trif excluded patients with an abnormal left ventricular ejection fraction (LVEF), i.e., below the institutional lower limit of normal. In Study 1, all patients were eva luated for LVEF at screening and every 9 weeks thereafter in the Gilotrif-treated group and as needed in the pemetrexed/cisplatin group. More Gilotrif-treated patients (2.2%; n=5) experienced ventricular dysfunction (defined as diastolic dysfunction, left ventricular dysfunction, or ventricular dilation; all < Grade 3) compared to chemotherapy-treated patients (0.9%; n=1).
Table 1 Adverse Reactions Reported in ≥10% of Gilotrif-Treated Patients in Study 1
Gilotrif
n=229 Pemetrexed/Cisplatin
n=111
Adverse Reaction All Grades
(%) Grade 3*
(%) All Grades
(%) Grade 3*
(%)
Gastrointestinal disorders
Diarrhea 96 15 23 2
Stomatitis1 71 9 15 1
Cheilitis 12 0 1 0
Skin and subcutaneous tissue disorders
Rash/Dermatitis acneiform2 90 16 11 0
Pruritus 21 0 1 0
Dry skin 31 0 2 0
Infections and infestations
Paronychia3 58 11 0 0
Cystitis 13 1 5 0
Metabolism and nutrition disorders
Decreased appetite 29 4 55 4
Respiratory, thoracic and mediastinal disorders
Epistaxis 17 0 2 1
Rhinorrhea 11 0 6 0
Investigations
Weight Investigations 17 1 14 1
General disorders and administration site conditions
Pyrexia 12 0 6 0
Eye disorders
Conjunctivitis 11 0 3 0
None of the adverse reactions in this table were Grade 4 in severity
1Includes stomatitis, aphthous stomatitis, mucosal inflammation, mouth ulceration, oral mucosa erosion, mucosal erosion, mucosal ulceration
2Includes group of rash preferred terms, acne, acne pustular, dermatitis acneiform
3Includes paronychia, nail infection, nail bed infection
Table 2 Adverse Reactions of Laboratory Abnormalities from the Investigations SOC Reported in ≥5% of Gilotrif-Treated Patients in Study 1 1Includes hypokalemia, blood potassium decreased
SOC=system organ class
Gilotrif
n=229 Pemetrexed/Cisplatin
n=111
Adverse Reaction All Grades
(%) Grades 3-4
(%) All Grades
(%) Grades 3-4
(%)
Alanine aminotransferase increased 11 2 4 0
Hypokalemia1 11 4 5 4
Aspartate aminotransferase increased 8 2 2 1
Includes hypokalemia, blood potassium decreased
SOC=system organ class
7 DRUG INTERACTIONS
Effect of P-glycoprotein (P-gp) Inhibitors and Inducers
Oral administration of a P-gp inhibitor (ritonavir at 200 mg twice daily) 1 hour before administration of Gilotrif increased systemic exposure to afatinib by 48%. There was no change in afatinib exposure when ritonavir was administered simultaneously with or 6 hours after Gilotrif. Concomitant taking of P-gp inhibitors (including but not limited to ritonavir, |
