Afatinib (Gilotrif)

A targeted therapy approved for use in the treatment of metastatic nonsmall-cell lung cancer (NSCLC) that tests positive for epidermal growth-factor receptor mutations (EGFRm+).

A companion diagnostic test, the Therascreen EGFR is available.

About 10% to 15% of NSCLC is EGFRm+ in Western populations.

Deletion exon 19 makes up approximately 49% of the EGFR mutations.

EGFR mutation exon 21 (L858R) makes up 40% of the EGFR mutations in non small cell lung cancer.

The incidence of the mutation is higher in Asian populations.

A tyrosine kinase inhibitor indicated for the first line treatment of patients with metastatic non-small cell lung cancer whose tumors have epidermal growth factor receptor exon 19 deletions or exon 21 (L858R) substitution mutations.

The LUX-Lung 3 study involved 345 patients with stage 3/4 lung adenocarcinoma that had tested positive for EGFR mutations who had not previously received chemotherapy.

In the LUX-Lung study patients were randomized in a 2:1 ratio to receive afatinib 40 mg daily or standard chemotherapy with cisplatin 75 mg/m² and pemetrexed 500 mg/m² intravenously every 21 days for up to 6 cycles: Median progression-free survival was better with afatinib than with chemotherapy (11.1 vs 6.9 months; hazard ratio, 0.58; P = .0004).

Updated data on the LUX- Lung 3 study there was a median PFS for afatinib of 13.6 months versus pemetrexed/cisplatin of 6.9 months.

Afatinib significantly improves outcomes in treatment naïve patients with EGFR mutated NSCLC compared with geftinib (LUX-Lung7 trial).

Disease control is comparable to and might be even better than the other targeted agents, and the adverse-effect profile appears to be less toxic.

Associated with a significantly prolonged overall survival in patients with exon 19 deletion compared with chemotherapy, but not with exon 21 mutations.

Preferered agent for patients with exon 19 deletions.

Dose 40 mg/day orally.

Common adverse effects of afatinib include diarrhea, skin rash that resemble acne, dry skin, pruritus, inflammation of the mouth, paronychia, decreased appetite, decreased weight, cystitis, nose bleed, runny nose, fever, eye inflammation, and hypokalemia.

Associated with high incidences of rash and diarrhea.

Specifically, diarrhea and rash of all grades were reported in 96% and 90% of patients treated with afatinib, respectively.

Paronychia of all grades occurred in 58% of patients.

Elevated ALT of all grades was seen in 11% of patients.

Approximately 1.5% of patients treated with afatinib across clinical trials had interstitial lung diseases.

Serious adverse effects include diarrhea that can result in kidney failure, severe dehydration, severe rash, lung inflammation, and liver toxicity.

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