There have been reports of noninfectious pneumonitis (including some with pulmonary hypertension as a secondary event), infections, and renal failure (including acute renal failure) in patients...
In advanced HR+, HER2-negative breast cancer, the mTOR pathway may contribute to endocrine resistance and disease progression.1-6
mTOR pathway hyperactivation may render endocrine therapy ineffective7-11
In HR+, HER2-negative aBC, only AFINITOR inhibits the mTOR pathway11
Inhibition of the mTOR pathway can counter tumor escape and may restore sensitivity to hormone therapy11,12
Play the video below and learn more about targeting the mTOR pathway with AFINITOR.
This video will take you through the role of the mTOR pathway with AFINITOR plus exemestane in HR+, HER2-negative breast cancer.
AI, aromatase inhibitor; CDK, cyclin-dependent kinase; ER, estrogen receptor; ERD, estrogen-receptor downregulator; G1, gap 1; G2, gap 2; M, mitosis; mTOR, mammalian target of rapamycin; P, phosphorylation; PI3K, phosphoinositide 3-kinase; Rb, retinoblastoma; S, synthesis; S6K1, p70 ribosomal S6 kinase 1; SERM, selective estrogen receptor modulator.
*Letrozole or anastrozole.
References: 1. Johnston SRD. New strategies in estrogen receptor-positive breast cancer. Clin Cancer Res. 2010;16(7):1979-1987. 2. Yamamoto-Ibusuki M, Arnedos M, André F. Targeted therapies for ER+/HER2- metastatic breast cancer. BMC Med. 2015;13:137. 3. Laplante M, Sabatini DM. mTOR signaling at a glance. J Cell Sci. 2009;122:3589-3594. 4. Azab SS. Targeting the mTOR signaling pathways in breast cancer: more than the rapalogs. J Biochem Pharmacol Res. 2013;1(2):75-83. 5. Yuan R, Kay A, Berg WJ, Lebwohl D. Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy. J Hematol Oncol. 2009;2:45. 6. Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell. 2006;124:471-484. 7. Miller TW, Rexer BN, Garrett JT, Arteaga CL. Mutations in the phosphatidylinositol 3-kinase pathway: role in tumor progression and therapeutic implications in breast cancer. Breast Cancer Res. 2011;13(6):224. 8. Di Cosimo S, Baselga J. Management of breast cancer with targeted agents: importance of heterogeneity. Nat Rev Clin Oncol. 2010;7(3):139-147. 9. Miller TW, Hennessy BT, González-Angulo AM, et al. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer. J Clin Invest. 2010;120(7):2406-2413. 10. Cavazzoni A, Bonelli MA, Fumarola C, et al. Overcoming acquired resistance to letrozole by targeting the PI3K/AKT/mTOR pathway in breast cancer cell clones. Cancer Lett. 2012;323(1):77-87. 11. Afinitor [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2018. 12. Ciruelos Gil EM. Targeting the PI3K/AKT/mTOR pathway in estrogen receptor-positive breast cancer. Cancer Treat Rev. 2014;40(7):862-871. 13. Exemestane [prescribing information]. New York, NY: Pfizer Inc.; 2016.
AFINITOR is indicated for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer in combination with exemestane after failure of treatment with letrozole or anastrozole.
Important Safety Information
AFINITOR is contraindicated in patients with clinically significant hypersensitivity to everolimus or to other rapamycin derivatives.
Severe Hypersensitivity Reactions
Angioedema With Concomitant Use of Angiotensin-Converting Enzyme (ACE) Inhibitors
Impaired Wound Healing
Risk of Infection or Reduced Immune Response With Vaccinations
Please see full Prescribing Information.