Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2018

Afatinib for patients with EGFR mutation-positive (EGFRm+) NSCLC: activity in patients with baseline brain metastases and impact on the rate of central nervous system (CNS) progression or spread (#336)

Kenneth O'Byrne 1 , James C-H Yang 2 , Yi-Long Wu 3 , Ver Hirsh 4 , Nobuyuki Yamamoto 5 , Sanjay Popat 6 , Akihiro Tamiya 7 , Angela Maerten 8 , Martin Schuler 9
  1. Princess Alexandra Hospital and Queensland University of Technology, New South Wales, Australia
  2. National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan
  3. Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China
  4. McGill University, Montreal, Canada
  5. Wakayama Medical University, Wakayama, Japan
  6. The Royal Marsden Hospital, London, United Kingdom
  7. Kinki-Chuo Chest Medical Center, Osaka, Japan
  8. Boehringer Ingelheim GmbH & Co. KG, Ingelheim am Rhein, Germany
  9. West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany

AIMS:

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.

 

METHODS:

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.

 

RESULTS:

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.

 

CONCLUSIONS:

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.

  1. Schuler, M. et al. J Thorac Oncol 2016;11:380‒90
  2. Park, K. et al. Lancet Oncol 2016;17:577‒89
  3. Wu YL, et al. J Thorac Oncol 2017;12(suppl 2):S2214