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

Martin Schuler, J. C H Yang, K. Park, J. H. Kim, J. Bennouna, Y. M. Chen, C. Chouaid, F. De Marinis, J. F. Feng, F. Grossi, D. W. Kim, X. Liu, S. Lu, J. Strausz, Y. Vinnyk, R. Wiewrodt, C. Zhou, B. Wang, V. K. Chand, D. PlanchardClaudia Bagnes, Claudio Marcelo Martin, Gonzalo Recondo, Juan Jose Zarba, Cesar Blajman, Martín Richardet, Sue Anne McLachlan, Phillip Parente, Craig Underhill, Catherine Crombie, Paul Mainwaring, Richard Greil, Yves Humblet, Frédérique Bustin, Luciano Carestia, Danny Galdermans, Marc Lambrechts, Laetitia Delval, Piet Vercauter, Caicun Zhou, Jin Wang, Cheng Huang, Xiaoyan Lin, Yilong Wu, Xiaoqing Liu, Ying Cheng, Shukui Qin, Jifeng Feng, Paolo Bidoli, Carlo Milandri, LUX-Lung 5 Investigators

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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/m2/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 (

Original languageEnglish
Article numbermdv597
Pages (from-to)417-423
Number of pages7
JournalAnnals of Oncology
Issue number3
Publication statusPublished - Mar 1 2016


  • Afatinib
  • Paclitaxel
  • Squamous cell

ASJC Scopus subject areas

  • Oncology
  • Hematology


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