In EGFR mutation-positive, locally advanced/metastatic NSCLC, afatinib significantly prolonged progression-free survival versus platinum-based chemotherapy and improved disease-related symptoms and quality of life; no clinically relevant sex-specific differences in efficacy were reported.

For adults, the recommended starting dose is 40 mg afatinib orally once daily on an empty stomach, continued until disease progression or unacceptable toxicity; the dose may be increased to 50 mg once daily in well-tolerated patients or reduced in 10 mg steps (e.g. to 30 mg then 20 mg) with treatment interruptions to manage adverse reactions.

No sex-based change to starting dose is recommended for women, but they have higher afatinib exposure and, especially if they have low body weight or renal impairment, a higher risk of toxicity, so standard dose-interruption and 10 mg stepwise reductions should be applied promptly with closer monitoring.

Women, particularly those with low body weight or renal impairment, have higher afatinib exposure and are at increased risk of diarrhoea, rash/acne and stomatitis, although quantitative sex-stratified adverse event rates are not reported.

The most frequent adverse reactions were diarrhoea and skin-related events, as well as stomatitis and paronychia. In clinical trials, very common adverse reactions (≥10%) with GIOTRIF 40 mg once daily included diarrhoea (up to 95%), stomatitis/mucosal inflammation (about 65–70%), rash and dermatitis acneiform (about 60–80%), paronychia (11–58%), decreased appetite, nausea, vomiting, dry skin, pruritus, epistaxis, cheilitis and weight decreased. Liver enzyme elevations (ALT/AST) occurred mainly as transient laboratory abnormalities. Serious but less frequent adverse reactions included interstitial lung disease (ILD)-like events (overall 0.7%, with about 0.5% grade ≥3), hepatic failure including fatalities in <1% of patients, gastrointestinal perforation (0.2% across randomized trials, sometimes fatal), bullous, blistering and exfoliative skin reactions including rare cases suggestive of Stevens-Johnson syndrome and toxic epidermal necrolysis, pancreatitis, renal impairment/failure, and keratitis or ulcerative keratitis. Dose reductions due to adverse reactions were common, and treatment discontinuations due to diarrhoea and rash/acne occurred in a small proportion of patients (up to approximately 3.8% and 2.0% respectively in LUX-Lung 8).

For women of childbearing potential, effective contraception is recommended during afatinib treatment and for at least 1 month after the last dose; afatinib, like other EGFR inhibitors, may cause fetal harm and should be avoided in pregnancy unless the expected benefit justifies the potential risk, and women becoming pregnant should be counselled about possible fetal hazards. Because afatinib is excreted in animal milk and is likely present in human milk, breastfeeding should be stopped during therapy; non-clinical studies showed effects on reproductive organs at higher doses, so an adverse effect on fertility cannot be excluded.

Female patients have approximately 15% higher body-weight–corrected steady-state afatinib exposure than males, which is associated with an increased risk of gastrointestinal and skin toxicities and underpins the recommendation for closer monitoring; non-clinical toxicology studies demonstrated effects on reproductive organs at higher doses, so a potential effect on fertility in both sexes cannot be excluded.