Dacomitinib

Dacomitinib – Targeted Therapy for EGFR+ NSCLC

What is Dacomitinib?

Dacomitinib, sold under the brand names Vizimpro® and Daconib, is an FDA-approved oral tyrosine kinase inhibitor (TKI) used as first-line treatment for EGFR mutation-positive metastatic non-small cell lung cancer (NSCLC). It selectively and irreversibly binds to EGFR exon 19 deletions or exon 21 L858R substitutions to block cancer cell growth.

Pronunciation: da-koh-mih-tih-nib
Drug Class: Second-generation irreversible EGFR TKI
Modality: Small Molecule

Indications

Dacomitinib is prescribed for:

  • Locally advanced or metastatic NSCLC with confirmed EGFR exon 19 deletions or exon 21 (L858R) mutations

  • It is not suitable for patients whose tumors harbor the T790M resistance mutation (osimertinib is preferred here)

Off-label research:

There is preliminary evidence for its use in epithelial ovarian cancer, though this requires further clinical validation.

Mechanism of Action

Dacomitinib is a second-generation EGFR inhibitor that:

  • Irreversibly binds to the ATP-binding site of EGFR, HER2, and HER4

  • Blocks phosphorylation of receptor proteins

  • Inhibits downstream signaling pathways that promote cancer cell survival and proliferation

This leads to:

  • Decreased tumor growth

  • Apoptosis (programmed cancer cell death)

  • Reduced resistance from EGFR mutations (partial action against T790M)

Dosage and Administration

  • Usual Dose: 45 mg orally once daily

  • Form: Oral tablet

  • With or without food

  • Do not crush or chew

  • Take at the same time daily

💡 Important: Never change your dose or stop treatment without consulting your healthcare provider.

Side Effects

⚠️ Common Side Effects (≥10% of patients):

Side Effect Management
Mouth sores/ulcers Use mouthwash, avoid acidic foods, keep hydrated
Loss of appetite & weight loss Nutritional support, dietitian referral
Nausea/Vomiting Anti-nausea meds, small meals
Diarrhea Antidiarrheal agents, fluid intake
Skin rash / acne Topical treatments, avoid harsh skincare products
Hair loss Temporary, regrows post-treatment
Nail inflammation (paronychia) Topical antibiotic creams
Hand-foot syndrome Use urea-based moisturizers, avoid hot water
Dry/red eyes Artificial tears or ophthalmic solutions

⚠️ Occasional Side Effects (1–10%):

  • Taste changes

  • Extra hair growth

  • Dehydration

  • Shortness of breath or interstitial lung disease (ILD)

Contact your doctor immediately if you experience lung symptoms, severe diarrhea, or vision changes.

Clinical Pharmacology and Pharmacodynamics

  • IC50 (L858R/T790M cell lines): ~280 nM

  • Activity: Inhibits phosphorylation and cell viability in EGFR-mutant models

  • Half-life: ~70 hours

  • Metabolism: Primarily hepatic via CYP2D6

  • Elimination: Feces (79%) and urine (3%)

ARCHER 1050 (Phase III Trial)

  • Compared with Gefitinib

  • Median progression-free survival (PFS): 14.7 months (Dacomitinib) vs. 9.2 months (Gefitinib)

  • Overall response rate: ~75%

  • Improved overall survival and durability of response

Precautions

Fertility:

  • Unknown effects on fertility

  • Discuss fertility preservation with your oncologist

Pregnancy & Contraception:

  • Category D: May harm a fetus

  • Use effective contraception during treatment and for 2 months after stopping therapy

Breastfeeding:

  • Not recommended due to possible drug transmission through breast milk

Drug Interactions

  • Avoid grapefruit and grapefruit juice

  • May interact with:

    • CYP2D6 inhibitors or inducers

    • Other EGFR inhibitors

    • Certain antibiotics and antifungals

Always inform your doctor about all medications, herbal supplements, and OTC drugs.

Monitoring

Required tests before and during therapy:

  • Liver and kidney function tests

  • Complete blood count (CBC)

  • Electrolytes & liver enzymes

  • EGFR mutation testing (FDA-approved companion diagnostic)

Immunizations & Medical Procedures

  • Avoid live vaccines during and for 12 months after treatment

    • Examples: MMR, BCG, yellow fever

  • Flu and COVID-19 vaccines are generally safe

Inform any healthcare provider or dentist about your cancer therapy before undergoing procedures or vaccinations.

Final Thoughts

Dacomitinib is a powerful first-line oral treatment for EGFR+ NSCLC. With its targeted, irreversible inhibition of EGFR pathways, it offers extended survival in selected patients. Always follow your oncologist’s advice, monitor side effects closely, and maintain routine follow-ups.

FAQs

Q1: Is Dacomitinib a chemotherapy drug?
No. It’s a targeted therapy, not traditional chemotherapy. It blocks specific molecular targets (EGFR) in cancer cells.

Q2: Can I stop taking Dacomitinib if I feel better?
No. Never stop without consulting your oncologist. Cancer may progress if therapy is discontinued prematurely.

Q3: How long do I take Dacomitinib?
As long as it’s effective and side effects are manageable.

Q4: What if I miss a dose?
Take it as soon as you remember unless it’s close to your next dose. Never double-dose.

Q5: Can I take Dacomitinib with food?
Yes. It can be taken with or without food.