
4. Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012;367:1783–91.
5. Krop IE, Kim SB, González-Martín A, et al. Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol 2014;15:689–99.
6. Burris HA, 3rd, Rugo HS, Vukelja SJ, et al. Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy. J Clin Oncol 2011;29:398–405.
7. Krop IE, LoRusso P, Miller KD, et al. A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. J Clin Oncol 2012;30:3234–41.
8. Miller KD, Diéras V, Harbeck N, et al. Phase IIa trial of trastuzumab emtansine with pertuzumab for patients with human epidermal growth factor receptor 2-positive, locally advanced, or metastatic breast cancer. J Clin Oncol 2014;32:1437–44.
9. Perez EA, Hurvitz SA, Amler LC, et al. Relationship between HER2 expression and efficacy with first-line trastuzumab emtansine compared with trastuzumab plus docetaxel in TDM4450g: a randomized phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Breast Cancer Res 2014;16:R50
10. Baselga J, Verma S, Ro J, et al. Relationship between tumor biomarkers (BM) and efficacy in EMILIA, a phase 3 study of trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer (MBC). Cancer Res 2013; 73: Abstract nr LB-63.
11. Duronio V, Scheid MP, Ettinger S. Downstream signalling events regulated by phosphatidylinositol 3-kinase activity. Cell Signal 1998;10:233–9.
12. Vanhaesebroeck B, Waterfield MD. Signaling by distinct classes of phosphoinositide 3-kinases. Exp Cell Res 1999;253:239–54.
13. Isakoff SJ, Engelman JA, Irie HY, et al. Breast cancer-associated PIK3CA mutations are oncogenic in mammary epithelial cells. Cancer Res 2005;65:10992–11000.
14. Cantley LC, Neel BG. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci U S A 1999;96:4240–5.
15. Nagata Y, Lan KH, Zhou X, et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 2004;6:117–27.
16. Berns K, Horlings HM, Hennessy BT, et al. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 2007;12:395–402.
17. Eichhorn PJ, Gili M, Scaltriti M, et al. Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235. Cancer Res 2008;68:9221–30.
18. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228–47.
19. Esteva FJ, Guo H, Zhang S, et al. PTEN, PIK3CA, p-AKT, and p-p70S6K status: association with trastuzumab response and survival in patients with HER2-positive metastatic breast cancer. Am J Pathol 2010;177:1647–56.
20. Razis E, Bobos M, Kotoula V, et al. Evaluation of the association of PIK3CA mutations and PTEN loss with efficacy of trastuzumab therapy in metastatic breast cancer. Breast Cancer Res Treat 2011;128:447–56.
21. Park YH, Jung HA, Choi MK, et al. Role of HER3 expression and PTEN loss in patients with HER2-overexpressing metastatic breast cancer (MBC) who received taxane plus trastuzumab treatment. Br J Cancer 2014;110:384–91.
22. Baselga J, Cortés J, Im SA, et al. Biomarker analyses in CLEOPATRA: a phase III, placebo-controlled study of pertuzumab in human epidermal growth factor receptor 2-positive, first-line metastatic breast cancer. J Clin Oncol 2014;32:3753–61.
23. Schneeweiss A, Chia S, Hegg R, et al. Evaluating the predictive value of biomarkers for efficacy outcomes in response to pertuzumab- and trastuzumab-based therapy: an exploratory analysis of the TRYPHAENA study. Breast Cancer Res 2014;16:R73