Randomized phase III placebo-controlled trial of letrozole plus oral temsirolimus as first-line endocrine therapy in postmenopausal women with locally advanced or metastatic breast cancer

Journal of Clinical Oncology

Volumn 31, Issue 2, 2013, Pages 196-202

  Wolff, Antonio C ^a   Lazar, Ann A ^b   Bondarenko, Igor ^c   Garin, August M ^d   Brincat, Stephen ^e   Chow, Louis ^f   Sun, Yan ^g   Neskovic Konstantinovic, Zora ^h   Guimaraes, Rodrigo C ⁱ   Fumoleau, Pierre ^j   Chan, Arlene ^l   Hachemi, Soulef ^k   Strahs, Andrew ^k   Cincotta, Maria ^k   Berkenblit, Anna ^k   Krygowski, Mizue ^k   Kang, Lih Lisa ^k   Moore, Laurence ^k   Hayes, Daniel F ^m  

^a JOHNS HOPKINS UNIVERSITY   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c Dnipropetrovsk State Medical Academy   (Ukraine)

^d Russian Oncology Center   (Russian Federation)

^e Sir Paul Boffa Hospital   (Malta)

^f UNIMED Medical Institute   (Hong Kong)

^g CANCER HOSPITAL   (China)

^h INSTITUTE FOR ONCOLOGY AND RADIOLOGY OF SERBIA   (Serbia)

ⁱ HOSPITAL VERA CRUZ   (Brazil)

^j CENTRE GEORGES FRANÇOIS LECLERC   (France)

^k PFIZER INC   (United States)

^l Mount Medical Center   (Australia)

^m UNIVERSITY OF MICHIGAN COMPREHENSIVE CANCER CENTER   (United States)

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Author keywords

[No Author keywords available]

Indexed keywords

ADVERSE DRUG REACTION; ANTINEOPLASTIC AGENT; DRUG ADMINISTRATION; DRUG DERIVATIVE; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ESTROGEN RECEPTOR; LETROZOLE; NITRILE; PLACEBO; PROGESTERONE RECEPTOR; RAPAMYCIN; TEMSIROLIMUS; TRIAZOLE DERIVATIVE;

ABDOMINAL PAIN; ADULT; ADVANCED CANCER; AGE; AGED; ANEMIA; ANOREXIA; ARTHRALGIA; ARTICLE; ASTHENIA; BACKACHE; BREAST CANCER; BREAST TUMOR; CANCER ADJUVANT THERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER HORMONE THERAPY; CANCER PATIENT; CANCER SURVIVAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; COUGHING; DIARRHEA; DISEASE FREE SURVIVAL; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG THERAPY; DRUG WITHDRAWAL; DYSPNEA; EXPLORATORY RESEARCH; FEMALE; FEVER; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; HEADACHE; HUMAN; HYPERCHOLESTEROLEMIA; HYPERGLYCEMIA; HYPERLIPIDEMIA; INFECTION; KARNOFSKY PERFORMANCE STATUS; LUNG EMBOLISM; MAJOR CLINICAL STUDY; METASTASIS; MIDDLE AGED; MUCOSA INFLAMMATION; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; ORAL DRUG ADMINISTRATION; OVERALL SURVIVAL; PAIN; PATHOLOGY; PHASE 3 CLINICAL TRIAL; PNEUMONIA; POSTMENOPAUSE; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; RASH; RESPIRATORY FAILURE; SIDE EFFECT; STOMATITIS; TREATMENT DURATION; TREATMENT FAILURE; TREATMENT OUTCOME; TREATMENT RESPONSE; TREATMENT WITHDRAWAL; VASODILATATION; VERY ELDERLY; VOMITING;

ADMINISTRATION AND DOSAGE; ADMINISTRATION, ORAL; ADULT; ADVERSE EFFECTS; AGED; AGED, 80 AND OVER; ANALOGS AND DERIVATIVES; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BREAST NEOPLASMS; DISEASE-FREE SURVIVAL; DOUBLE-BLIND METHOD; DRUG THERAPY; FEMALE; HUMANS; MIDDLE AGED; NEOPLASM METASTASIS; NITRILES; PATHOLOGY; PLACEBOS; POSTMENOPAUSE; SIROLIMUS; TREATMENT OUTCOME; TRIAZOLES;

IM; MLCS; MLOWN; NLM;

EID: 84872518645     PISSN: 0732183X     EISSN: 15277755     Source Type: Journal    
DOI: 10.1200/JCO.2011.38.3331     Document Type: Article

References (27)

1. Goss PE, Strasser K: Tamoxifen resistant and refractory breast cancer: The value of aromatase inhibitors. Drugs 62:957-966, 2002 (Pubitemid 34454621)
2. Leary AF, Sirohi B, Johnston SR: Clinical trials update: Endocrine and biological therapy combinations in the treatment of breast cancer. Breast Cancer Res 9:112, 2007
3. Miller WR, Bartlett J, Brodie AM, et al: Aromatase inhibitors: Are there differences between steroidal and nonsteroidal aromatase inhibitors and do they matter? Oncologist 13:829-837, 2008
4. Dowsett M, Cuzick J, Ingle J, et al: Metaanalysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol 28:509-518, 2010
5. Smith IE, Dowsett M: Aromatase inhibitors in breast cancer. N Engl J Med 348:2431-2442, 2003 (Pubitemid 36682823)
6. 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 60:5887-5894, 2000
7. deGraffenried LA, Friedrichs WE, Russell DH, et al: Inhibition of mTOR activity restores tamoxifen response in breast cancer cells with aberrant Akt Activity. Clin Cancer Res 10:8059-8067, 2004 (Pubitemid 39587547)
8. Tokunaga E, Kimura Y, Mashino K, et al: Activation of PI3K/Akt signaling and hormone resistance in breast cancer. Breast Cancer 13:137-144, 2006
9. Carpenter JT, Roché H, Campone M, et al: Randomized 3-arm, phase 2 study of temsirolimus (CCI-779) in combination with letrozole in postmenopausal women with locally advanced or metastatic breast cancer. J Clin Oncol 23:19s, 2005 (suppl 16; abstr 564)
10. Hutcheson IR, Knowlden JM, Madden TA, et al: Oestrogen receptor-mediated modulation of the EGFR/MAPK pathway in tamoxifen-resistant MCF-7 cells. Breast Cancer Res Treat 81:81-93, 2003 (Pubitemid 37108443)
11. Johnston SR: Clinical efforts to combine endocrine agents with targeted therapies against epidermal growth factor receptor/human epidermal growth factor receptor 2 and mammalian target of rapamycin in breast cancer. Clin Cancer Res 12: 1061s-1068s, 2006 (Pubitemid 43259844)
12. Rudolf J, Boulay A, Zumstein-Mecker S, et al: The mTOR pathway in estrogen response: A potential for combining the rapamycin derivative RAD001 with the aromatase inhibitor letrozole in breast carcinomas. Proc Am Assoc Cancer Res 45, 2004 (abstr A5619)
13. Witters L, Engle L, Lipton A: Restoration of estrogen responsiveness by blocking the HER-2/neu pathway. Oncol Rep 9:1163-1166, 2002
14. Chan S, Scheulen ME, Johnston S, et al: Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. J Clin Oncol 23:5314-5322, 2005 (Pubitemid 46206985)
15. Therasse P, Arbuck SG, Eisenhauer EA, et al: New guidelines to evaluate the response to treatment in solid tumors: European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205-216, 2000
16. Kaplan EL, Meier P: Nonparametric estimation from incomplete observation. J Am Stat Assoc 53:457-481, 1958
17. Bonetti M, Zahrieh D, Cole BF, et al: A small sample study of the STEPP approach to assessing treatment-covariate interactions in survival data. Stat Med 28:1255-1268, 2009
18. Lazar AA, Cole BF, Bonetti M, et al: Evaluation of treatment-effect heterogeneity using biomarkers measured on a continuous scale: Subpopulation treatment effect pattern plot. J Clin Oncol 28:4539-4544, 2010
19. Baselga J, Campone M, Piccart M, et al: Everolimus in postmenopausal hormone-receptor- positive advanced breast cancer. N Engl J Med 366:520-529, 2012
20. Fleming GF, Ma CX, Huo D, et al: Phase II trial of temsirolimus in patients with metastatic breast cancer. Breast Cancer Res Treat [epub ahead of print on January 13, 2012]
21. Courtney KD, Corcoran RB, Engelman JA: The PI3K pathway as drug target in human cancer. J Clin Oncol 28:1075-1083, 2010
22. Yu K, Toral-Barza L, Discafani C, et al: mTOR, a novel target in breast cancer: The effect of CCI- 779, an mTOR inhibitor, in preclinical models of breast cancer. Endocr Relat Cancer 8:249-258, 2001 (Pubitemid 32947647)
23. Chu IM, Hengst L, Slingerland JM: The Cdk inhibitor p27 in human cancer: Prognostic potential and relevance to anticancer therapy. Nat Rev Cancer 8:253-267, 2008 (Pubitemid 351430863)
24. McShane LM, Altman DG, Sauerbrei W, et al: Reporting recommendations for tumor marker prognostic studies (REMARK). J Natl Cancer Inst 97: 1180-1184, 2005 (Pubitemid 41258223)
25. Hudes G, Carducci M, Tomczak P, et al: Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271-2281, 2007 (Pubitemid 46849157)
26. Tam VC, Tannock IF, Massey C, et al: Compendium of unpublished phase III trials in oncology: Characteristics and impact on clinical practice. J Clin Oncol 29:3133-3139, 2011
27. Hayes DF: Clinical trials: The silent minority- Unpublished data on cancer care. Nat Rev Clin Oncol 8:631-632, 2011.