Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2016 Mar;27(3):417-23.
doi: 10.1093/annonc/mdv597. Epub 2015 Dec 8.

Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial

M Schuler  1 , J C-H Yang  2 , K Park  3 , J-H Kim  4 , J Bennouna  5 , Y-M Chen  6 , C Chouaid  7 , F De Marinis  8 , J-F Feng  9 , F Grossi  10 , D-W Kim  11 , X Liu  12 , S Lu  13 , J Strausz  14 , Y Vinnyk  15 , R Wiewrodt  16 , C Zhou  17 , B Wang  18 , V K Chand  19 , D Planchard  20 ; LUX-Lung 5 Investigators
Collaborators, Affiliations
Clinical Trial

Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial

M Schuler et al. Ann Oncol. 2016 Mar.

Abstract

Background: Afatinib has demonstrated clinical benefit in patients with non-small-cell lung cancer progressing after treatment with erlotinib/gefitinib. This phase III trial prospectively assessed whether continued irreversible ErbB-family blockade with afatinib plus paclitaxel has superior outcomes versus switching to chemotherapy alone in patients acquiring resistance to erlotinib/gefitinib and afatinib monotherapy.

Patients and methods: Patients with relapsed/refractory disease following ≥1 line of chemotherapy, and whose tumors had progressed following initial disease control (≥12 weeks) with erlotinib/gefitinib and thereafter afatinib (50 mg/day), were randomized 2:1 to receive afatinib plus paclitaxel (40 mg/day; 80 mg/m(2)/week) or investigator's choice of single-agent chemotherapy. The primary end point was progression-free survival (PFS). Other end points included objective response rate (ORR), overall survival (OS), safety and patient-reported outcomes.

Results: Two hundred and two patients with progressive disease following clinical benefit from afatinib were randomized to afatinib plus paclitaxel (n = 134) or single-agent chemotherapy (n = 68). PFS (median 5.6 versus 2.8 months, hazard ratio 0.60, P = 0.003) and ORR (32.1% versus 13.2%, P = 0.005) significantly improved with afatinib plus paclitaxel. There was no difference in OS. Global health status/quality of life was maintained with afatinib plus paclitaxel over the entire treatment period. The median treatment duration was 133 and 51 days with afatinib plus paclitaxel and single-agent chemotherapy, respectively; 48.5% of patients receiving afatinib plus paclitaxel and 30.0% of patients receiving single-agent chemotherapy experienced drug-related grade 3/4 adverse events. Treatment-related adverse events were consistent with those previously reported with each agent.

Conclusion: Afatinib plus paclitaxel improved PFS and ORR compared with single-agent chemotherapy in patients who acquired resistance to erlotinib/gefitinib and progressed on afatinib after initial benefit. LUX-Lung 5 is the first prospective trial to demonstrate the benefit of continued ErbB targeting post-progression, versus switching to single-agent chemotherapy.

Trial registration number: NCT01085136 (clinicaltrials.gov).

Keywords: NSCLC; afatinib; paclitaxel; squamous cell.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Kaplan–Meier curves for (A) PFS and (B) OS. CI, confidence interval; HR, hazard ratio; OS, overall survival; PFS, progression-free survival.
See this image and copyright information in PMC

Comment in

References

    1. Lee CK, Brown C, Gralla RJ et al. . Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis. J Natl Cancer Inst 2013; 105: 595–605. - PubMed
    1. Jackman D, Pao W, Riely GJ et al. . Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol 2010; 28: 357–360. - PMC - PubMed
    1. Chmielecki J, Foo J, Oxnard GR et al. . Optimization of dosing for EGFR-mutant non-small cell lung cancer with evolutionary cancer modeling. Sci Transl Med 2011; 3: 90ra59. - PMC - PubMed
    1. Chaft JE, Oxnard GR, Sima CS et al. . Disease flare after tyrosine kinase inhibitor discontinuation in patients with EGFR-mutant lung cancer and acquired resistance to erlotinib or gefitinib: implications for clinical trial design. Clin Cancer Res 2011; 17: 6298–6303. - PMC - PubMed
    1. Riely GJ, Kris MG, Zhao B et al. . Prospective assessment of discontinuation and reinitiation of erlotinib or gefitinib in patients with acquired resistance to erlotinib or gefitinib followed by the addition of everolimus. Clin Cancer Res 2007; 13: 5150–5155. - PubMed

Publication types

MeSH terms

Associated data