nt becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)].
Advise females of reproductive potential to use highly effective contraception during treatment, and for at least 2 weeks after the last dose of Gilotrif. Advise patients to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, while taking Gilotrif [see Use in Specific Populations (8.1 and 8.6)].
6 ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the labeling:
•Diarrhea [see Warnings and Precautions (5.1)]
•Bullous and Exfoliative Skin Disorders [see Warnings and Precautions (5.2)]
•Interstitial Lung Disease [see Warnings and Precautions (5.3)]
•Hepatic Toxicity [see Warnings and Precautions (5.4)]
•Keratitis [see Warnings and Precautions (5.5)]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety eva luation of Gilotrif is based on the data from more than 3800 patients, including 2135 NSCLC patients receiving Gilotrif monotherapy at or above the recommended dose.
Controlled Study
The data in Tables 1 and 2 below reflect exposure of 229 EGFR-TKI naïve Gilotrif-treated patients with EGFR mutation-positive, metastatic, non-squamous, NSCLC enrolled in a randomized, multicenter, open-label trial (Study 1). Patients received Gilotrif 40 mg daily until documented disease progression or intolerance to the therapy. A total of 111 patients were treated with pemetrexed/cisplatin. Patients were treated with pemetrexed 500 mg/m² followed after 30 minutes by cisplatin 75 mg/m² every three weeks for a maximum of six treatment courses.
The median exposure was 11.0 months for patients treated with Gilotrif and 3.4 months for 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 Gilo |
