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; LUX-Lung 5 Investigators; J. C.H. Yang; K. Park; J. H. Kim; J. Bennouna; Y. M. Chen; C. Chouaid; F. De Marinis; J. F. Feng; Francesco Grossi; D. W. Kim; X. Liu; Shun Lu; J. Strausz; Y. Vinnyk; R. Wiewrodt; Caicun Zhou; B. Wang; V. K. Chand; D. Planchard; Joachim Aerts; Anne Marie Dingemans

doi:10.1093/annonc/mdv597

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^*
, LUX-Lung 5 Investigators
, J. C.H. Yang
, K. Park
, J. H. Kim
, J. Bennouna
, Y. M. Chen
, C. Chouaid
, F. De Marinis
, J. F. Feng
, Francesco Grossi
, D. W. Kim
, X. Liu
, Shun Lu
, J. Strausz
, Y. Vinnyk
, R. Wiewrodt
, Caicun Zhou
, B. Wang
, V. K. Chand

D. Planchard, Joachim Aerts, Anne Marie Dingemans

^*Corresponding author for this work

Pulmonary Medicine

University Hospital Essen
German Cancer Research Center
Sungkyunkwan University
Oncologie
CHI de Créteil
High Specialization Hospital
IRCCS Istituto Europeo di Oncologia - Milano
San Martino Hospital Genoa
Seoul National University
Shanghai Jiao Tong University
National Koranyi Institute of TB and Pulmonology
Kharkiv Regional Clinical Oncology Center
University Hospital Münster
Tongji University
Boehringer Ingelheim GmbH
Institut Gustave Roussy
National Taiwan University
National Taiwan University Hospital
Yonsei University
Taipei Cancer Center
Taipei Medical University
Jiangsu Province Cancer Hospital
Affiliated Hospital of Academy of Military Medical Science
Boehringer Ingelheim Pharmaceuticals Inc

Research output: Contribution to journal › Article › Academic › peer-review

129 Citations (Scopus)

57 Downloads (Pure)

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/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 (clinicaltrials.gov).

Original language	English
Pages (from-to)	417-423
Number of pages	7
Journal	Annals of Oncology
Volume	27
Issue number	3
DOIs	https://doi.org/10.1093/annonc/mdv597
Publication status	Published - Mar 2016

Bibliographical note

Publisher Copyright:
© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

funding:
This work was supported by Boehringer Ingelheim. Medical
writing assistance, supported financially by Boehringer Ingelheim,
was provided by Lynn Pritchard of GeoMed, an Ashfield
company, part of UDG Healthcare plc, during the preparation of
this article. There is no applicable grant number

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1093/annonc/mdv597Licence: CC BY-NC

Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinibgefitinib and afatinibFinal published version, 216 KBLicence: CC BY-NC

Cite this

Schuler, M., LUX-Lung 5 Investigators, Yang, J. C. H., Park, K., Kim, J. H., Bennouna, J., Chen, Y. M., Chouaid, C., De Marinis, F., Feng, J. F., Grossi, F., Kim, D. W., Liu, X., Lu, S., Strausz, J., Vinnyk, Y., Wiewrodt, R., Zhou, C., Wang, B., ... Dingemans, A. M. (2016). Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: Phase III randomized LUX-Lung 5 trial. Annals of Oncology, 27(3), 417-423. https://doi.org/10.1093/annonc/mdv597

@article{25e7afcde8274726b6fb943617226866,

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

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/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 (clinicaltrials.gov).",

author = "Martin Schuler and \{LUX-Lung 5 Investigators\} and Yang, \{J. C.H.\} and K. Park and Kim, \{J. H.\} and J. Bennouna and Chen, \{Y. M.\} and C. Chouaid and \{De Marinis\}, F. and Feng, \{J. F.\} and Francesco Grossi and Kim, \{D. W.\} and X. Liu and Shun Lu and J. Strausz and Y. Vinnyk and R. Wiewrodt and Caicun Zhou and B. Wang and Chand, \{V. K.\} and D. Planchard and Claudia Bagnes and Martin, \{Claudio Marcelo\} and Gonzalo Recondo and Zarba, \{Juan Jose\} and Cesar Blajman and Mart{\'i}n Richardet and McLachlan, \{Sue Anne\} and Phillip Parente and Craig Underhill and Catherine Crombie and Paul Mainwaring and Richard Greil and Yves Humblet and Fr{\'e}d{\'e}rique Bustin and Luciano Carestia and Danny Galdermans and Marc Lambrechts and Laetitia Delval and Piet Vercauter and Jin Wang and Cheng Huang and Xiaoyan Lin and Yilong Wu and Xiaoqing Liu and Ying Cheng and Shukui Qin and Jifeng Feng and Jianjin Huang and Joachim Aerts and Dingemans, \{Anne Marie\}",

note = "Publisher Copyright: {\textcopyright} The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. funding: This work was supported by Boehringer Ingelheim. Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Lynn Pritchard of GeoMed, an Ashfield company, part of UDG Healthcare plc, during the preparation of this article. There is no applicable grant number",

year = "2016",

month = mar,

doi = "10.1093/annonc/mdv597",

language = "English",

volume = "27",

pages = "417--423",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Elsevier Ltd.",

number = "3",

}

Schuler, M, LUX-Lung 5 Investigators, Yang, JCH, Park, K, Kim, JH, Bennouna, J, Chen, YM, Chouaid, C, De Marinis, F, Feng, JF, Grossi, F, Kim, DW, Liu, X, Lu, S, Strausz, J, Vinnyk, Y, Wiewrodt, R, Zhou, C, Wang, B, Chand, VK, Planchard, D, Aerts, J & Dingemans, AM 2016, 'Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: Phase III randomized LUX-Lung 5 trial', Annals of Oncology, vol. 27, no. 3, pp. 417-423. https://doi.org/10.1093/annonc/mdv597

Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: Phase III randomized LUX-Lung 5 trial. / Schuler, Martin; LUX-Lung 5 Investigators; Yang, J. C.H. et al.
In: Annals of Oncology, Vol. 27, No. 3, 03.2016, p. 417-423.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib

T2 - Phase III randomized LUX-Lung 5 trial

AU - Schuler, Martin

AU - LUX-Lung 5 Investigators

AU - Yang, J. C.H.

AU - Park, K.

AU - Kim, J. H.

AU - Bennouna, J.

AU - Chen, Y. M.

AU - Chouaid, C.

AU - De Marinis, F.

AU - Feng, J. F.

AU - Grossi, Francesco

AU - Kim, D. W.

AU - Liu, X.

AU - Lu, Shun

AU - Strausz, J.

AU - Vinnyk, Y.

AU - Wiewrodt, R.

AU - Zhou, Caicun

AU - Wang, B.

AU - Chand, V. K.

AU - Planchard, D.

AU - Bagnes, Claudia

AU - Martin, Claudio Marcelo

AU - Recondo, Gonzalo

AU - Zarba, Juan Jose

AU - Blajman, Cesar

AU - Richardet, Martín

AU - McLachlan, Sue Anne

AU - Parente, Phillip

AU - Underhill, Craig

AU - Crombie, Catherine

AU - Mainwaring, Paul

AU - Greil, Richard

AU - Humblet, Yves

AU - Bustin, Frédérique

AU - Carestia, Luciano

AU - Galdermans, Danny

AU - Lambrechts, Marc

AU - Delval, Laetitia

AU - Vercauter, Piet

AU - Wang, Jin

AU - Huang, Cheng

AU - Lin, Xiaoyan

AU - Wu, Yilong

AU - Liu, Xiaoqing

AU - Cheng, Ying

AU - Qin, Shukui

AU - Feng, Jifeng

AU - Huang, Jianjin

AU - Aerts, Joachim

AU - Dingemans, Anne Marie

N1 - Publisher Copyright: © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. funding: This work was supported by Boehringer Ingelheim. Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Lynn Pritchard of GeoMed, an Ashfield company, part of UDG Healthcare plc, during the preparation of this article. There is no applicable grant number

PY - 2016/3

Y1 - 2016/3

N2 - 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 (clinicaltrials.gov).

AB - 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 (clinicaltrials.gov).

UR - https://www.scopus.com/pages/publications/84959893848

U2 - 10.1093/annonc/mdv597

DO - 10.1093/annonc/mdv597

M3 - Article

C2 - 26646759

AN - SCOPUS:84959893848

SN - 0923-7534

VL - 27

SP - 417

EP - 423

JO - Annals of Oncology

JF - Annals of Oncology

IS - 3

ER -

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

Abstract

Bibliographical note

UN SDGs

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