After its initial approval in 2013 for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with exon 19 deletions or exon 21 L858R substitutions, afatinib was expanded to include patients with squamous histology following progression on a platinum-based chemotherapy in 2016.
Now in January of 2018, the FDA expanded the frontline indication for afatinib to include the treatment of patients with metastatic NSCLC whose tumors harbor the uncommon EGFR alterations: L861Q, G719X, and/or S768I.
This approval was based on findings from the phase II LUX-Lung 2 trial (LL2) and the randomized phase III trials known as LUX-Lung 3 (LL3) and LUX-Lung 6 (LL6). The objective response rate (ORR) across the 3 trials with afatinib was 66% (95% CI, 47%-81%). Among patients who responded, 52% had a duration of response (DoR) lasting longer than 12 months.
In February of this year, the FDA approved the PD-L1 inhibitor durvalumab for the treatment of patients with locally advanced, unresectable stage III NSCLC who have not progressed following chemoradiotherapy.
This approval was based on the phase III PACIFIC trial, in which durvalumab improved median progression-free survival (PFS) by 11.2 months compared with placebo (16.8 vs 5.6 months). The 12-month PFS rate was 55.9% versus 35.3%, and the 18-month PFS rate was 44.2% versus 27.0%, for durvalumab and placebo, respectively.
In April, osimertinib was approved as a first-line treatment option for patients with EGFR-mutated NSCLC based on the phase III FLAURA study.
In this trial osimertinib reduced the risk of progression or death by 54% compared with standard therapy with erlotinib or gefitinib. In the study, the median PFS was 18.9 months (95% CI, 15.2-21.4) with osimertinib compared with 10.2 months (95% CI, 9.6-11.1) for standard therapy.