61
Views
0
CrossRef citations to date
0
Altmetric
Drug Evaluation

Everolimus-related adverse events in neuroendocrine tumors and comparative considerations with breast and renal cancer: a critical overview

, , &
Pages 525-536 | Received 20 Feb 2017, Accepted 22 May 2017, Published online: 31 May 2017

References

  • Motzer RJ, Escudier B, Oudard S, et al. Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer. 2010;116(18):4256–4265.
  • Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):514–523.
  • Yao JC, Fazio N, Singh S, et al. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet. 2016;387(10022):968–997.
  • Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor–positive advanced breast cancer. N Eng J Med. 2012;366(6):520–529.
  • Soefje SA, Karnad A, Brenner AJ. Common toxicities of mammalian target of rapamycin inhibitors. Target Oncol. 2011;6:125–129.
  • O’Reilly KE, Rojo F, She QB, et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res. 2006;66:1500–1508.
  • Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell. 2006;124:471–484.
  • Crowe A, Bruelisauer A, Duerr L, et al. Absorption and intestinal metabolism of SDZ-RAD and rapamycin in rats. Drug Metab Dispos. 1999;27:627–632.
  • Prescribing information. Afinitor (everolimus). East Hanover, NJ: Novartis Pharmaceuticals Corporation. 2012 Aug [cited 2017 Jan 15]. Available from: http://www.pharma.us.novartis.com/product/pi/pdf/afinitor.pdf
  • Jacobsen W, Serkova N, Hausen B, et al. Comparison of the in vitro metabolism of the macrolide immunosuppressants sirolimus and RAD. Transpl Proc. 2001;33:514–515.
  • Klumpen HJ, Beijnen JH, Gurney H, et al. Inhibitors of mTOR. Oncologist. 2010;15:1262–1269.
  • Kirchner GI, Meier-Wiedenbach I, Manns MP. Clinical pharmacokinetics of everolimus. Clin Pharmacokinet. 2004;43:83–95.
  • Kovarik JM, Sabia HD, Figueiredo J, et al. Influence of hepatic impairment on everolimus pharmacokinetics: implications for dose adjustment. Clin Pharmacol Ther. 2001;70:425–430.
  • Zhu AX, Kudo M, Assenat E, et al. Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial. Jama. 2014;321:57–67.
  • Picard N, Rouguieg-Malki K, Kamar N, et al. CYP3A5 genotype does not influence everolimus in vitro metabolism and clinical pharmacokinetics in renal transplant recipients. Transplantation. 2011;91:652–656.
  • Bowlin SJ, Xia F, Wang W, et al. Twelve-month frequency of drug-metabolizing enzyme and transporter-based drug-drug interaction potential in patients receiving oral enzyme-targeted kinase inhibitor antineoplastic agents. Mayo Clin Proc. 2013;88:139–148.
  • Kovarik JM, Hartmann S, Figueiredo J, et al. Effect of rifampin on apparent clearance of everolimus. Ann Pharmacother. 2002;36:981–985.
  • Lefeuvre S, Rebaudet S, Billaud EM, et al. Management of rifamycins-everolimus drug–drug interactions in a liver-transplant patient with pulmonary tuberculosis. Transpl Int. 2012;25:e120–3.
  • Kovarik JM, Beyer D, Bizot MN, et al. Blood concentrations of everolimus are markedly increased by ketoconazole. J Clin Pharmacol. 2005;45:514–518.
  • Kovarik JM, Hsu CH, McMahon L, et al. Population pharmacokinetics of everolimus in de novo renal transplant patients: impact of ethnicity and comedications. Clin Pharmacol Ther. 2001;70:247–254.
  • Kovarik JM, Beyer D, Bizot MN, et al. Effect of multiple-dose erythromycin on everolimus pharmacokinetics. Eur J Clin Pharmacol. 2005;61:35–38.
  • Kovarik JM, Beyer D, Bizot MN, et al. Pharmacokinetic interaction between verapamil and everolimus in healthy subjects. Br J Clin Pharmacol. 2005;60:434–437.
  • Molina AM, Feldman DR, Voss MH, et al. Phase 1 trial of everolimus plus sunitinib in patients with metastatic renal cell carcinoma. Cancer. 2012;118:1868–1876.
  • Harzstark AL, Small EJ, Weinberg VK, et al. A phase 1 study of everolimus and sorafenib for metastatic clear cell renal cell carcinoma. Cancer. 2011;117:4194–4200.
  • Deenen MJ, Klumpen HJ, Richel DJ, et al. Phase I and pharmacokinetic study of capecitabine and the oral mTOR inhibitor everolimus in patients with advanced solid malignancies. Invest New Drugs. 2012;30:1557–1565.
  • Morrow PK, 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;29:3126–3132.
  • Kovarik JM, Hartmann S, Hubert M, et al. Pharmacokinetic and pharmacodynamic assessments of hmg-coa reductase inhibitors when coadministered with everolimus. J Clin Pharmacol. 2002;42:222–228.
  • Grabowsky JA. Drug interactions and the pharmacist: focus on everolimus. Ann Pharmacother. 2013;47(7–8):1055–1063.
  • Nowack R. Review article: cytochrome P450 enzyme, and transport protein mediated herb-drug interactions in renal transplant patients: grapefruit juice, St John’s wort, and beyond! Nephrology. 2008;13:337–47.
  • Fleisher D, Li C, Zhou Y, et al. Drug, meal and formulation interactions influencing drug absorption after oral administration. Clinical implications. Clin Pharmacokinet. 1999;36:233–254.
  • Pavel ME, Hainsworth JD, Baudin E, et al. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet. 2011;378(9808):2005–2012.
  • Piccart M, Hortobagyi GN, Campone M, et al. Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2. Ann Oncol. 2014;25:2357–2362.
  • Martins F, De Oliveira MA, Wang Q, et al. A review of oral toxicity associated with mTOR inhibitor therapy in cancer patients. Oral Oncol. 2013;49:293–298.
  • Sonis S, Treister N, Chawla S, et al. Preliminary characterization of oral lesions associated with inhibitors of mammalian target of rapamycin in cancer patients. Cancer. 2010;116:210–215.
  • Boers-Doets CB, Raber-Durlacher JE, Treister NS, et al. Mammalian target of rapamycin inhibitor-associated stomatitis. Future Oncol. 2013;9:1883–1892.
  • Watters AL, Epstein JB, Agulnik M. Oral complications of targeted cancer therapies: a narrative literature review. Oral Oncol. 2011;47:441–448.
  • Sankhala K, Mita A, Kelly K, et al. The emerging safety profile of mTOR inhibitors, a novel class of anticancer agents. Target Oncol. 2009;4:135–142.
  • Pilotte AP, Hohos MB, Polson KM, et al. Managing stomatitis in patients treated with mammalian target of rapamycin inhibitors. Clin J Oncol Nurs. 2011;15:E83–9.
  • Rugo HS, Pritchard KI, Gnant M, et al. Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2. Ann Oncol. 2014;25:808–815.
  • De Oliveira MA, Martins E, Martins F, et al. Clinical presentation and management of mTOR inhibitor-associated stomatitis. Oral Oncol. 2011;47(10):998–1003.
  • Sessa C, Tosi D, Viganò L, et al. Phase Ib study of weekly mammalian target of rapamycin inhibitor ridaforolimus (AP23573; MK-8669) with weekly paclitaxel. Ann Oncol. 2010;21:1315–1322.
  • Grünwald V, Weikert S, Pavel ME, et al. Practical management of everolimus-related toxicities in patients with advanced solid tumors. Onkologie. 2013;36(5):295–302.
  • Boers-Doets C, Lalla RV. The mIAS scale: a scale to measure mTOR inhibitor-associated stomatitis. Supp. Care Cancer. 2013;21(Suppl.1):1–6.
  • Peterson DE, O’Shaughnessy JA, Rugo HS, et al. Oral mucosal injury caused by mammalian target of rapamycin inhibitors: emerging perspectives on pathobiology and impact on clinical practice. Cancer Med. 2016;5(8):1897–1907.
  • Hurvitz SA, Andre F, Jiang Z, et al. Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial. Lancet Oncol. 2015;16(7):816–829.
  • André F, O’Regan R, Ozguroglu M, et al. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014;15(6):580–591.
  • Motzer RJ, Barrios CH, Kim TM, et al. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014;32(25):2765–2772.
  • Verzoni E, Pusceddu S, Buzzoni R, et al. Safety profile and treatment response of everolimus in different solid tumors: an observational study. Future Oncol. 2014;10(9):1611–1617.
  • Ferté C, Paci A, Zizi M, et al. Natural history, management and pharmacokinetics of everolimus-induced-oral ulcers: insights into compliance issues. Eur J Cancer. 2011;47:2249–2255.
  • Morelon E, Stern M, Kreis H. Interstitial pneumonitis associated with sirolimus therapy in renal-transplant recipients. N Engl J Med. 2000;343:225–226.
  • Willemsen AE, Grutters JC, Gerritsen WR, et al. mTOR inhibitor-induced interstitial lung disease in cancer patients: comprehensive review and a practical management algorithm. Int J Cancer. 2016;138(10):2312–2321.
  • Feagans J, Victor D, Moehlen M, et al. Interstitial pneumonitis in the transplant patient: consider sirolimus-associated pulmonary toxicity. J La State Med Soc. 2009;161:166–172.
  • Pham PT, Pham PC, Danovitch GM, et al. Sirolimus associated pulmonary toxicity. Transplantation. 2004;77:1215–1220.
  • Nishino M, Brais LK, Brooks NV, et al. Drug-related pneumonitis during mammalian target of rapamycin inhibitor therapy in patients with neuroendocrine tumors: a radiographic pattern-based approach. Eur J Cancer. 2016;53:163–170.
  • Morelon E, Stern M, Israel-Biet D, et al. Characteristics of sirolimus associated interstitial pneumonitis in renal transplant patients. Transplantation. 2001;72:787–790.
  • Weiner SM, Sellin L, Vonend O, et al. Pneumonitis associated with sirolimus: clinical characteristics, risk factors and outcome–a single-centre experience and review of the literature. Nephrol Dial Transplant. 2007;22:3631–3637.
  • West ML. Bronchiolitis obliterans and organizing pneumonia in renal transplant recipients. Transplantation. 2000;69:1531–1532.
  • Motzer RJ, Escudier B, Oudard S, et al. RECORD‐1 Study Group. Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer. 2010;116(18):4256–4265.
  • Porta C, Osanto S, Ravaud A, et al. Management of adverse events associated with the use of everolimus in patients with advanced renal cell carcinoma. Eur J Cancer. 2011;47:1287–1298.
  • Dabydeen DA, Jagannathan JP, Ramaiya N, et al. Pneumonitis associated with mTOR inhibitors relation with clinical outcome. Eur J Cancer. 2012;48:1519–1524.
  • Iacovelli R, Palazzo A, Mezi S, et al. Incidence and risk of pulmonary toxicity in patients treated with mTOR inhibitors for malignancy. A meta- analysis of published trials. Acta Oncol. 2012;51:873–879.
  • Albiges L, Chamming’s F, Duclos B, et al. Incidence and management of mTOR inhibitor-associted pneumonitis in patients with metastatic renal cell carcinoma. Ann Oncol. 2012;23:1943–1953.
  • Rodriguez-Pascual J, Cheng E, Maroto P, et al. Emergent toxicities associated with the use of mTOR inhibitors in patients with advanced renal carcinoma. Anticancer Drugs. 2010;21:478–486.
  • Busaidy NL, Farooki A, Dowlati A, et al. Management of metabolic effects associated with anticancer agents targeting the PI3K-AKT-mTOR pathway. J Clin Oncol. 2012;30:2919–2928.
  • Leibiger IB, Leibiger B, Moede T, et al. Exocytosis of insulin promotes insulin gene transcription via the insulin receptor/PI-3 kinase/p70 s6 kinase and CaM kinase pathways. Mol Cell. 1998;1:933–938.
  • Fuhrer DK, Kobayashi M, Jiang H. Insulin release and suppression by tacrolimus, rapamycin and cyclosporin A are through regulation of the ATP- sensitive potassium channel. Diabetes Obes Metab. 2001;3:393–402.
  • Kulke MH, Bergsland EK, Yao JC. Glycemic control in patients with insulinoma treated with everolimus. N Engl J Med. 2009;360:195–197.
  • Peterson DE, Bensadoun RJ, Roila F. Management of oral and gastrointestinal mucositis: ESMO Clinical Practice Guidelines. Ann Oncol. 2011;22:78–84.
  • Vergès B, Walter T, Cariou B. Endocrine side effects of anti-cancer drugs: effects of anti-cancer targeted therapies on lipid and glucose metabolism. Eur J Endocrinol. 2014;170(2):43–55.
  • Nozawa M, Nonomura N, Ueda T, et al. Adverse event profile and dose modification of everolimus for advanced renal cell carcinoma in real-world Japanese clinical practice. Jpn J Clin Oncol. 2013;43(11):1132–1138.
  • Guo J, Huang Y, Zhang X, et al. Safety and efficacy of everolimus in Chinese patients with metastatic renal cell carcinoma resistant to vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy: an open-label phase 1b study. BMC Cancer. 2013;13(1):136.
  • Daniel C, Renders L, Amann K, et al. Mechanisms of everolimus-induced glomerulosclerosis after glomerular injury in the rat. Am J Transplant. 2005;5:2849–2861.
  • Pascual J. Everolimus in clinical practice–renal transplantation. Nephrol Dial Transplant. 2006;21(Suppl.3):18–23.
  • Shang YH, Zhang Y, Li JH, et al. Risk of endocrine adverse events in cancer patients treated with PD-1 inhibitors: a systematic review and meta-analysis. Immunotherapy. 2017;9(3):261–272.
  • Prichard KI, Ha Iii B, Ito Y, et al. Safety and efficacy of everolimus with exemestane vs. exemestane alone in elderly patients with HER2-negative. Hormone Receptor-Positive Breast Cancer in BOLERO-2. Clin Breast Cancer. 2013;13:421–432.
  • Porta C, Calvo E, Climent M, et al. Efficacy and safety of everolimus in elderly patients with metastatic renal cell carcinoma: an exploratory analysis of the outcomes of elderly patients in the RECORD-1 trial. Eur Urol. 2012;61:826–833.
  • Motzer RJ, Escudier B, Oudard S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008;372:449–456.
  • Noguchi S, Masuda N, Iwata H, et al. Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone-receptor-positive breast cancer in BOLERO-2. Breast Cancer. 2014;21:703–714.
  • Dabydeen DA, Jagannathan JP, Ramaiya N, et al. Pneumonitis associated with mTOR inhibitors therapy in patients with metastatic renal cell carcinoma: incidence, radiographic findings and correlation with clinical outcome. Eur J Cancer. 2012;48(10):19–24.
  • Albiges L, Caramella C, Ferte C, et al. Interstitial pneumonitis during RAD-001 treatment: incidence by blinded radiological analysis. Eur J Cancer Suppl. 2009;7:427.
  • Panzuto F, Rinzivillo M, Fazio N, et al. Real-world study of everolimus in advanced progressive neuroendocrine tumors. The Oncologist. 2014;19(9):966–974.
  • Bajetta E, Catena L, Fazio N, et al. Everolimus in combination with octreotide long-acting repeatable n a first-line setting for patients with neuroendocrine tumors: an ITMO group study. Cancer. 2014;120(16):2457–2463.
  • Aapro M, Andre F, Blackwell K, et al. Adverse event management in patients with advanced cancer receiving oral everolimus: focus on breast cancer. Ann Oncol. 2014;25(4):763–773.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.