or patients treated with pemetrexed/cisplatin. The overall trial population had a median age of 61 years; 61% of patients in the GILOTRIF arm and 60% of patients in the pemetrexed/cisplatin arm were younger than 65 years. A total of 64% of patients on GILOTRIF and 67% of pemetrexed/cisplatin patients were female. More than two-thirds of patients were from Asia (GILOTRIF 70%; pemetrexed/cisplatin 72%).
Serious adverse reactions were reported in 29% of patients treated with GILOTRIF. The most frequent serious adverse reactions reported in patients treated with GILOTRIF were diarrhea (6.6%); vomiting (4.8%); and dyspnea, fatigue, and hypokalemia (1.7% each). Fatal adverse reactions in GILOTRIF-treated patients in Study 1 included pulmonary toxicity/ILD-like adverse reactions (1.3%), sepsis (0.43%), and pneumonia (0.43%).
Dose reductions due to adverse reactions were required in 57% of GILOTRIF-treated patients. The most frequent adverse reactions that led to dose reduction in the patients treated with GILOTRIF were diarrhea (20%), rash/acne (19%), paronychia (14%), and stomatitis (10%).
Discontinuation of therapy in GILOTRIF-treated patients for adverse reactions was 14.0%. The most frequent adverse reactions that led to discontinuation in GILOTRIF-treated patients were diarrhea (1.3%), ILD (0.9%), and paronychia (0.9%).
Clinical trials of GILOTRIF 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 *None of the adverse reactions in this table were Grade 4 in severity1 Includes stomatitis, aphthous stomatitis, mucosal inflammation, mouth ulceration, oral mucosa erosion, mucosal erosion, mucosal ulceration2 Includes group of rash preferred terms, acne, acne pustular, dermatitis acneiform3 Includes paronychia, nail infection, nail bed infection
GILOTRIFn=229 Pemetrexed/Cisplatinn=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
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