Everolimus: Targeted therapy on the horizon for the treatment of breast cancer

Pharmacotherapy

Volumn 32, Issue 4, 2012, Pages 383-396

  Barnett, Chad M ^a  

^a UNIVERSITY OF TEXAS   (United States)

Author keywords

Breast cancer; Everolimus; Mammalian target of rapamycin; MTOR

Indexed keywords

AMPRENAVIR; ATAZANAVIR; CISPLATIN; CLARITHROMYCIN; CYCLOPHOSPHAMIDE; EPIRUBICIN; ERYTHROMYCIN; EVEROLIMUS; FLUOROURACIL; FOSAMPRENAVIR; FULVESTRANT; INDINAVIR; ITRACONAZOLE; KETOCONAZOLE; LAPATINIB; LETROZOLE; NAVELBINE; NEFAZODONE; NELFINAVIR; PACLITAXEL; PLACEBO; RITONAVIR; SAQUINAVIR; TAMOXIFEN; TELITHROMYCIN; TRASTUZUMAB; UNINDEXED DRUG; VERAPAMIL; VORICONAZOLE; ZOLEDRONIC ACID; DRUG DERIVATIVE; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ESTROGEN RECEPTOR; HER2 PROTEIN, HUMAN; IMMUNOSUPPRESSIVE AGENT; MTOR PROTEIN, HUMAN; RAPAMYCIN; TARGET OF RAPAMYCIN KINASE;

ABNORMAL LABORATORY RESULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALOPECIA; ANEMIA; ANOREXIA; AREA UNDER THE CURVE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; ASTHENIA; BREAST CANCER; CANCER CELL CULTURE; CANCER CHEMOTHERAPY; CANCER HORMONE THERAPY; CANCER SURVIVAL; CELL PROLIFERATION; CREATININE BLOOD LEVEL; DIARRHEA; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG ERUPTION; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENTIATION; DRUG SAFETY; DRUG TOLERABILITY; ESTROGEN RECEPTOR POSITIVE BREAST CANCER; FATIGUE; FEBRILE NEUTROPENIA; GASTROINTESTINAL SYMPTOM; HEMATOLOGIC DISEASE; HEPATOBILIARY DISEASE; HUMAN; HYPERCHOLESTEROLEMIA; HYPERGLYCEMIA; HYPOKALEMIA; INFECTION; LEUKOPENIA; LOADING DRUG DOSE; LYMPHOCYTOPENIA; LYMPHOMA; MAXIMUM PLASMA CONCENTRATION; METABOLIC DISORDER; MOLECULARLY TARGETED THERAPY; MONOTHERAPY; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; NAUSEA; NONHUMAN; PAIN; PNEUMONIA; PROGRESSION FREE SURVIVAL; PRURITUS; RESPIRATORY TRACT DISEASE; REVIEW; SEPSIS; SIDE EFFECT; SIGNAL TRANSDUCTION; SKIN DISEASE; STOMATITIS; THROMBOCYTOPENIA; THROMBOEMBOLISM; TIME TO MAXIMUM PLASMA CONCENTRATION; TREATMENT OUTCOME; TREATMENT RESPONSE; VOMITING; BREAST TUMOR; CLINICAL TRIAL (TOPIC); DRUG ANTAGONISM; DRUG INTERACTION; FEMALE; GENETICS; PHASE 3 CLINICAL TRIAL (TOPIC);

BREAST NEOPLASMS; CLINICAL TRIALS AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; DRUG INTERACTIONS; FEMALE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; RECEPTOR, ERBB-2; RECEPTORS, ESTROGEN; SIROLIMUS; TOR SERINE-THREONINE KINASES;

EID: 84864107018     PISSN: 02770008     EISSN: None     Source Type: Journal    
DOI: 10.1002/j.1875-9114.2012.01084.x     Document Type: Review

References (49)

1. American Cancer Society. Cancer facts and figures 2011. American Cancer Society, Atlanta, GA, 2011:1-60.
2. National Cancer Institute. SEER statistic fact sheet: breast cancer. National Cancer Institute, Available from: http://www.seer. cancer.gov/ statfacts/html/breast.html. Accessed February 28, 2012.
3. Germano S, O'Driscoll L. Breast cancer: understanding sensitivity and resistance to chemotherapy and targeted therapies to aid in personalised medicine. Current Cancer Drug Targets 2009;9:398-418.
4. Sheri A, Martin LA, Johnston S. Targeting endocrine resistance: is there a role for mTOR inhibition? Clin Breast Cancer 2010;10(suppl 3):S79-85.
5. De Martino MC, van Koetsveld PM, Pivonello R, Hofland LJ. Role of the mTOR pathway in normal and tumoral adrenal cells. Neuroendocrinology 2010;92(suppl 1):28-34.
6. Huang S, Houghton PJ. Targeting mTOR signaling for cancer therapy. Current Opinion in Pharmacology 2003;3:371-7.
7. Bjornsti MA, Houghton PJ. The TOR pathway: a target for cancer therapy. Nat Rev Cancer 2004;4:335-48.
8. Margariti N, Fox SB, Bottini A, Generali D. "Overcoming breast cancer drug resistance with mTOR inhibitors." Could it be a myth or a real possibility in the short-Term future? Breast Cancer Res Treat 2011;128:599-606.
9. Perez-Tenorio G, Alkhori L, Olsson B, et al. PIK3CA mutations and PTEN loss correlate with similar prognostic factors and are not mutually exclusive in breast cancer. Clin Cancer Res 2007;13:3577-84.
10. Shoman N, Klassen S, McFadden A, Bickis MG, Torlakovic E, Chibbar R. Reduced PTEN expression predicts relapse in patients with breast carcinoma treated by tamoxifen. Mod Pathol 2005;18:250-9.
11. Zhou X, Tan M, Stone HV, et al. Activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway by ErbB2 overexpression predicts tumor progression in breast cancers. Clin Cancer Res 2004;10:6779-88.
12. 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 2004;10:8059-67.
13. Musgrove EA, Sutherland RL. Biological determinants of endocrine resistance in breast cancer. Nat Rev Cancer 2009;9:631-43.
14. Chollet P, Abrial C, Tacca O, et al. Mammalian target of rapamycin inhibitors in combination with letrozole in breast cancer. Clin Breast Cancer 2006;7:336-8.
15. 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.
16. Harari D, Yarden Y. Molecular mechanisms underlying ErbB2/HER2 action in breast cancer. Oncogene 2000;19:6102-14.
17. Novartis Pharmaceuticals Corporation. AFINITOR (everolimus) tablets for oral administration package insert. Novartis Pharmaceuticals Corporation, East Hanover, NJ, 2011.
18. Wyeth Pharmaceuticals Inc. TORISEL Kit (temsirolimus) injection, for intravenous infusion only package insert. Wyeth Pharmaceuticals Inc, Philadelphia, PA, 2010.
19. Chow LWC, Sun Y, Jassem J, et al. Phase 3 study of temsirolimus with letrozole or letrozole alone in postmenopausal women with locally advanced or metastatic breast cancer. Presented at the 29th annual San Antonio breast cancer symposium, San Antonio, TX, December 14-17, 2006.
20. Bachelot T, Bourgier C, Cropet C, et al. TAMRAD: a GINECO randomized phase II trial of everolimus in combination with tamoxifen versus tamoxifen alone in patients (pts) with hormone-receptor positive, HER2 negative metastatic breast cancer (MBC) with prior exposure to aromatase inhibitors (AI). Presented at the 33rd annual San Antonio breast cancer symposium, San Antonio, TX, December 8-12, 2010.
21. Sabine VS, Sims AH, Macaskill EJ, et al. Gene expression profiling of response to mTOR inhibitor everolimus in preoperatively treated post-menopausal women with oestrogen receptor-positive breast cancer. Breast Cancer Res Treat 2010;122:419-28.
22. Lu CH, Wyszomierski SL, Tseng LM, et al. Preclinical testing of clinically applicable strategies for overcoming trastuzumab resistance caused by PTEN deficiency. Clin Cancer Res 2007;13:5883-8.
23. Lane H, Stephan C, Zumstein-Mecker S, et al. A potential for combining the mTOR inhibitor RAD001 (everolimus) with the ErbB2 receptor tyrosine kinase inhibitory antibody trastuzumab in breast cancer [abstract]. Eur J Cancer 2006;4:175.
24. Boulay A, Rudloff J, Ye J, et al. Dual inhibition of mTOR and estrogen receptor signaling in vitro induces cell death in models of breast cancer. Clin Cancer Res 2005;11:5319-28.
25. Rudloff J, Boulay A, Zumstein-Mecker S, Evans DB, O'Reilly T, Lane HA. The mTOR pathway in estrogen response: a potential for combining the rapamycin derivative RAD001 with the aromatase inhibitor letrozole in breat carninomas [abstract]. Proceedings of the American Association for Cancer Research 2004;45:A5619.
26. Treeck O, Wackwitz B, Haus U, Ortmann O. Effects of a combined treatment with mTOR inhibitor RAD001 and tamoxifen in vitro on growth and apoptosis of human cancer cells. Gynecol Oncol 2006;102:292-9.
27. Beeram M, Tan QT, Tekmal RR, Russell D, Middleton A, deGraffenried LA. Akt-induced endocrine therapy resistance is reversed by inhibition of mTOR signaling. Ann Oncol 2007;18:1323-8.
28. Kirchner GI, Meier-Wiedenbach I, Manns MP. Clinical pharmacokinetics of everolimus. Clin Pharmacokinet 2004;43:83-95.
29. Sanchez-Fructuoso AI. Everolimus: an update on the mechanism of action, pharmacokinetics and recent clinical trials. Expert Opinion on Drug Metabolism and Toxicology 2008;4:807-19.
30. Kovarik JM, Hartmann S, Figueiredo J, et al. Effect of food on everolimus absorption: quantification in healthy subjects and a confirmatory screening in patients with renal transplants. Pharmacotherapy 2002;22:154-9.
31. Kovarik JM, Sabia HD, Figueiredo J, et al. Influence of hepatic impairment on everolimus pharmacokinetics: implications for dose adjustment. Clin Pharmacol Ther 2001;70: 425-30.
32. Ellard SL, Clemons M, Gelmon KA, et al. Randomized phase II study comparing two schedules of everolimus in patients with recurrent/metastatic breast cancer: NCIC Clinical Trials Group IND.163. J Clin Oncol 2009;27:4536-41.
33. Maas N, Harbeck N, du Bois A, et al. RADAR: A randomized discontinuation phase II study to determine the efficacy of RAD001 (RAD) in breast cancer (BC) patients (pts) with bone metastases only (GBG41). Presented at the American Society of clinical oncology breast cancer symposium, San Francisco, CA, October 8-10, 2009.
34. Andre F, Campone M, O'Regan R, et al. Phase I study of everolimus plus weekly paclitaxel and trastuzumab in patients with metastatic breast cancer pretreated with trastuzumab. J Clin Oncol 2010;28:5110-5.
35. Jerusalem G, Fasolo A, Dieras V, et al. Phase I trial of oral mTOR inhibitor everolimus in combination with trastuzumab and vinorelbine in pre-Treated patients with HER2-overexpressing metastatic breast cancer. Breast Cancer Res Treat 2011;125:447-55.
36. Morrow PKH, Wulf GM, Ensor J, et al. Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy. J Clin Oncol 2011;29:3126-32.
37. Dalenc F, Campone M, Hupperets P, et al. Everolimus in combination with weekly paclitaxel and trastuzumab in patients (pts) with HER-2-overexpressing metastatic breast cancer (MBC) with prior resistance to trastuzumab and taxanes: a multicenter phase II clinical trial. Presented at the American Society of clinical oncology annual meeting, Chicago, IL, June 4-8, 2010.
38. Jerusalem G, Fasolo A, Massacesi C, et al. Maintenance with everolimus (RAD001) and trastuzumab (T) after discontinuation of chemotherapy in heavily pre-Treated HER-2 + metastatic breast cancer (MBC) patients (pts): pooled data of extension cohorts of phase Ib/II studies. Presented at the American Society of Clinical Oncology Annual Meeting, Chicago, IL, June 4-8, 2010.
39. Campone M, Gianni L, Massacesi C, et al. Trastuzumab (H) and everolimus (RAD001) containing regimens are safe and active when reintroduced in patients (pts) with HER2-overexpressing metastatic breast cancer (MBC) pre-Treated with lapatinib [abstract]. Eur J Cancer Suppl 2010;8:186.
40. Mayer IA, Burris H, Bendel J, et al. A phase Ib trial of RAD001, an mTOR inhibitor, with weekly cisplatin and paclitaxel in patients with HER2-negative metastatic breast cancer. Presented at the 32nd annual San Antonio breast cancer symposium, San Antonio, TX, December 9-13, 2009.
41. Gonzalez-Angulo A, Green MC, Murray JL, et al. Open label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC (T-FEC) vs the combination of paclitaxel and RAD001 followed by FEC (TR-FEC) in women with triple receptor-negative breast cancer (TNBC). Presented at the American Society of Clinical Oncology Annual Meeting, Chicago IL, June 3-7, 2011.
42. Awada A, Cardoso F, Fontaine C, et al. The oral mTOR inhibitor RAD001 (everolimus) in combination with letrozole in patients with advanced breast cancer: results of a phase I study with pharmacokinetics. Eur J Cancer 2008;44:84-91.
43. Badin F, Romond E, Chambers M, et al. A phase II trial of fulvestrant and RAD001 (everolimus) in patients with metastatic estrogen receptor positive breast cancer after aromatase inhibitor failure; a study in progress. Presented at the 33rd annual San Antonio breast cancer symposium, San Antonio, TX, December 8-12, 2010.
44. Baselga J, Semiglazov V, van DP, et al. Phase II randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancer. J Clin Oncol 2009;27:2630-7.
45. Alexandru S, Ortiz A, Baldovi S, et al. Severe everolimusassociated pneumonitis in a renal transplant recipient. Nephrol Dial Transplant 2008;23:3353-5.
46. Jerusalem G, Ellard SL, Fasolo A, et al. Non-infectious pneumonitis (NIP) in breast cancer (BC) patients (Pts) treated with Everolimus (AfinitorTM) containing therapy: analysis of five studies. Presented at the 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 9-13, 2009.
47. Campone M, Levy V, Bourbouloux E, et al. Safety and pharmacokinetics of paclitaxel and the oral mTOR inhibitor everolimus in advanced solid tumours. Br J Cancer 2009;100:315-21.
48. Moulder SL, Rivera E, Ensor J, et al. Phase I trial of escalating doses of weekly everolimus (RAD001) in combination with docetaxel for the treatment of metastatic breast cancer (MBC). Presented at the American Society of Clinical Oncology Annual Meeting, Orlando, FL, May 29-June 2, 2009.
49. Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2012;366:520-9.