In the LUX-Lung (LL) 3 and 6 trials, first-line afatinib significantly improved PFS versus chemotherapy in patients with EGFRm+ NSCLC and baseline BM (HR=0.50; P=0.0297).1 In LL7, similar PFS improvement with afatinib versus gefitinib was observed in patients with, and without, BM (HR, 0.74 and 0.76; Pint=0.93).2 The aims of this study were to assess: i) the impact of afatinib on CNS progression or metastatic spread in LL3, 6 and 7; ii) efficacy of afatinib in patients with BM in a ‘real-world’ setting.
Competing risk analysis of CNS/non-CNS progression or death was performed in patients who received afatinib in LL3, 6 and 7, based on the cumulative frequency of the event of interest versus the competing risk event. An Asian phase IIIb study assessed afatinib in a broad population of EGFR-TKI-naïve patients with EGFRm+ NSCLC (NCT01953913).3 PFS and time-to-symptomatic progression (TTSP) in patients with baseline BM were calculated by Kaplan-Meier methodology.
In patients with baseline BM receiving afatinib in LL3 and 6 (n=48; median follow-up: 10.3 months), risk of CNS progression was 40% lower than risk of extracranial progression; 31.3%/52.1% of patients had CNS/non-CNS progression, respectively. In patients without baseline BM receiving afatinib in LL3, 6 and 7 (n=485; median follow-up: 13.0 months), risk of de novo CNS/non-CNS progression was 6.4%/78.4%. Cumulative risk (CNS/non-CNS) was 1.3%/17.2% at 6 months and 2.6%/41.2% at 12 months. In the phase IIIb study, there was no difference in PFS (median 10.9 versus 12.4 months; P=0.18) or TTSP (median 14.8 versus 15.4 months; P=1.0) in patients with (n=92) or without (n=387) BM.
Competing risk analyses of LL3, 6 and 7 suggest that afatinib delays the onset/progression of BM. Real-world data are consistent with LL3, 6 and 7 and support the use of afatinib in patients with EGFRm+ NSCLC and baseline BM.