Afatinib Delays Progression of Advanced Lung Cancer

Patients in a phase III study with common EGFR mutations derived most benefit.

Compared with standard chemotherapy, the novel targeted agent afatinib prolongs progression-free survival in patients with non–small cell lung cancer (NSCLC) driven by epidermal growth factor receptor (EGFR) mutations. That's according to researchers who led an international phase III trial of the drug and presented their results at the 2012 Annual Meeting of the American Society of Clinical Oncology, held in Chicago from June 1–5.

The researchers noted that afatinib (Boehringer Ingelheim) was particularly beneficial in patients with either deletion 19 or L858R, 2 common EGFR mutations, doubling the patients’ progression-free survival time. Together, these mutations account for about 90% of all EGFR mutations.

Previous studies have shown that afatinib irreversibly blocks the entire ErbB family of receptors, including EGFR, HER2, HER3, and HER4, unlike currently approved EGFR-targeted therapies, such as gefitinib (Iressa; AstraZeneca) and erlotinib (Tarceva; Roche and Astellas Pharma).

“By more broadly and effectively blocking the molecular pathways that facilitate the growth of these cancers, afatinib appears to be more potent than other therapies,” said James Chih-Hsin Yang, MD, PhD, a professor at the National Taiwan University and the principal investigator of the LUX-Lung 3 trial. Given its novel mode of action, the drug represents a new generation of tyrosine kinase inhibitors, he added.

The researchers randomly assigned 345 patients with advanced EGFR-mutation-positive NSCLC to receive afatinib or a combination of pemetrexed (Alimta; Lilly) and cisplatin, given intravenously. After a median follow-up of 8 months, they found that afatinib delayed disease progression by 11.1 months compared with 6.9 months for the chemotherapy regimen. Among the 308 patients with either deletion 19 or L858R, progression-free survival was even longer for those taking afatinib—13.6 months compared with 6.9 months. Yang estimated that data on overall survival will be available in about 2 years.

Side effects of afatinib were on par with those for other EGFR-targeted therapies. In addition, afatinib-treated patients took longer to develop worsening symptoms of lung cancer, such as coughing and shortness of breath. The researchers also reported better quality of life in these patients compared with those who received chemotherapy.

“This new treatment could not only help patients live a longer period of time without further cancer progression, but because it's given orally, it may also require fewer visits to the doctors’ office than standard chemotherapy,” commented Yang.

Two studies comparing afatinib with targeted treatment agents for lung cancer are recruiting patients: a phase IIB trial assessing afatinib against gefitinib as a first-line treatment in EGFR-mutation-positive NSCLC patients and a phase III trial evaluating afatinib versus erlotinib in second-line treatment of squamous cell carcinoma of the lung.