Afatinib
Afatinib is an oral irreversible ErbB family blocker used to treat certain adults with locally advanced or metastatic non-small cell lung cancer (NSCLC).
Source:
EMA
Active Ingredients:
Indications
Representation
No sex-specific representation data
Efficacy
No sex-specific efficacy data
Posology
No sex-specific posology data
Potential Side Effects
No sex-specific potential side effect data
Sex- and gender-specific information
Men
Women
Disease prevalence by sex
62.8%
37.2%
Clinical study participation by sex
35-38%
62-65%
Representation Gap
No sex-specific data
-27.8% to -24.8%
+24.8% to +27.8%
Sex-specific efficacy/accuracy
No sex-specific data
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.
Sex-specific posology
No sex-specific data
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.
Sex-specific differences in possible side effects
No sex-specific data
Male patients do not have a specifically increased adverse reaction risk attributed to sex, whereas increased risk of diarrhoea, rash/acne and stomatitis is described mainly for female, low body-weight or renally impaired patients; no sex-stratified incidence rates are provided.
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.
Pregnancy / lactation
N / A
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.
Sex-specific non-clinical findings
After correction for body weight, female patients have approximately 15% higher steady-state afatinib exposure than males, which is associated with an increased risk of gastrointestinal and skin toxicities and warrants closer monitoring; non-clinical studies showed effects on reproductive organs at higher exposures, so a potential impact on fertility in both sexes 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.
Disease prevalence by sex
Men
62.8%
Women
37.2%
Clinical study participation by sex
Men
35-38%
Women
62-65%
Representation Gap
No sex-specific data
Men
-27.8% to -24.8%
Women
+24.8% to +27.8%
Sex-specific efficacy/accuracy
No sex-specific data
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.
Sex-specific posology
No sex-specific data
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.
Sex-specific differences in possible side effects
No sex-specific data
Men
Male patients do not have a specifically increased adverse reaction risk attributed to sex, whereas increased risk of diarrhoea, rash/acne and stomatitis is described mainly for female, low body-weight or renally impaired patients; no sex-stratified incidence rates are provided.
Women
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.
Pregnancy / lactation
Men
N / A
Women
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.
Sex-specific non-clinical findings
Men
After correction for body weight, female patients have approximately 15% higher steady-state afatinib exposure than males, which is associated with an increased risk of gastrointestinal and skin toxicities and warrants closer monitoring; non-clinical studies showed effects on reproductive organs at higher exposures, so a potential impact on fertility in both sexes cannot be excluded.
Women
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.
General information
General Efficacy
Not reported
General Posology
Not reported
Further Dose Adjustments
Not reported
Possible Side Effects
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).
Contraindications
Not reported
Clinical Trial Type and Population
Not reported
Representation
No sex-specific representation data
Efficacy
No sex-specific efficacy data
Posology
No sex-specific posology data
Potential Side Effects
No sex-specific potential side effect data
Sex- and gender-specific information
Men
Women
Disease prevalence by sex
62.8%
37.2%
Clinical study participation by sex
84%
16%
Representation Gap
No sex-specific data
+21.2%
-21.2%
Sex-specific efficacy/accuracy
No sex-specific data
In advanced squamous NSCLC previously treated with platinum-based chemotherapy, afatinib improved progression-free survival versus erlotinib with accompanying improvements in disease-related symptoms and quality of life; no clinically relevant sex-specific differences in efficacy were reported.
In advanced squamous NSCLC after platinum-based chemotherapy, afatinib improved progression-free survival versus erlotinib and was associated with better symptom control and quality of life; no clinically relevant sex-specific differences in efficacy were reported.
Sex-specific posology
No sex-specific data
For adults with squamous NSCLC, the standard dosing is 40 mg afatinib orally once daily on an empty stomach, continued until disease progression or intolerance; dose may be increased to 50 mg once daily in well-tolerated patients or interrupted and reduced in 10 mg steps to manage toxicity.
The dosing regimen for women with squamous NSCLC is the same as for men: 40 mg afatinib orally once daily on an empty stomach, with possible escalation to 50 mg if well tolerated or interruption and 10 mg stepwise reductions based on adverse reactions.
Sex-specific differences in possible side effects
No sex-specific data
In the squamous NSCLC setting, there is no specific signal of increased adverse reaction risk unique to male patients; an increased likelihood of diarrhoea, rash/acne and stomatitis is described predominantly for female, low body-weight or renally impaired patients, without quantitative sex-stratified rates.
Female sex, especially when combined with low body weight or renal impairment, is associated with higher afatinib exposure and an increased likelihood of diarrhoea, rash/acne and stomatitis, though no sex-specific incidence rates for these events are reported in the squamous NSCLC trial.
Pregnancy / lactation
N / A
For women of childbearing potential with squamous NSCLC, effective contraception is recommended during afatinib therapy and for at least 1 month after the last dose; as an EGFR-targeting agent, afatinib may harm the fetus and should be avoided during pregnancy unless the potential benefit clearly outweighs the risk, and women becoming pregnant should be informed about possible fetal hazards. Because afatinib is excreted in animal milk and is likely present in human milk, breastfeeding should be discontinued during treatment; non-clinical findings of reproductive organ toxicity at higher doses mean a possible impact on fertility cannot be excluded.
Sex-specific non-clinical findings
Sex-related pharmacokinetic analyses show that, after body-weight correction, female patients have higher afatinib exposure than males, which is linked to an increased risk of gastrointestinal and skin toxicities and underlies recommendations for closer monitoring in at-risk groups; non-clinical toxicology identified effects on reproductive organs at higher doses, suggesting a possible fertility impact in both sexes.
In non-clinical and pharmacokinetic evaluations, women had higher body-weight–corrected afatinib exposure than men, which correlates with greater risk of gastrointestinal and skin toxicities and justifies closer monitoring in at-risk female patients; animal studies showed reproductive organ toxicity at higher doses, so a potential impact on fertility in both sexes cannot be ruled out.
Disease prevalence by sex
Men
62.8%
Women
37.2%
Clinical study participation by sex
Men
84%
Women
16%
Representation Gap
No sex-specific data
Men
+21.2%
Women
-21.2%
Sex-specific efficacy/accuracy
No sex-specific data
Men
In advanced squamous NSCLC previously treated with platinum-based chemotherapy, afatinib improved progression-free survival versus erlotinib with accompanying improvements in disease-related symptoms and quality of life; no clinically relevant sex-specific differences in efficacy were reported.
Women
In advanced squamous NSCLC after platinum-based chemotherapy, afatinib improved progression-free survival versus erlotinib and was associated with better symptom control and quality of life; no clinically relevant sex-specific differences in efficacy were reported.
Sex-specific posology
No sex-specific data
Men
For adults with squamous NSCLC, the standard dosing is 40 mg afatinib orally once daily on an empty stomach, continued until disease progression or intolerance; dose may be increased to 50 mg once daily in well-tolerated patients or interrupted and reduced in 10 mg steps to manage toxicity.
Women
The dosing regimen for women with squamous NSCLC is the same as for men: 40 mg afatinib orally once daily on an empty stomach, with possible escalation to 50 mg if well tolerated or interruption and 10 mg stepwise reductions based on adverse reactions.
Sex-specific differences in possible side effects
No sex-specific data
Men
In the squamous NSCLC setting, there is no specific signal of increased adverse reaction risk unique to male patients; an increased likelihood of diarrhoea, rash/acne and stomatitis is described predominantly for female, low body-weight or renally impaired patients, without quantitative sex-stratified rates.
Women
Female sex, especially when combined with low body weight or renal impairment, is associated with higher afatinib exposure and an increased likelihood of diarrhoea, rash/acne and stomatitis, though no sex-specific incidence rates for these events are reported in the squamous NSCLC trial.
Pregnancy / lactation
Men
N / A
Women
For women of childbearing potential with squamous NSCLC, effective contraception is recommended during afatinib therapy and for at least 1 month after the last dose; as an EGFR-targeting agent, afatinib may harm the fetus and should be avoided during pregnancy unless the potential benefit clearly outweighs the risk, and women becoming pregnant should be informed about possible fetal hazards. Because afatinib is excreted in animal milk and is likely present in human milk, breastfeeding should be discontinued during treatment; non-clinical findings of reproductive organ toxicity at higher doses mean a possible impact on fertility cannot be excluded.
Sex-specific non-clinical findings
Men
Sex-related pharmacokinetic analyses show that, after body-weight correction, female patients have higher afatinib exposure than males, which is linked to an increased risk of gastrointestinal and skin toxicities and underlies recommendations for closer monitoring in at-risk groups; non-clinical toxicology identified effects on reproductive organs at higher doses, suggesting a possible fertility impact in both sexes.
Women
In non-clinical and pharmacokinetic evaluations, women had higher body-weight–corrected afatinib exposure than men, which correlates with greater risk of gastrointestinal and skin toxicities and justifies closer monitoring in at-risk female patients; animal studies showed reproductive organ toxicity at higher doses, so a potential impact on fertility in both sexes cannot be ruled out.
General information
General Efficacy
Not reported
General Posology
Not reported
Further Dose Adjustments
Not reported
Possible Side Effects
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).
Contraindications
Not reported
Clinical Trial Type and Population
Not reported
EQUAL CARE® Evaluations
EQUAL CARE® Evaluation
Medication
Source
Source:
EMA
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Prevalence Source: