A Phase IIIb open-label, single-arm study of afatinib in EGFR TKI-naïve patients with EGFRm+ NSCLC: An interim analysis.

Abstract

Background: In the Phase III LUX-Lung (LL) 3 and LL6 trials, first-line afatinibsignificantly improved PFS vs platinum-doublet chemotherapy in patients with EGFRm+ NSCLC (independent review; LL3: 11.1 vs 6.9 months, HR=0.58; p=0.001; LL6: 11.0 vs 5.6 months, HR=0.28; p<0.0001). In the Phase IIb LL7 trial, afatinib significantly improved PFS and TTF vs gefitinib in patients with EGFRm+ NSCLC harboring common EGFR mutations (PFS, independent review: 11.0 vs 10.9 months, HR=0.73; p=0.017; TTF: 13.7 vs 11.5 months, HR=0.73, p=0.0073). Here we report interim analysis results of a large Phase IIIb study of afatinib in a broad population of EGFR TKI-naïve patients with EGFRm+ NSCLC. Method: In this Phase IIIb trial with a similar setting to ‘real-world’ practice, EGFR TKI-naïve patients with locally advanced/ metastatic EGFRm+ NSCLC were recruited from centers in China, Hong Kong, India, Singapore and Taiwan and received afatinib 40mg/day until investigator-assessed progression or lack of tolerability. Primary endpoint: number of patients with serious adverse events (SAEs). Secondary endpoints included: number of patients with afatinib-related AEs; time to symptomatic progression (TTSP). Other assessments included PFS (investigator review). Result: At data cut-off (13 Feb 2017) 479 patients were treated with afatinib (median age: 59.0 years; female: 52.4%; common [(Del19 and/or L858R) with or without uncommon]/uncommon only EGFR mutations: 86.0%/14.0%; ECOG PS 0/1: 19.8%/78.1%; brain metastases: 19.2%; 0/1/≥2 lines of prior chemotherapy: 59.7%/30.1%/10.2%. 24.8% of patients required dose reductions to 30mg; 6.1% had further reductions to 20mg. Median (range) treatment time was 9.7 months (0.2–38.6). SAEs were reported in 115 (24.0%) patients and afatinibrelated SAEs in 29 (6.1%) patients. Grade ≥3 afatinib-related AEs occurred in 122 (25.5%) patients; diarrhea (n=50; 10.4%) and rash/acne (n=38; 7.9%) were the most common (≥5%). 18 (3.8%) patients discontinued treatment due to afatinib-related AEs. Median TTSP (15.3 months [95% CI: 13.4–17.5]) was 3 months longer than PFS (12.1 months [10.8–13.7]), suggesting afatinib may be continued beyond progression, and both were longer in patients with common (with/without uncommon) vs uncommon only EGFR mutations (PFS: 12.6 vs 9.1; TTSP: 15.8 vs 10.0 months). Conclusion: The safety data of afatinib from this interim analysis of a large-scale population of EGFR TKI-naïve EGFRm+ NSCLC patients are consistent with LL3/6/7 and confirm that most afatinib-related AEs are manageable and result in few treatment discontinuations. Afatinib also demonstrated encouraging efficacy in patients with common and uncommon EGFR mutations. Data from larger patient populations will be evaluated in further analyses of this trial.