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

Eight large-scale clinical trials have now demonstrated the superiority of first-generation EGFR-tyrosine kinase inhibitor (TKI) (gefitinib/erlotinib) over platinum doublet chemotherapy (1-8). Afatinib is a second-generation EGFR-TKI designed to irreversibly inhibit EGFR kinase, including the T790M gatekeeper mutation that accounts for acquired resistance to gefitinib/erlotinib therapy in around 50% of cases (9). The LUX-Lung 3 trial was the first randomized trial of a second generation EGFR-TKI compared to a modern chemotherapy doublet—cisplatin-pemetrexed—in patients with treatment na？ve EGFR mutant advanced non-small cell lung cancer (NSCLC) (6). The trial recruited both Asian and non-Asian patients, as was the largest trial in this indication thus far, utilizing independent radiology review. Afatinib demonstrated marked clinical efficacy over cisplatin-pemetrexed [progression-free survival (PFS) median 11.1 vs. 6.9 months, HR=0.58, 0.43-0.78, P=0.001; improving to PFS median 13.6 vs. 6.9 months, HR=0.47, 0.34-0.65, P=0.001 when restricted to the common mutations L858R and exon 19 deletions]. Toxicities for afatinib were as observed in previous trials, with diarrhoea, rash, and paronychia the most prevalent (≥ grade 3 adverse events 14.4%, 16.2%, 11.4%, respectively). Of course, these were the worst grade of toxicity reported per patient, and duration of afatinib therapy was markedly longer than that of cisplatin-pemetrexed