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Gilotrif ™ - afatinib

Gilotrif ™ - afatinib

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Gilotrif ™ - afatinib

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  1. Gilotrif™ - afatinib Manufacturer: Boehringer Ingelheim FDA Approval Date: July 2013

  2. Gilotrif™ - afatinibClinical Application • Indications: metastatic non-small cell lung cancer (NSCLC) • EGFR exon 19 deletions or exon 21 substitution mutations (L858R mutations) • Place in therapy: • First-line treatment for patients with EGFR mutations

  3. Gilotrif™ - afatinibClinical Application • Contraindications: None • Warning and Precautions • Dermatologic toxicity • GI toxicity • Hepatotoxicity • Ocular toxicity

  4. Gilotrif™ - afatinibClinical Application • Pregnancy: • Category D (positive evidence of human fetal risk) • Lactation: • Excretion in breast milk unknown; use caution

  5. Gilotrif™ - afatinibDrug Facts • Pharmacology: • Afatinib covalently and irreversibly binds to the intracellular tyrosine kinase domain of EGFR • This inhibits downstream signaling by EGFR resulting in tumor growth inhibition and tumor regression

  6. Gilotrif™ - afatinibDrug Facts • Pharmacokinetics: • A – Absorption is decreased with high fat meals. • D – Time to peak 2-5 hours • M – Minimal enzymatic metabolism • E – Primarily excreted via feces (85%)

  7. Gilotrif™ - afatinibDrug Interactions • Drug Interactions – Precipitant Drugs: • Pgp inhibitors: may need to reduce afatinib daily dose by 10 mg if concomitant therapy is not tolerated. • Pgp inducers: may need to increase afatinib daily dose by 10 mg if on chronic concomitant therapy with a Pgp inducer.

  8. Gilotrif™ - afatinibAdverse Effects • Diarrhea (95%) • Acneiform rash (89%) • Stomatitis (72%) • Paronychia (57%) • Dry skin (29%) • Pruritis (19%) • Weight loss (17%) • Epistaxis (17%) • Fever (12%) • Conjunctivitis (11%)

  9. Gilotrif™ - afatinibMonitoring Parameters • Efficacy Monitoring: • Disease progression • Cough, dyspnea, and pain • Toxicity Monitoring: • Skin toxicity • Signs/symptoms of dehydration

  10. Gilotrif™ - afatinibPrescription Information • Dosing: 40 mg once daily • Cost: Unknown at present • Launch date has not been released

  11. Gilotrif™ - afatinibLiterature Review • LUX-Lung III was a global, randomized, open-label study comparing first-line afatinib with cisplatin plus pemetrexed chemotherapy • Patients with advanced lung adenocarcinoma and proven EGFR mutations Sequist LV, et al. J Clin Oncol 2013; 31:1-11.

  12. Gilotrif™ - afatinibLiterature Review • Inclusion criteria • EGFR mutation • Treatment naïve • Good performance status • Adequate end-organ function • Measurable disease using RECIST Sequist LV, et al. J Clin Oncol 2013; 31:1-11.

  13. Gilotrif™ - afatinibLiterature Review • Demographics • 1,269 patients were screened and 345 patients were randomly assigned treatment • 72% Asian • 68% never-smokers • 65% women • 49% exon 19 deletions • 40% exon 21 (L858R) point mutations Sequist LV, et al. J Clin Oncol 2013; 31:1-11.

  14. Gilotrif™ - afatinibLiterature Review • Primary endpoint • Progression free survival (PFS) • Treatment (2:1) n=345 • Afatinib 40 mg once per day OR • IV cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 once every 21 days Sequist LV, et al. J Clin Oncol 2013; 31:1-11.

  15. Gilotrif™ - afatinibLiterature Review • Assessments • Tumor assessments were performed every 6 weeks for the first 48 weeks • Every 12 weeks thereafter until disease progression or the start of new anticancer therapy Sequist LV, et al. J Clin Oncol 2013; 31:1-11.

  16. Gilotrif™ - afatinibLiterature Review Sequist LV, et al. J Clin Oncol 2013; 31:1-11.

  17. Gilotrif™ - afatinibLiterature Review Sequist LV, et al. J Clin Oncol 2013; 31:1-11.

  18. Gilotrif™ - afatinibLiterature Review Sequist LV, et al. J Clin Oncol 2013; 31:1-11.

  19. Gilotrif™ - afatinibLiterature Review • Conclusions from LUX-Lung III • Afatinib significantly increases progression-free survival in NSCLC patients with EGFR mutations • Did not demonstrate overall survival benefit • Adverse effects were common Sequist LV, et al. J Clin Oncol 2013; 31:1-11.

  20. Gilotrif™ - afatinibSummary • Afatinib is approved for NSCLC patients with EGFR mutations • 40 mg daily and should be taken at least 1 hour before or 2 hours after a meal. • Diarrhea, acneiform rash, and stomatitis are common adverse effects • Afatinib demonstrated a significant increase in progression-free survival in the LUX-Lung III trial

  21. Gilotrif™ - afatinibReferences • http://www.gilotrif.com • Gilotrif package insert. Boehringer Ingelheim. July 2013. • Afatinib. Facts and Comparisons Online. Accessed October 1 2013. • Sequist LV, et al. Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma with EGFR Mutations. J Clin Oncol 2013; 31:1-11.