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

LUX-Lung 5 Investigators

Research output: Contribution to journalArticle

76 Citations (Scopus)

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 languageEnglish
Pages (from-to)417-423
Number of pages7
JournalAnnals of Oncology
Volume27
Issue number3
DOIs
StatePublished - 1 Mar 2016

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Non-Small Cell Lung Carcinoma
Drug Therapy
Paclitaxel
Lung
Disease-Free Survival
gefitinib
Erlotinib Hydrochloride
BIBW 2992
Therapeutics
Health Status
Survival Rate
Quality of Life
Research Personnel
Safety

Keywords

  • Afatinib
  • NSCLC
  • Paclitaxel
  • Squamous cell

Cite this

@article{93f6ac745ba344ff99fd5c66256d0e71,
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).",
keywords = "Afatinib, NSCLC, Paclitaxel, Squamous cell",
author = "{LUX-Lung 5 Investigators} and Martin Schuler 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 S. Lu and J. Strausz and Y. Vinnyk and R. Wiewrodt and C. 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 Caicun Zhou 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 Kim, {Dong Wan}",
year = "2016",
month = "3",
day = "1",
doi = "10.1093/annonc/mdv597",
language = "English",
volume = "27",
pages = "417--423",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "3",

}

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

In: Annals of Oncology, Vol. 27, No. 3, 01.03.2016, p. 417-423.

Research output: Contribution to journalArticle

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 - LUX-Lung 5 Investigators

AU - Schuler, Martin

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, S.

AU - Strausz, J.

AU - Vinnyk, Y.

AU - Wiewrodt, R.

AU - Zhou, C.

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 - Zhou, Caicun

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 - Kim, Dong Wan

PY - 2016/3/1

Y1 - 2016/3/1

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).

KW - Afatinib

KW - NSCLC

KW - Paclitaxel

KW - Squamous cell

UR - http://www.scopus.com/inward/record.url?scp=84959893848&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdv597

DO - 10.1093/annonc/mdv597

M3 - Article

C2 - 26646759

AN - SCOPUS:84959893848

VL - 27

SP - 417

EP - 423

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 3

ER -