Patient reported outcomes from LUX-Lung 3: first-line afatinib is superior to chemotherapy—would patients agree?

The LUX-Lung 3 trial was an important randomized phase 3 trial in patients with EGFR mutant advanced non-small cell lung cancer (NSCLC). Here, patients were randomized to either afatinib or cisplatinpemetrexed and the primary endpoint of progression-free survival (PFS) was easily met (HR=0.58, P=0.001). This was the first large-scale trial of this type using a modern chemotherapy comparator, including Asian and non- Asian patients, central radiology review, and utilizing comprehensive patient-reported outcomes. Whilst efficacy for afatinib was markedly superior to chemotherapy, do the patient-reported outcomes reflect this superiority? The symptom control and quality of life (QoL) data from this trial has now been published. Analysis of these demonstrate clear superiority of afatinib over chemotherapy for delay in cough deterioration, and dyspnoea. Notably, given the toxicity profile of afatinib, these improvements translated into significant improvements in global health status, physical, role, and cognitive functioning. The clinical benefits for afatinib over cisplatinpemetrexed chemotherapy for EGFR mutation-positive advanced non-small cell lung patients seem overwhelming, and are clinically meaningful. These results are also consistent with QoL data from other trials of gefitinib/ erlotinib, but much more robust, given the larger patient numbers. Would patients agree that afatinib is superior to chemotherapy? On the basis of data presented, the answer is probably “Yes”. However, the key unanswered question remaining is “Which is the best EGFR-tyrosine kinase inhibitor (TKI) to use up front?” and we will have to wait until ongoing trial data can help answer this.