Osimertinib extends PFS vs SOC in first-line treatment of advanced NSCLC in FLAURA Asian subset
Osimertinib further extends progression-free survival (PFS) over standard-of-care (SOC) first-line therapy in Asian patients with advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), according to the Asian subset analysis of the phase III FLAURA* trial.
In this subset of 322 Asian participants, of whom 46 were Chinese, 120 Japanese, and 156 from other parts of Asia, patients with locally advanced or metastatic NSCLC (median age 64 years) with WHO performance status 0–1 and harbouring EGFR Ex19del or L858R were randomized to receive osimertinib (80 mg QD) or SOC treatment (erlotinib [150 mg QD] or gefitinib [250 mg QD]).
Patients on osimertinib demonstrated longer PFS compared with patients on SOC (median, 16.5 vs 11.0 months; hazard ratio [HR], 0.54, 95 percent confidence interval, 0.41–0.72; p<0.0001). [ESMO Asia 2017, abstract LBA6_PR]
While the overall response rate was comparable between patients in the osimertinib and SOC arms (80 percent vs 75 percent; odds ratio [OR], 1.33; p=0.2918), the duration of response among patients on osimertinib was double that of those on SOC (median, 18 vs 9 months; OR, 2.19; p=0.0002).
In terms of overall survival (OS), data is yet immature, though results point to “an interesting trend towards improved OS with osimertinib compared with SOC” (HR, 0.65; p=0.0609), said lead author Professor Byoung Chul Cho from the Yonsei Cancer Center in Seoul, Korea, who presented the findings of the Asian subset at ESMO Asia 2017.
Fewer patients on osimertinib than SOC experienced grade ≥3 adverse events (AEs; 40 percent vs 48 percent) or discontinued treatment due to any AEs (15 percent vs 21 percent).
Dermatitis acneiform, and AST and ALT increases occurred in a smaller proportion of patients on osimertinib compared with SOC (30 percent vs 53 percent, 12 percent vs 36 percent, and 7 percent vs 36 percent, respectively), while more patients on osimertinib experienced QT prolongation (15 percent vs 5 percent) and interstitial lung disease (6 percent vs 2 percent).
Osimertinib is currently approved and recommended for use in patients with T790M-positive NSCLC following treatment with an EGFR tyrosine kinase inhibitor (TKI). [Ann Oncol 2016;27(Suppl 5):v1-v27]
“As in the overall trial population, osimertinib provided a significant [PFS] benefit in Asian patients with EGFR-mutated NSCLC. Asian patients had similar toxicities with osimertinib as the overall FLAURA population,” said Cho.
“Data from this analysis support osimertinib as a new [SOC] for first-line therapy in Asian patients with EGFR-mutated advanced NSCLC,” he said.
“There is an ongoing debate as to whether Asian and non-Asian patients with EGFR mutations have distinct responses to EGFR-TKIs. This might be due to variations in clinical practice rather than biology,” said Professor James Yang from the National Taiwan University College of Medicine in Taipei, Taiwan, who called for further study to examine this issue as well as to identify the reasons behind treatment discontinuation.