Lucius Version of Dacomitinib: Dosage and Administration, Indications, Precautions

Lucius Version of Dacomitinib: Dosage and Administration, Indications, Precautions

Indications

Dacomitinib is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.

Dosage and Administration

The recommended dose is 45 mg orally once daily until disease progression or unacceptable toxicity occurs.

It can be taken with or without food.

Mechanism of Action

Dacomitinib is an irreversible inhibitor of the kinase activity of the human EGFR family (EGFR/HER1, HER2, and HER4) and certain EGFR-activating mutations (exon 19 deletions or exon 21 L858R substitution mutations). At clinically relevant concentrations, dacomitinib also inhibits the activities of DDR1, EPHA6, LCK, DDR2, and MNK1 in vitro.

In mice bearing subcutaneous xenografts of human tumors driven by mutated EGFR family (HER family) targets, dacomitinib exhibits dose-dependent inhibition of EGFR and HER2 autophosphorylation as well as tumor growth. Dacomitinib also demonstrates antitumor activity in mice with intracranial human tumor xenografts driven by EGFR amplification following oral administration.

Efficacy and Safety

A phase III clinical trial was conducted in patients with locally advanced or metastatic NSCLC harboring EGFR gene mutations. The results showed that the median overall survival (mOS) of patients treated with dacomitinib was 34.1 months, meaning half of the patients survived for more than 34.1 months.In contrast, the mOS of patients treated with gefitinib was 26.8 months, representing a 7-month extension with dacomitinib. Regarding median progression-free survival (mPFS), dacomitinib yielded a mPFS of 14.7 months (i.e., half of the patients experienced no disease progression for over 14.7 months), compared with 9.2 months for gefitinib.

For patients with exon 19 deletions, the mPFS was 14.6 months in the dacomitinib group versus 9.6 months in the erlotinib group. In terms of overall survival comparison, the dacomitinib group achieved 26.6 months versus 24.2 months in the erlotinib group.

Use in Special Populations

Lactation: Breastfeeding is not recommended during treatment with dacomitinib.

Adverse Reactions

The most common adverse reactions (incidence > 20%) are diarrhea, rash, paronychia, stomatitis, decreased appetite, dry skin, weight loss, alopecia, cough, and pruritus.

Precautions

Interstitial Lung Disease (ILD): Permanently discontinue dacomitinib if ILD is confirmed.

Diarrhea: Withhold and reduce the dose of dacomitinib based on the severity of the condition.

Dermatologic Adverse Reactions: Withhold and reduce the dose of dacomitinib based on the severity of the reactions.

Embryo-Fetal Toxicity: Dacomitinib can cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment.

Drug Interactions

Proton Pump Inhibitors (PPIs): Avoid concomitant use with dacomitinib. Use locally acting antacids or H2-receptor antagonists instead. Administer dacomitinib at least 6 hours before or 10 hours after H2-receptor antagonists.

CYP2D6 Substrates: Avoid concomitant use with dacomitinib for CYP2D6 substrates where even a minimal increase in substrate concentrations may lead to severe or life-threatening toxicity.

Contraindications

Not yet established.

Dosage Form

Tablets.

Storage Conditions

Store at 20°C to 25°C (68°F to 77°F); short-term transportation is permitted at temperatures ranging from 15°C to 30°C (59°F to 86°F).