A phase II trial to assess efficacy and safety of afatinib in extensively pretreated patients with HER2-negative metastatic breast cancer

Breast Cancer Research and Treatment

Volumn 134, Issue 3, 2012, Pages 1149-1159

  Schuler, Martin ^a   Awada, Ahmad ^b   Harter, Philipp ^c   Canon, Jean Luc ^d   Possinger, Kurt ^e   Schmidt, Marcus ^f   De Grève, Jacques ^g   Neven, Patrick ^h   Dirix, Luc ⁱ   Jonat, Walter ^j   Beckmann, Matthias W ^k   Schütte, Jochen ^l   Fasching, Peter A ^k   Gottschalk, Nina ^m   Besse Hammer, Tatiana ^b   Fleischer, Frank ⁿ   Wind, Sven ⁿ   Uttenreuther Fischer, Martina ⁿ   Piccart, Martine ^b   Harbeck, Nadia ^o  

^a UNIVERSITY HOSPITAL ESSEN   (Germany)

^b JULES BORDET INSTITUTE   (Belgium)

^c DR HORST SCHMIDT KLINIKEN   (Germany)

^d Grand Hopital de Charleroi   (Belgium)

^e CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^f UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

^g UNIVERSITY HOSPITAL BRUSSELS   (Belgium)

^h UNIVERSITY HOSPITALS LEUVEN   (Belgium)

ⁱ SINT AUGUSTINUS HOSPITAL   (Belgium)

^j UNIVERSITY OF KIEL   (Germany)

^k UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^l MARIEN HOSPITAL DÜSSELDORF   (Germany)

^m TECHNICAL UNIVERSITY OF MUNICH   (Germany)

ⁿ BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

^o LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

more..

Author keywords

Afatinib; EGFR TKI; HER2 negative breast cancer; Metastatic breast cancer; Triple negative breast cancer

Indexed keywords

AFATINIB; ESTROGEN RECEPTOR; PROGESTERONE RECEPTOR;

ADULT; AGED; AORTA STENOSIS; ARTICLE; BREAST CANCER; BREAST METASTASIS; CANCER GROWTH; CANCER SURVIVAL; CHRONIC OBSTRUCTIVE LUNG DISEASE; CONTINUOUS INFUSION; CONTROLLED STUDY; DIARRHEA; DOSE RESPONSE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; DRUG SCREENING; DRUG WITHDRAWAL; GASTROINTESTINAL DISEASE; HEART EJECTION FRACTION; HEART VENTRICLE FAILURE; HUMAN; HUMAN TISSUE; HYPERTENSION; KIDNEY FAILURE; LUNG EMBOLISM; MAJOR CLINICAL STUDY; METASTASIS; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; SIDE EFFECT; SKIN DISEASE; SURVIVAL RATE; SURVIVAL TIME; TREATMENT DURATION;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; COHORT STUDIES; FEMALE; HUMANS; MIDDLE AGED; NEOPLASM METASTASIS; PROTEIN KINASE INHIBITORS; QUINAZOLINES; RECEPTOR, ERBB-2; SURVIVAL ANALYSIS; TREATMENT OUTCOME; TUMOR MARKERS, BIOLOGICAL;

EID: 84868191989     PISSN: 01676806     EISSN: 15737217     Source Type: Journal    
DOI: 10.1007/s10549-012-2126-1     Document Type: Article

References (41)

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) GLOBOCAN 2008 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. International Agency for Research on Cancer. http://globocan. iarc.fr. Accessed 4 July 2011
2. Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ (2011) Strategies for subtypes-dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 22(8):1736-1747. doi:10.1093/annonc/mdr304
3. Perou CM, Sorlie T, Eisen MB, Van De Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406(6797):747-752. doi:10.1038/35021093
4. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, Van De Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Eystein Lonning P, Borresen-Dale AL (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98(19):10869-10874. doi:10.1073/pnas.191367098
5. Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lonning PE, Brown PO, Borresen-Dale AL, Botstein D (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100(14):8418-8423. doi:10.1073/pnas.0932692100
6. Biganzoli E, Coradini D, Ambrogi F, Garibaldi JM, Lisboa P, Soria D, Green AR, Pedriali M, Piantelli M, Querzoli P, Demicheli R, Boracchi P, Nenci I, Ellis IO, Alberti S (2011) p53 status identifies two subgroups of triple-negative breast cancers with distinct biological features. Jpn J Clin Oncol 41(2):172-179. doi:10.1093/jjco/hyq227
7. Ueno NT, Zhang D (2011) Targeting EGFR in triple negative breast cancer. J Cancer 2:324-328
8. Gluz O, Liedtke C, Gottschalk N, Pusztai L, Nitz U, Harbeck N (2009) Triple-negative breast cancer-current status and future directions. Ann Oncol 20(12):1913-1927. doi:10.1093/annonc/mdp492
9. Rodriguez-Pinilla SM, Sarrio D, Honrado E, Moreno-Bueno G, Hardisson D, Calero F, Benitez J, Palacios J (2007) Vimentin and laminin expression is associated with basal-like phenotype in both sporadic and BRCA1-associated breast carcinomas. J Clin Pathol 60(9):1006-1012. doi:10.1136/jcp. 2006.042143
10. Sarrio D, Rodriguez-Pinilla SM, Hardisson D, Cano A, Moreno-Bueno G, Palacios J (2008) Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype. Cancer Res 68(4):989-997. doi:10.1158/0008-5472. CAN-07-2017
11. Teng YH, Tan WJ, Thike AA, Cheok PY, Tse GM, Wong NS, Yip GW, Bay BH, Tan PH (2011) Mutations in the epidermal growth factor receptor (EGFR) gene in triple negative breast cancer: possible implications for targeted therapy. Breast Cancer Res 13(2):R35. doi:10.1186/bcr2857
12. Baselga J, Gomez P, Awada A, Greil R, Braga S, Climent MA, Wardley A, Zubel A, Groos J, Kaufmann B (2010) The addition of cetuximab to cisplatin increases overall response rate (ORR) and progression-free survival (PFS) in metastatic triple-negative breast cancer (TNBC): results of a randomized phase II study (BALI-1). Ann Oncol 21(Suppl. 8): viii96 (abstract 274O)
13. Foley J, Nickerson NK, Nam S, Allen KT, Gilmore JL, Nephew KP, Riese DJ II (2010) EGFR signaling in breast cancer: bad to the bone. Semin Cell Dev Biol 21(9):951-960. doi:10.1016/j.semcdb.2010.08.009
14. Schiff R, Massarweh S, Shou J, Bharwani L, Arpino G, Rimawi M, Osborne C (2005) Advanced concepts in estrogen receptor biology and breast cancer endocrine resistance: implicated role of growth factor signaling and estrogen receptor coregulators. Cancer Chemother Pharmacol 56(Suppl 1):10-20. doi:10.1007/s00280-005-0108-2
15. Li D, Ambrogio L, Shimamura T, Kubo S, Takahashi M, Chirieac LR, Padera RF, Shapiro GI, Baum A, Himmelsbach F, Rettig WJ, Meyerson M, Solca F, Greulich H, Wong KK (2008) BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene 27(34):4702-4711. doi:10.1038/onc.2008.109
16. Willmarth NE, Ethier SP (2006) Autocrine and juxtacrine effects of amphiregulin on the proliferative, invasive, and migratory properties of normal and neoplastic human mammary epithelial cells. J Biol Chem 281(49):37728-37737. doi:10.1074/jbc. M60 6532200
17. Harbeck N, Schmidt M, Harter P, Possinger K, Jonat W, Lück H-J, Beckmann M, Fasching P, Schütte J, Solca F, Uttenreuther-Fischer M, Taton M, Lahogue A, Awada A, De Grève J, Canon JL, Dirix L, Fleischer F, Neven P, Gottschalk N, Piccart M, Schuler M (2009) BIBW 2992, a novel irreversible EGFR/HER1 and HER2 tyrosine kinase inhibitor for the treatment of patients with HER2-negative metastatic breast cancer after failure of no more than two prior chemotherapies. Cancer Res 69(Suppl 3): abstract (and poster) 5062
18. Corkery B, Crown J, Clynes M, O'Donovan N (2009) Epidermal growth factor receptor as a potential therapeutic target in triplenegative breast cancer. Ann Oncol 20(5):862-867. doi:10.1093/annonc/mdn710
19. Bates NP, Hurst HC (1997) An intron 1 enhancer element mediates oestrogen-induced suppression of ERBB2 expression. Oncogene 15(4):473-481. doi:10.1038/sj.onc.1201368
20. Newman SP, Bates NP, Vernimmen D, Parker MG, Hurst HC (2000) Cofactor competition between the ligand-bound oestrogen receptor and an intron 1 enhancer leads to oestrogen repression of ERBB2 expression in breast cancer. Oncogene 19(4):490-497. doi:10.1038/sj.onc.1203416
21. Yarden RI, Wilson MA, Chrysogelos SA (2001) Estrogen suppression of EGFR expression in breast cancer cells: a possible mechanism to modulate growth. J Cell Biochem Suppl 36:232-246
22. Harvey JM, Clark GM, Osborne CK, Allred DC (1999) Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 17(5):1474-1481
23. Gehan EA (1961) The determinatio of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. J Chronic Dis 13:346-353
24. Curigliano G, Goldhirsch A (2011) The triple-negative subtype: new ideas for the poorest prognosis breast cancer. J Natl Cancer Inst Monogr 43:108-110. doi:10.1093/jncimonographs/lgr038
25. Rastelli F, Biancanelli S, Falzetta A, Martignetti A, Casi C, Bascioni R, Giustini L, Crispino S (2010) Triple-negative breast cancer: current state of the art. Tumori 96(6):875-888
26. Hirsh V (2011) Managing treatment-related adverse events associated with EGFR tyrosine kinase inhibitors in advanced nonsmall-cell lung cancer. Curr Oncol 18(3):126-138
27. Hartmann JT, Haap M, Kopp HG, Lipp HP (2009) Tyrosine kinase inhibitors-a review on pharmacology, metabolism and side effects. Curr Drug Metab 10(5):470-481
28. Oakman C, Pestrin M, Zafarana E, Cantisani E, Di Leo A (2010) Role of lapatinib in the first-line treatment of patients with metastatic breast cancer. Cancer Manag Res 2:13-25
29. Green MD, Francis PA, Gebski V, Harvey V, Karapetis C, Chan A, Snyder R, Fong A, Basser R, Forbes JF (2009) Gefitinib treatment in hormone-resistant and hormone receptor-negative advanced breast cancer. Ann Oncol 20(11):1813-1817. doi:10.1093/annonc/mdp202
30. Zhang D, La Fortune TA, Krishnamurthy S, Esteva FJ, Cristofanilli M, Liu P, Lucci A, Singh B, Hung MC, Hortobagyi GN, Ueno NT (2009) Epidermal growth factor receptor tyrosine kinase inhibitor reverses mesenchymal to epithelial phenotype and inhibits metastasis in inflammatory breast cancer. Clin Cancer Res 15(21):6639-6648. doi:10.1158/1078-0432. CCR-09-0951
31. McGowan PM, Mullooly M, Sukor S, O'Donovan N, Duffy MJ (2010) ADAM17: a new therapeutic target for triple negative breast cancer? Presented at EORTC-NCI-AACR 2010, Poster number 129
32. Oliveras-Ferraros C, Vazquez-Martin A, Lopez-Bonet E, Martin-Castillo B, Del Barco S, Brunet J, Menendez JA (2008) Growth and molecular interactions of the anti-EGFR antibody cetuximab and the DNA cross-linking agent cisplatin in gefitinib-resistant MDA-MB-468 cells: new prospects in the treatment of triplenegative/basal-like breast cancer. Int J Oncol 33(6):1165-1176
33. Finn RS, Press MF, Dering J, Arbushites M, Koehler M, Oliva C, Williams LS, Di Leo A (2009) Estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2(HER2), and epidermal growth factor receptor expression and benefit from lapatinib in a randomized trial of paclitaxel with lapatinib or placebo as first-line treatment in HER2-negative or unknown metastatic breast cancer. J Clin Oncol 27(24):3908-3915. doi:10.1200/JCO.2008.18.1925
34. Carey LA, Rugo HS, Marcom PK, Irvin W, Ferraro M, Burrows E, He X, Perou CM, Winer EP, on behalf of the Translational Breast Cancer Research Consortium (2008) TBCRC 001: EGFR inhibition with cetuximab added to carboplatin in metastatic triple-negative (basal-like) breast cancer. J Clin Oncol 26(Suppl 15S): abstract 1009
35. O'Shaughnessy J, Weckstein DJ, Vukeelja SJ, McIntyre K, Krekow L, Holmes FA, Asmar L, Blum JL (2007) Preliminary results of a randomized phase II study of weekly irinotecan/carboplatin with or without cetuximab in patients with metastatic breast cancer. Breast Cancer Res Treat 106(Suppl 1):S32 (abstract 308)
36. O'Shaughnessy J, Schwartzberg LS, Danso MA, Rugo HS, Miller K, Yardley DA, Carlson RW, Finn RS, Charpentier E, Freese M, Gupta S, Blackwood-Chirchir A, Winer EP (2011) A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC). J Clin Oncol 29(Suppl 15S): abstract 1007
37. Carey LA, O'Shaughnessy JA, Hoadley K, Khambata-Ford S, Horak CE, Xu LA, Awad M, Brickman D, Muller S, Donato J, Asmar L, Stiljeman I, Ebbert M, Bernard P, Perou C (2009) Potential predictive markers of benefit from cetuximab in metastatic breast cancer: an analysis of two randomized Phase 2 trials. Cancer Res 69(Suppl 3):596S (abstract 2014)
38. Agus DB, Terlizzi E, Stopfer P, Amelsberg A, Gordon MS (2006) A phase I dose escalation study of BIBW 2992, an irreversible dual EGFR/HER2 receptor tyrosine kinase inhibitor, in a continuous schedule in patients with advanced solid tumours. J Clin Oncol 24(Suppl 18S): abstract 2074
39. Eskens FA, Mom CH, Planting AS, Gietema JA, Amelsberg A, Huisman H, Van Doorn L, Burger H, Stopfer P, Verweij J, De Vries EG (2008) A phase I dose escalation study of BIBW 2992, an irreversible dual inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) tyrosine kinase in a 2-week on, 2-week off schedule in patients with advanced solid tumours. Br J Cancer 98(1):80-85. doi:10.1038/sj.bjc.6604108
40. Lewis N, Marshall J, Amelsberg A, Cohen RB, Stopfer P, Hwang J, Malik S (2006) A phase I dose escalation study of BIBW 2992, an irreversible dual EGFR/HER2 receptor tyrosine kinase inhibitor, in a 3 week on 1 week off schedule in patients with advanced solid tumors. J Clin Oncol 24(Suppl 18S): abstract 3091
41. Yap TA, Vidal L, Adam J, Stephens P, Spicer J, Shaw H, Ang J, Temple G, Bell S, Shahidi M, Uttenreuther-Fischer M, Stopfer P, Futreal A, Calvert H, De Bono JS, Plummer R (2010) Phase I trial of the irreversible EGFR and HER2 kinase inhibitor BIBW 2992 in patients with advanced solid tumors. J Clin Oncol 28(25):3965-3972. doi:10.1200/JCO.2009.26.7278