Afatinib for metastatic non-small cell lung cancer

Afatinib (gilotrif) is a tyrosine kinase inhibitor that irreversibly inhibits EGFR (epidermal growth factor receptor).

It is used for the treatment of patients with metastatic NSCLC (non-small cell lung cancer).

It is indicated for the treatment of EGFR mutation-positive tumors. It is also indicated for the treatment of patients with metastatic squamous cell carcinoma (NSCLC) who have not responded to platinum-based chemotherapy.

Afatinib vs Cisplatin and pemetrexed chemotherapy:

Cisplatin-based chemotherapy regimen is considered as the optimal therapy for patients with NSCLC.
A study by V. Sequist et al compared afatinib with cisplatin and pemetrexed in patients with EGFR mutation-positive stage IIIB/IV lung adenocarcinoma.
The study showed a significant progression-free survival benefit and improvement in the symptoms of lung cancer treated with afatinib compared to cisplatin plus pemetrexed chemotherapy.
The treatment was well tolerated with few manageable adverse effects.

Afatinib versus cisplatin plus gemcitabine:

Another study compared afatinib with cisplatin + gemcitabine in Asian patients with advanced non-small-cell lung cancer harboring EGFR mutations.
The study showed significant improvements in the progression-free survival in Asian patients with EGFR mutation-positive advanced lung NSCLC with manageable adverse effects. (Ref).

Afatinib dosage in adults:

The usual dose is 40 mg once daily. If the dose is tolerated, it may be increased to 50 mg once daily after three weeks.

Dosage forms and strengths:

Tablets: 40 mg, 30 mg, and 20 mg.

Withhold GILOTRIF if any of the following any adverse reactions occur:

NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Grade 3 or higher
Diarrhea of grade 2 or higher that persists for two or more consecutive days while on anti-diarrheal medications.
SKin reactions of Grade 2 that are prolonged i.e. last more than seven days or are intolerable.

Dose in Children:

Not studied in children.

Pregnancy Category C

According to the labeling of the manufacturer, it should be avoided during pregnancy.
Women in reproductive age groups must be advised to use contraception during treatment, and for at least two weeks following the last dose.

Afatinib use in kidney disease:

Afatinib should be avoided in severe renal impairment.
The recommended dose of afatinib in patients with severe renal disease (eGFR of 15 to 29 ml/min) is 30 mg orally, once daily.

Afatinib use in liver disease:

Gilotrif should be avoided in severe liver disease.
In mild to moderate liver disease, it should be used with caution and symptoms and signs suggestive of hepatotoxicity should be monitored.

Afatinib side effects:

Acne,
conjunctivitis,
cystitis,
decreased appetite,
dehydration,
diarrhea,
dry eyes,
dry skin,
dyspepsia,
nose bleeds,
hand-foot syndrome,
electrolyte imbalance (hypokalemia),
muscle spasms,
paronychia,
pruritus,
pyrexia,
rash,
renal failure,
flu and rhinorrhoea,
weight loss,
Interstitial lung disease,
keratitis,
alopecia,
bone marrow suppression,
hyperuricemia,
nausea and vomiting,
oral mucositis,
thromboembolism
tumour lysis syndrome.

Important safety information

What to avoid while taking GILOTRIF

Limit your time in the sun.
Patients should be advised sunscreen, to wear a hat and cover the skin while taking Gilotrif to avoid sunburns and a rash.

GILOTRIF may cause severe side effects, including:

Diarrhea.

Diarrhea, sometimes severe leading to dehydration and renal failure is common with GILOTRIF.

Skin reactions.

GILOTRIF can cause redness, rash, blisters, acne and steven-johnsons syndrome.

Lung or breathing problems.

GILOTRIF may cause inflammation of the lung manifested by shortness of breath, cough, fever and chest pain that may lead to death. These symptoms may mimic primary lung disease.

Liver problems.

GILOTRIF is hepatotoxic and can cause serious liver disease leading to death.

Liver disease may be manifested by any of the following symptoms:

yellowing of your skin or the white part of your eyes (jaundice)
a dark or brown (tea-colored) urine
pain on the upper right side of your stomach area (abdomen)
bleeding or bruising more easily than normal
feeling very tired

Eye problems.
Gilotrif is toxic to the eyes as well. symptoms may include:
- eye pain, swelling, redness, or tearing
- blurred vision
- sensitivity to light
- other changes in your vision
Heart problems may occur with its use.
Patients may notice any of the following symptoms:
- new or worsening shortness of breath while at rest or with activity
- a cough
- tiredness
- swelling of your ankles, feet, or legs
- feeling that your heart is pounding or racing (palpitations)
- sudden weight gain

Contraindications and Cautions:

Patients suffering from heart disease and conditions that affect ejection fraction

At baseline and throughout treatment, cardiac monitoring should be considered, including assessment left ventricular ejection percentage.

Diarrhea:

It is recommended to take proactive measures. Avoid sun exposure History of keratitis.

New symptoms of a weakened lung (e.g., shortness or cough, fever, etc.):

Do not start treatment until interstitial pulmonary disease is eliminated.

Keratitis and severe dry eyes:

For a thorough assessment, consult immediately with an ophthalmologist.

Here are some signs and symptoms of a skin reaction.

If severe, Stevens-Johnson Syndrome suspected, or ulcerative keratitis, treat immediately and withhold afatinib.

Warnings and Precautions

Patients with Grade 2 or greater renal impairment should be advised to stop taking the drug until their renal function returns to normal or improves to Grade 1.
Reintroduce GILOTRIF at a dosage of 10 mg per daily less than that at which adverse reactions occurred.

Afatinib (Gilotrif) should be Permanently discontinued if:

Exfoliative, bullous, or blistering skin lesions can cause serious and life-threatening problems
Confirmed interstitial pulmonary disease (ILD).
Grave drug-induced liver disease
Persistent ulcerative Keratitis
Left ventricular dysfunction symptoms
At a daily dose of 20 mg, severe or intolerable adverse reactions can occur.

Monitor:

Monitor for a response to therapy.
For adverse reactions (see contraindications and side effects), monitor Renal function tests, liver function tests, eye examination, and pulmonary function tests.

How to administer afatinib (Gilotrif)?

Afatinib should be taken one hour before or two hours after a meal.
Following a fatty meal, its absorption decreases by 39%.

Afatinib Mechanism of action:

Afatinib, an irreversible inhibitor tyrosine kinase inhibitor, is used to treat EGFR mutants positive metastatic small cell.
It takes between 2 and 5 hours for plasma to reach peak concentration.
After 8 days, the steady-state plasma concentration is attained.

The half-life of the elimination is approximately 37 hours.

The majority of excretion occurs via the stomach (85% via the feces).