Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

The Lancet Oncology

Volumn 17, Issue 3, 2016, Pages 367-377

  Chan, Arlene ^a   Delaloge, Suzette ^b   Holmes, Frankie A ^c   Moy, Beverly ^d   Iwata, Hiroji ^e   Harvey, Vernon J ^f   Robert, Nicholas J ^g   Silovski, Tajana ^h   Gokmen, Erhan ⁱ   von Minckwitz, Gunter ^j   Ejlertsen, Bent ^k   Chia, Stephen K L ^l   Mansi, Janine ^m   Barrios, Carlos H ⁿ   Gnant, Michael ^o   Buyse, Marc ^p   Gore, Ira ^q   Smith, John ^r   Harker, Graydon ^s   Masuda, Norikazu ^t   Petrakova, Katarina ^u   Zotano, Angel Guerrero ^v   Iannotti, Nicholas ^w   Rodriguez, Gladys ^c   Tassone, Pierfrancesco ^x   Wong, Alvin ^y   Bryce, Richard ^y   Ye, Yining ^y   Yao, Bin ^y   Martin, Miguel ^z   more..

^a CURTIN UNIVERSITY   (Australia)

^b INSTITUT GUSTAVE ROUSSY   (France)

^c TEXAS ONCOLOGY   (United States)

^d MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

^e AICHI CANCER CENTER HOSPITAL   (Japan)

^f AUCKLAND CITY HOSPITAL   (New Zealand)

^g Fairfax Northern Virginia Hematology Oncology   (United States)

^h SESTRE MILOSRDNICE UNIVERSITY HOSPITAL   (Croatia)

ⁱ EGE UNIVERSITY SCHOOL OF MEDICINE   (Turkey)

^j German Breast Group Forschungs GmbH   (Germany)

^k Rigshospitalet   (Denmark)

^l BRITISH COLUMBIA CANCER AGENCY   (Canada)

^m GUY'S AND ST THOMAS' NHS FOUNDATION TRUST   (United Kingdom)

ⁿ PONTIFICAL CATHOLIC UNIVERSITY OF RIO GRANDE DO SUL   (Brazil)

^o MEDICAL UNIVERSITY OF VIENNA   (Austria)

^p INTERNATIONAL DRUG DEVELOPMENT INSTITUTE   (Belgium)

^q University Alabama   (United States)

^r Northwest Cancer Specialists   (United States)

^s Utah Cancer Specialists   (United States)

^t OSAKA NATIONAL HOSPITAL   (Japan)

^u MASARYK MEMORIAL CANCER INSTITUTE   (Czech Republic)

^v INSTITUTO VALENCIANO DE ONCOLOGÍA   (Spain)

^w Hematology Oncology Associates of Treasure Coast   (United States)

^x UNIVERSITY MAGNA GRAECIA OF CATANZARO   (Italy)

^y Puma Biotechnology Inc   (United States)

^z UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

more..

Author keywords

[No Author keywords available]

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR 2; NERATINIB; PLACEBO; TRASTUZUMAB; ANTINEOPLASTIC AGENT; N-(4-(3-CHLORO-4-(2-PYRIDINYLMETHOXY)ANILINO)-3-CYANO-7-ETHOXY-6-QUINOLYL)-4-(DIMETHYLAMINO)-2-BUTENAMIDE; QUINOLINE DERIVATIVE;

ABDOMINAL PAIN; ACUTE MYELOBLASTIC LEUKEMIA; ADULT; ARTHRALGIA; ARTICLE; ASIA; AUSTRALIA; BRAIN HEMORRHAGE; BRAIN TUMOR; BREAST CANCER; CANCER ADJUVANT THERAPY; CANCER STAGING; CONTROLLED STUDY; DECREASED APPETITE; DIARRHEA; DISEASE FREE SURVIVAL; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; ESTROGEN RECEPTOR POSITIVE BREAST CANCER; EUROPE; FATIGUE; FEMALE; FOLLOW UP; HEADACHE; HEART INFARCTION; HEART LEFT VENTRICLE EJECTION FRACTION; HUMAN; INTENTION TO TREAT ANALYSIS; INTERACTIVE VOICE RESPONSE SYSTEM; INTERSTITIAL LUNG DISEASE; JAPAN; LUNG FIBROSIS; LYMPH NODE METASTASIS; MAJOR CLINICAL STUDY; MULTICENTER STUDY; MUSCLE SPASM; NAUSEA; NEW ZEALAND; NORTH AMERICA; OUTCOME ASSESSMENT; PATIENT COMPLIANCE; PHASE 3 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PROGESTERONE RECEPTOR POSITIVE BREAST CANCER; PROTEIN EXPRESSION; QT PROLONGATION; RANDOMIZED CONTROLLED TRIAL; RASH; RISK BENEFIT ANALYSIS; SOUTH AMERICA; STOMACH CANCER; TREATMENT DURATION; UPPER ABDOMINAL PAIN; VOMITING; ADJUVANT CHEMOTHERAPY; AGED; BREAST NEOPLASMS; CLINICAL TRIAL; DOSE RESPONSE; DRUG ADMINISTRATION; INTERNATIONAL COOPERATION; KAPLAN MEIER METHOD; MASTECTOMY; METABOLISM; MIDDLE AGED; MORTALITY; PATHOLOGY; PROCEDURES; PROPORTIONAL HAZARDS MODEL; SURVIVAL ANALYSIS; TREATMENT OUTCOME; TUMOR INVASION;

ADULT; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BREAST NEOPLASMS; CHEMOTHERAPY, ADJUVANT; DISEASE-FREE SURVIVAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; FEMALE; FOLLOW-UP STUDIES; HUMANS; INTERNATIONALITY; KAPLAN-MEIER ESTIMATE; MASTECTOMY; MIDDLE AGED; NEOPLASM INVASIVENESS; NEOPLASM STAGING; PROPORTIONAL HAZARDS MODELS; QUINOLINES; RECEPTOR, ERBB-2; SURVIVAL ANALYSIS; TRASTUZUMAB; TREATMENT OUTCOME;

EID: 84960488751     PISSN: 14702045     EISSN: 14745488     Source Type: Journal    
DOI: 10.1016/S1470-2045(15)00551-3     Document Type: Article

References (38)

1. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987, 235:177-182.
2. Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol 2014, 32:3744-3752.
3. Gianni L, Dafni U, Gelber RD, et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol 2011, 12:236-244.
4. Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 2011, 365:1273-1283.
5. Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, et al. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet 2013, 382:1021-1028.
6. Joensuu H, Bono P, Kataja V, et al. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer Trial. J Clin Oncol 2009, 27:5685-5692.
7. Wong KK, Fracasso PM, Bukowski RM, et al. A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors. Clin Cancer Res 2009, 15:2552-2558.
8. Burstein HJ, Sun Y, Dirix LY, et al. Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer. J Clin Oncol 2010, 28:1301-1307.
9. Nahta R, Esteva FJ HER2 therapy: molecular mechanisms of trastuzumab resistance. Breast Cancer Res 2006, 8:215.
10. Martin M, Bonneterre J, Geyer CE, et al. A phase two randomised trial of neratinib monotherapy versus lapatinib plus capecitabine combination therapy in patients with HER2+ advanced breast cancer. Eur J Cancer 2013, 49:3763-3772.
11. Perez EA, Suman VJ, Davidson NE, et al. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol 2011, 29:4491-4497.
12. Slamon D, Eiermann W, Robert N, et al. BCIRG 006 Phase III trial comparing AC→T with AC→TH and with TCH in the adjuvant treatment of HER2-amplified early breast cancer patients: third planned efficacy analysis (accessed Jan 26, 2016). http://bit.ly/1JTxDOr.
13. Weinstein IB, Joe AK Mechanisms of disease: oncogene addiction-a rationale for molecular targeting in cancer therapy. Nat Clin Pract Oncol 2006, 3:448-457.
14. Wang YC, Morrison G, Gillihan R, et al. Different mechanisms for resistance to trastuzumab versus lapatinib in HER2-positive breast cancers-role of estrogen receptor and HER2 reactivation. Breast Cancer Res 2011, 13:R121.
15. von Minckwitz G, du Bois A, Schmidt M, et al. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a German Breast Group 26/Breast International Group 03-05 study. J Clin Oncol 2009, 27:1999-2006.
16. Blackwell KL, Burstein HJ, Storniolo AM, et al. Randomized study of lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol 2010, 28:1124-1130.
17. Weinstein IB, Joe A Oncogene addiction. Cancer Res 2008, 68:3077-3080.
18. Fleiss JL Analysis of data from multiclinic trials. Control Clin Trials 1986, 7:267-275.
19. Untch M, Gelber RD, Jackisch C, et al. Estimating the magnitude of trastuzumab effects within patient subgroups in the HERA trial. Ann Oncol 2008, 19:1090-1096.
20. Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2 negative cohort. Lancet 2010, 375:377-384.
21. Gianni L, Pienkowski T, Im YH, 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, 13:25-32.
22. de Azambuja E, Holmes AP, Piccart-Gebhart M, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol 2014, 15:1137-1146.
23. De Laurentiis M, Arpino G, Massarelli E, et al. A meta-analysis on the interaction between HER-2 expression and response to endocrine treatment in advanced breast cancer. Clin Cancer Res 2005, 11:4741-4748.
24. Dowsett M, Harper-Wynne C, Boeddinghaus I, et al. HER-2 amplification impedes the antiproliferative effects of hormone therapy in estrogen receptor-positive primary breast cancer. Cancer Res 2001, 61:8452-8458.
25. Nahta R, O'Regan RM Therapeutic implications of estrogen receptor signaling in HER2-positive breast cancers. Breast Cancer Res Treat 2012, 135:39-48.
26. Kurokawa H, Lenferink AE, Simpson JF, et al. Inhibition of HER2/neu (erbB-2) and mitogen-activated protein kinases enhances tamoxifen action against HER2-overexpressing, tamoxifen-resistant breast cancer cells. Cancer Res 2000, 60:5887-5894.
27. Canonici A, Gijsen M, Mullooly M, et al. Neratinib overcomes trastuzumab resistance in HER2 amplified breast cancer. Oncotarget 2013, 4:1592-1605.
28. Pestalozzi BC, Holmes E, de Azambuja E, et al. CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab: a retrospective substudy of the HERA trial (BIG 1-01). Lancet Oncol 2013, 14:244-248.
29. Awada A, Colomer R, Inoue K, et al. Neratinib plus paclitaxel vs trastuzumab plus paclitaxel in previously untreated metastatic HER2-positive breast cancer: the NEfERT-T randomized clinical trial. JAMA Oncol (in press).
30. Andreyev J, Ross P, Donnellan C, et al. Guidance on the management of diarrhoea during cancer chemotherapy. Lancet Oncol 2014, 15:e447-e460.
31. Besse B, Soria J, Yao B, et al. Neratinib with or without temsirolimus in patients with non-small cell lung cancer (NSCLC) carrying HER2 somatic mutations: an international randomized phase II study. Ann Oncol 2014, 25:1-41. (A39 abstr).
32. Gajria D, Modi S, Saura C, et al. A phase I/II study of neratinib plus temsirolimus in HER2+ metastatic breast cancer reveals ongoing HER2 pathway dependence in many patients despite several lines of HER2 targeted therapy. Cancer Res 2015, 75(suppl 9). P5-19-04.
33. Jankowitz RC, Abraham J, Tan AR, et al. Safety and efficacy of neratinib in combination with weekly paclitaxel and trastuzumab in women with metastatic HER2-positive breast cancer: an NSABP Foundation Research Program phase I study. Cancer Chemother Pharmacol 2013, 72:1205-1212.
34. Eton DT, Cella D, Yost KJ, et al. A combination of distribution- and anchor-based approaches determined minimally important differences (MIDs) for four endpoints in a breast cancer scale. J Clin Epidemiol 2004, 57:898-910.
35. Pickard AS, Neary MP, Cella D Estimation of minimally important differences in EQ-5D utility and VAS scores in cancer. Health Qual Life Outcomes 2007, 5:70.
36. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005, 353:1659-1672.
37. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005, 353:1673-1684.
38. Mann BS, Johnson JR, Kelly R, Sridhara R, Williams G, Pazdur R Letrozole in the extended adjuvant treatment of postmenopausal women with history of early-stage breast cancer who have completed 5 years of adjuvant tamoxifen. Clin Cancer Res 2005, 11:5671-5677.