Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: Phase III randomized LUX-Lung 5 trial
Journal
Annals of Oncology
Journal Volume
27
Journal Issue
3
Pages
417-423
Date Issued
2016
Author(s)
Schuler M
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
Chand V.K
Planchard D
Bagnes C
Martin C.M
Recondo G
Zarba J.J
Blajman C
Richardet M
McLachlan S.-A
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 C.A
Riska H
Alanko T
Cadranel J
Chouaid C
Zalcman G
Sibilot D.M
Perol M
Planchard D
Bennouna J
Fournel P
Gervais R
Rotarski M
Coudert B
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 R.V
Onn A
Gottfried M
Stemmer S
Migliorino M.R
Bidoli P
Bearz A
Gridelli C
Milandri C
Platania M
Ceresoli G.L
Cruciani G
Delgado F.G
Perez J.L.G
Luna G.A
Baca O.P
Aerts J
Stigt J
Dingemans A.-M
Herder G
Gans S
Sánchez J.F.S
Barreda R.L.A
Pantigoso W.R
Palomino O.L.M
Jaskiewicz P
Kazarnowicz A
Serwatowski P
Szczesna A
Jassem J
Lubennikov V
Karaseva N
Orlov S
Ragulin Y
Garrido P
Larriba J.L.G
Camps C
Campelo R.G
Lianes P
Cobo M
Felip E
Kim D.-W
Kim S.-W
Park K
Kim J.-H
Han J.-Y
Kim Y.-C
Yang C.-H
Hsia T.-C
Chen Y.-M
Tsai Y.-H
Chang G.-C
Tsao T.C.-Y
Su W.-C
Huang M.-S
Ho C.-L
Hsieh R.-K
Vinnyk Y
Popovych O
Ponomarova O
Bondarenko I
Polishchuk I
Shah R
Mitra S
Popat S
Spicer J
Toy E
Talbot T
Brown E
Upadhyay S
Summers Y
Gurtler J
Meza L
Thropay J
LUX-Lung 5 Investigators
Abstract
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 (clinicaltrials.gov).
SDGs
Publisher
Oxford University Press
Type
journal article