92PD - First-line afatinib for advanced EGFRm+ NSCLC: Analysis of long-term responders (LTRs) in the LUX-Lung (LL) 3, 6 and 7 trials

Date 07 May 2017
Event ELCC 2017
Session Targeted therapies and immunotherapies
Topics Non-Small-Cell Lung Cancer, Locally Advanced
Cancer Immunology and Immunotherapy
Lung and other Thoracic Tumours
Presenter Martin Schuler
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors M. Schuler1, L. Paz-Ares2, L.V. Sequist3, Y. Wu4, S.L. Geater5, A. Märten6, J. Fan7, K. Park8, J.C. Yang9
  • 1West German Cancer Center, University Hospital Essen, University Duisburg-Essen, 45147 - Essen/DE
  • 2Hospital Universitario Doce de Octubre and CNIO, Madrid/ES
  • 3Massachusetts General Hospital and Harvard Medical School, Boston/US
  • 4Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou/CN
  • 5Department Of Internal Medicine, Prince of Songkla University, Songkla/TH
  • 6Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein/DE
  • 7Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield/US
  • 8Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul/KR
  • 9National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei/TW

Abstract

Background

In the Phase III LL3 and LL6 trials, first-line afatinib significantly improved PFS and ORR versus platinum-doublet chemotherapy in pts with EGFRm+ NSCLC. In the Phase IIb LL7 trial, afatinib significantly improved PFS, time to treatment failure, and ORR versus gefitinib in this setting. Here we present post-hoc analyses of afatinib LTRs (treated with afatinib ≥3 years) in LL3/6/7.

Methods

Treatment-naïve pts with stage IIIB/IV EGFRm+ NSCLC who were randomized to 40 mg/day afatinib in LL3/6/7 were included.

Results

24/229 (10%), 23/239 (10%) and 19/160 (12%) afatinib-treated pts in LL3, LL6 and LL7 were LTRs; 6, 9 and 14 LTRs were still on treatment at the time of analysis. In LL7, 4% of gefitinib-treated pts were LTRs. Baseline characteristics were generally consistent with the overall study populations, with the exception of greater proportions of women (LL3/6 only; 92/78% vs 64% in the overall populations) and Del19+ pts (63–79% vs 49–58% overall) among LTRs. The table shows treatment duration and outcomes. The median OS values for LL3/6 were >30 months longer than those reported in the overall populations. ORRs ranged from 70.8% in LL3 to 89.5% in LL7. Frequency and duration of subsequent therapy was similar to the overall population. Frequency of afatinib dose reduction due to TRAEs was broadly consistent with the overall populations; final afatinib doses of 20/30/40/50 mg were observed in 50/25/21/4% in LL3, 13/22/61/4% in LL6, and 32/21/47/0% in LL7.

Conclusions

In the LL3/6/7 studies, 10–12% of afatinib-treated pts were LTRs (treated ≥3 years). Among these pts, greater proportions of women (LL3/6 only) and Del19+ NSCLC were observed. In LTRs, afatinib conferred a long-term survival benefit of ∼5 years and was well tolerated. Long-term treatment was independent of tolerability-guided dose adjustment, or the presence of brain metastases at time of enrolment, and had no detrimental impact on subsequent treatment.rnTable: 92PDrn

rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn rnrn
CharacteristicLL3 (n = 24)LL6 (n = 23)LL7 (n = 19)
Median follow-up for OS, months64.657.042.1
Median duration of treatment, months (range)50 (41–73)56 (37–68)42 (37–50)
Median PFS (central review), months37.530.627.6
Median OS, months63.255.340.8
Overall response rate (CR+PR), n (%)17 (70.8)18 (78.3)17 (89.5)
CR, n (%)1 (4.2)3 (13.0)1 (5.3)
PR, n (%)16 (66.7)15 (65.2)16 (84.2)
SD, n (%)5 (20.8)2 (8.7)2 (10.5)
NN, n (%)2 (8.3)3 (13.0)
Median duration of response, months34.528.319.4
rn

CR, complete response; NN, not-PR/not-SD; PR, partial response; SD, stable disease

rn

Clinical trial identification

LUX-Lung 3: EudraCT No: 2008-005615-18 LUX-Lung 6: clinicaltrials.gov ref: NCT01121393 LUX-Lung 7: EudraCT No: 2011-001814-33

Legal entity responsible for the study

Boehringer Ingelheim

Funding

Boehringer Ingelheim

Disclosure

M. Schuler: Advisory boards: AstraZeneca, Boehringer Ingelheim, Celgene, Eli Lilly, Novartis; Corporate-sponsored research: Boehringer Ingelheim, Bristol-Myers Squibb, Novartis; Honoraria: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Novartis, Roche, MSD, Alexion; Patents: University Duisburg-Essen. L. Paz-Ares: Honoraria from Pfizer, Bristol-Myer Squibb, MSD, Novartis, Roche, Eli Lilly, Boehringer Ingelheim, Clovis Oncology, AstraZeneca, and Amgen. L.V. Sequist: Participated on advisory boards for Boehringer Ingelheim, AstraZeneca, Novartis, Clovis Oncology, Genentech, Merrimack, Ariad, and Bristol-Myers Squibb. S.L. Geater: Participated in advisory boards for Novartis and Boehringer Ingelheim, and has also received honoraria from Roche, AstraZeneca, Boehringer Ingelheim, and Novartis. A. Märten: Employee of Boehringer Ingelheim. J. Fan: Boehringer Ingelheim Pharmaceuticals Inc. employee. K. Park: Participated on advisory boards for Astellas, AstraZeneca, Boehringer Ingelheim, Clovis Oncology, Eli Lilly, Hanmi, MSD, Novartis, and Roche. J.C-H. Yang: Ad board and honoraria: BI, Lilly, Bayer, Roche/Genentech/Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis, Celgene, Merrimack, Yuhan Pharmaceuticals, BMS, Ono pharmaceutical Daiichi, Sankyo, and AZ. All other authors have declared no conflicts of interest.