medwireNews: Afatinib significantly prolongs progression-free survival (PFS) in patients with metastatic lung adenocarcinoma and epidermal growth factor (EGFR) mutations, a phase III trial has found.
In the LUX-Lung 3 trial, patients given the oral ErbB family blocker as first-line therapy had a median PFS of 11.1 months, compared with just 6.9 months for their counterparts given standard doublet chemotherapy.
The results support afatinib as a standard treatment option for these patients, say James Chih-Hsin Yang (National Taiwan University, Taipei) and fellow investigators writing in the Journal of Clinical Oncology.
LUX-Lung 3 was a randomized open-label phase III study conducted at 133 centers in 25 countries in Asia, Europe, North America, South America, and Australia. A total of 345 patients were enrolled; all had EGFR mutations, predominantly exon 19 deletions (49%) and L858R point mutations (40%).
Patients were randomly assigned to receive oral afatinib 40 mg/day or cisplatin 75 mg/m2 plus pemetrexed 500 mg/m2 every 21 days for up to six cycles. The median duration of afatinib treatment was 11.0 months; 52% of patients required a dose reduction while 7% increased their dose to 50 mg/day.
After a median follow-up of 16.4 months, the primary endpoint – PFS – was significantly longer for patients given afatanib than those given chemotherapy, with a hazard ratio (HR) of 0.58.
The magnitude of treatment benefit was even greater among the subgroup of patients with common EGFR mutations, in whom median PFS was 13.6 months with afatanib versus 6.9 months with chemotherapy (HR=0.47). The afatanib benefit was consistent across all other subgroups examined.
Secondary analyses supported the superiority of afatanib, with the ErbB blocker being associated with significantly higher response rates than chemotherapy (56 vs 23% according to independent assessment) and significant delays in time to worsening of cough and dyspnea.
Around half of patients in each treatment arm experienced grade 3 or higher adverse events; however, toxicity was manageable and discontinuation due to drug-related adverse events was rare.
Noting that cisplatin plus pemetrexed “is widely considered the optimal chemotherapy doublet for patients with nonsquamous NSCLC,” Yang et al conclude that afatinib “could be considered a standard option” for patients with metastatic lung adenocarcinoma and EGFR mutations.
medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013