A new treatment approved for advanced lung cancer

The United States Food and Drug Administration (FDA) approved Afatinib (Gilotrif), offering hope for advanced non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations.

Cancer ranks second, after heart disease, among life-threatening diseases. Despite all scientific advances, data from 1974-2001 suggest that lung cancer continues to carry a risk of death. Approximately 20.000 people are diagnosed annually and more than approximately half of this proportion are at risk of death. In our country, lung cancer ranks first among men at %40 and fourth among women at %8. It is a widely known fact that smoking is the most important cause of lung cancer. Recent statistics in Turkey show smoking rates of %50 among men and %18 among women. Considering that smoking is thought to account for %85-90 of lung cancer cases, I believe that quitting smoking could make this proportion preventable.

EGFR mutations

The commonest lung cancer is non-small cell lung cancer. Approximately %85 are this type, and %16 of these patients carry EGFR mutations, mostly deletions or substitutions (exon 19 deletion or exon 21 L858R substitution).

EGFR is a protein found on the surface of many cancer cells that plays a role in cancer development. Blocking the EGFR pathway helps targeted therapy inhibit cancer growth. Treatments that target how this pathway works will allow greater progress in cancers carrying gene mutations.

Afatinib (Gilotrif) 

Afatinib (gilotrif) inhibits tyrosine kinase, blocking intracellular growth signaling. It benefits targeted treatment in EGFR-mutated patients (exon 19 deletion or exon 21 L858R substitution).

The study approved by the United States Food and Drug Administration (FDA) enrolled 345 patients with advanced non-small cell lung cancer carrying an EGFR mutation. For 21 days, some patients received 40 mg Afatinib (Gilotrif) daily, while others received standard combination chemotherapy (pemetrexed and cisplatin) at specified intervals.

Two study endpoints:

• Primary: Duration of disease control
• Secondary: Tumor response, overall survival and side effects

After approximately 8 months of observation, the duration of disease control with treatment was 4 months longer in patients treated with afatinib than in those receiving standard chemotherapy. Progression-free survival was extended to 11.1 months in patients given afatinib, while this period was determined to be 6.9 months in those receiving standard chemotherapy.

Afatinib benefited patients with deletion 19 or L858R EGFR mutations, or both, a group of 308 patients. The duration of disease control with treatment was extended to 13.6 months in patients treated with afatinib, compared with 6.9 months in those receiving standard chemotherapy, with survival almost doubling in afatinib users. In addition, quality of life improved compared with standard chemotherapy, and lung cancer symptoms such as shortness of breath and cough were observed not to worsen.

Most common effects

The study identified:

Skin reactions:

• Acne
• Dryness
• Itching

Other effects:

• Diarrhea
• Mouth sores
• Infection around nails
• Appetite and weight loss
• Bladder inflammation
• Nosebleeds
• Runny nose
• Fever
• Eye inflammation
• Low blood potassium 

Serious effects were uncommon.

Afatinib (Gilotrif) is a targeted drug approved by the United States Food and Drug Administration (FDA) after a 6-month review program because it was thought to offer treatment benefits. In addition, after erlotinib, it became the second drug approved this year with demonstrated benefit in prolonging progression-free survival in patients with metastatic non-small cell lung cancer carrying an EGFR mutation (19 deletion or 21 L858R).

Today's clinical findings has the potential to lead the way in targeted therapy by enabling more detailed examination of the molecular structure of cancer in the future.