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Ann Oncol. 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.

Collaborators (149)

Ou SH, Planchard D, Park K, Schuler M, Yang J, Chand V, Rohr K, Bagnes C, Martin CM, Recondo G, Zarba JJ, Blajman C, Richardet M, McLachlan SA, Parente P, Underhill C, Crombie C, Mainwaring P, Greil R, Humblet Y, Bustin F, Carestia L, Galdermans D, Lambrechts M, Delval L, Vercauter P, Zhou C, Wang J, Huang C, Lin X, Wu Y, Liu X, Cheng Y, Qin S, Feng J, Huang J, Zhang Y, Lu S, Zereu M, Garicochea B, Zadra CA, Riska H, Alanko T, Cadranel J, Chouaid C, Zalcman G, Sibilot DM, Perol M, Planchard D, Bennouna J, Fournel P, Gervais R, Rotarski M, Coudert B, Schuler M, Thomas M, Wehler T, Faehling M, Keilholz U, Laack E, von Pawel J, Huber R, Dickgreber N, Wiewrodt R, Mark Z, Tehenes S, Strausz J, Sarosi V, Prabhash K, Jain M, Venkatesan S, Sharma L, Dadhich H, Nagarkar RV, Onn A, Gottfried M, Stemmer S, Migliorino MR, Grossi F, Bidoli P, Bearz A, Gridelli C, Milandri C, Platania M, Ceresoli GL, Cruciani G, Gutierrez Delgado F, Gonzalez Perez JL, Luna GA, Padilla Baca O, Aerts J, Stigt J, Dingemans AM, Herder G, Gans S, Salas Sánchez JF, Alvarez Barreda RL, Rodriguez Pantigoso W, Mejia Palomino OL, Jaskiewicz P, Kazarnowicz A, Serwatowski P, Szczesna A, Jassem J, Lubennikov V, Karaseva N, Orlov S, Ragulin Y, Garrido P, González Larriba JL, Camps C, García Campelo R, Lianes P, Cobo M, Felip E, Kim DW, Kim SW, Park K, Kim JH, Han JY, Kim YC, Yang CH, Hsia TC, Chen YM, Tsai YH, Chang GC, Tsao TC, Su WC, Huang MS, Ho CL, Hsieh RK, Vinnyk Y, Popovych O, Ponomarova O, Bondarenko I, Polishchuk I, Shah R, Mitra S, Popat S, Spicer J, Toy E, Popat S, Talbot T, Brown E, Upadhyay S, Summers Y, Gurtler J, Meza L, Thropay J.

Author information

West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen German Cancer Research Center, German Cancer Consortium (DKTK), Heidelberg, Germany
Department of Medical Research, National Taiwan University and National Taiwan University Hospital, Taipei, Taiwan.
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul.
Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
Oncologie Médicale, Institut de Cancérologie de l'Ouest, Nantes, France.
Taipei Cancer Center, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Services de Pneumologie, CHI Créteil, Créteil, France.
1st Oncological Pulmonary Unit, San Camillo, High Specialization Hospital, Rome Thoracic Oncology Division, European Institute of Oncology, Milan, Italy.
Department of Medical Oncology, Jiangsu Province Cancer Hospital, Nanjing, China.
IRCCS AOU San Martino IST, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Lung Cancer, Seoul National University Hospital, Seoul, Republic of Korea.
Department of Pulmonary Oncology, Affiliated Hospital of Academy of Military Medical Science, Beijing.
Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Department of Pulmonology, Koranyi National Institute for Pulmonology, Budapest, Hungary.
Abdominal Department, Kharkiv Regional Clinical Oncology Center, Kharkiv, Ukraine.
Department of Medicine A, University Hospital, Münster, Germany.
Department of Oncology, Tongji University Medical School Cancer Institute, Shanghai, China.
Biostatistics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield.
Clinical Development Medical Affairs-Oncology, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, USA.
Department of Medical Oncology, Gustave Roussy, Villejuif, France.



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 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.


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.


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.


NCT01085136 (


NSCLC; afatinib; paclitaxel; squamous cell

[Indexed for MEDLINE]
Free PMC Article

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