Dr Mekhail on Afatinib in Lung Cancers With Uncommon EGFR Mutations

Tarek M. Mekhail, MD, MSc, FRCSI, FRCSEd, medical director, Thoracic Oncology Program, AdventHealth Cancer Institute, associate professor, the University of Central Florida, discusses the prevalence of uncommon EGFR mutations in patients with lung cancer, research needs for these patients, and how the findings from the phase 3 LUX-Lung 3 (NCT00949650) and LUX-Lung 6 (NCT01121393) trials support the use of afatinib (Gilotrif) in this population.

Dr Mekhail on the Prevalence of Uncommon EGFR Mutations in Lung Cancer

In patients with lung cancer, uncommon EGFR mutations are becoming increasingly recognized through next-generation sequencing, Mekhail says. Around 6% of all patients with lung cancer will have a form of an uncommon EGFR mutation, Mekhail notes. However, limited data exist regarding drug activity in this population, as most clinical trials investigating first-, second-, and third-generation TKIs in patients with lung cancer have excluded those with uncommon EGFR mutations, Mekhail explains.

Dr Mekhail on LUX-Lung 3 and LUX-Lung 6 in Lung Cancers with Uncommon EGFR Mutations

The LUX-Lung 3 and Lux-Lung6 trials have provided information regarding the treatment of patients with lung cancer with uncommon EGFR mutations. LUX-Lung 3 investigated the efficacy and safety of afatinib vs pemetrexed (Alimta) and cisplatin in patients with EGFR-mutant advanced lung adenocarcinoma, including those with uncommon EGFR mutations. In this trial, treatment with afatinib led to a median progression-free survival (PFS) of 11.1 months vs 6.9 months in those who received pemetrexed plus cisplatin and an overall response rate (ORR) of 56% vs 23%, respectively. The median duration of disease control was 13.6 months and 8.1 months in the afatinib and chemotherapy arms, respectively. LUX-Lung 6 evaluated the safety and efficacy of afatinib vs cisplatin and gemcitabine in Asian patients with advanced non–small cell lung cancer harboring EGFR mutations, including uncommon EGFR mutations. In this trial, patients who received afatinib achieved a median PFS of 11.0 months vs 5.6 months in those who received the chemotherapy combination. The ORR was 66.9% and 23.0% in patients who received afatinib and chemotherapy, respectively. Additionally, the disease control rate (DCR) was 92.6% and 76.2% in the afatinib and chemotherapy arms, respectively.

Although the findings from these trials showed variable response rates, DCRs, and PFS, each trial had encouraging ORR, DCR, and PFS data, Mekhail emphasizes. The results from these trials support the use of afatinib in patients with lung cancer with uncommon EGFR mutations, Mekhail concludes.