Summary of the safety profile: In the pooled dataset from the ISEL, INTEREST and IPASS phase III clinical trials (2462 gefitinib-treated patients), the most frequently reported adverse drug reactions (ADRs), occurring in more than 20% of the patients, are diarrhoea and skin reactions (including rash, acne, dry skin and pruritus). ADRs usually occur within the first month of therapy and are generally reversible.
Approximately 8% of patients had a severe ADR (common toxicity criteria, (CTC) grade 3 or 4). Approximately 3% of patients stopped therapy due to an ADR.
Interstitial lung disease (ILD) has occurred in 1.3% of patients, often severe (CTC grade 3-4). Cases with fatal outcomes have been reported.
Tabulated list of adverse reactions: The safety profile presented in Table 7 is based on the gefitinib clinical development programme and postmarketed experience. Adverse reactions have been assigned to the frequency categories in Table 7 where possible based on the incidence of comparable adverse event reports in a pooled dataset from the ISEL, INTEREST and IPASS phase III clinical trials (2462 gefitinib-treated patients).
Frequencies of occurrence of undesirable effects are defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. (See Table 7.)
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Interstitial lung disease (ILD): In the INTEREST trial, the incidence of ILD type events was 1.4% (10) patients in the gefitinib group versus 1.1% (8) patients in the docetaxel group. One ILD-type event was fatal, and this occurred in a patient receiving gefitinib.
In the ISEL trial, the incidence of ILD-type events in the overall population was approximately 1% in both treatment arms. The majority of ILD-type events reported was from patients of Asian ethnicity and the ILD incidence among patients of Asian ethnicity receiving gefitinib therapy and placebo was approximately 3% and 4% respectively. One ILD-type event was fatal, and this occurred in a patient receiving placebo.
In a post-marketing surveillance study in Japan (3350 patients) the reported rate of ILD-type events in patients receiving gefitinib was 5.8%. The proportion of ILD-type events with a fatal outcome was 38.6%.
In a phase III open-label clinical trial (IPASS) in 1217 patients comparing gefitinib to carboplatin/paclitaxel doublet chemotherapy as first-line treatment in selected patients with advanced NSCLC in Asia, the incidence of ILD-type events was 2.6% on the gefitinib treatment arm versus 1.4% on the carboplatin/paclitaxel treatment arm.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.