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, Jaafar Bennouna, Y. M. Chen, C. Chouaid, Filippo De Marinis, J. F. Feng, Francesco Grossi, D. W. Kim, X. Liu, S. Lu, J. Strausz, Y. Vinnyk, R. Wiewrodt, C. Zhou, B. Wang, Vikram K. Chand, D. PlanchardClaudia Bagnes, Claudio Marcelo Martin, Gonzalo Recondo, Juan Jose Zarba, Cesar R. Blajman, Martín Richardet, Sue Anne McLachlan, Phillip Parente, Craig Underhill, Catherine Crombie, P. Mainwaring, Richard Greil, Y. Humblet, Frederique 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, Jianjin Huang, Yiping Zhang, Shun Lu, Manuela Zereu, Bernardo Garicochea, Cyntia Albuquerque Zadra, Henrik Riska, Tuomo Alanko, Jacques Cadranel, Christos Chouaid, Gérard Zalcman, Denis Moro Sibilot, Maurice Perol, David Planchard, Jaafar Bennouna, Pierre Fournel, Radj Gervais, Maciej Rotarski, Bruno Coudert, Michael Thomas, Thomas Wehler, Martin Faehling, Ulrich Keilholz, Eckart Laack, J. von Pawel, Rudolf Huber, Nicolas Dickgreber, Rainer Wiewrodt, Z. Mark, S. Tehenes, Janos Strausz, Veronika Sarosi, Kumar Prabhash, Minish Jain, Srinivasan Venkatesan, Lalit Sharma, Hemant Dadhich, Rajnish Vasant Nagarkar, Amir Onn, Maya Gottfried, Solomon Stemmer, M. R. Migliorino, Francesco Grossi, Alessandra Bearz, Alessandra Bearz, Cesare Gridelli, Marco Platania, Marco Platania, Giovanni Ceresoli, Giorgio Cruciani, Francisco Gutierrez Delgado, José Luis Gonzalez Perez, Gabriela Alvarado Luna, Othon Padilla Baca, Joachim Aerts, Jos Stigt, Anne Marie C Dingemans, Gerarda Herder, Steven Gans, Jorge Fernando Salas Sánchez, Renzo Luzgardo Alvarez Barreda, Wilbert Rodriguez Pantigoso, Osbert Luis Mejia Palomino, Piotr Jaskiewicz, Andrzej Kazarnowicz, P. Serwatowski, Aleksandra Szczesna, J. Jassem, Vladimir Lubennikov, Nina Karaseva, S. Orlov, Yuri Ragulin, Pilar Garrido, José Luis González Larriba, Carlos Camps, Rosario García Campelo, Pilar Lianes, Manuel Cobo, Enriqueta Felip, Dong Wan Kim, Sang We Kim, Keunchil Park, Joo Hang Kim, Ji Youn Han, Young Chul Kim, Chih Hsin Yang, Te Chun Hsia, Yuh Min Chen, Ying Huang Tsai, Gee Chen Chang, Thomas Chang Yao Tsao, Wu Chou Su, Ming Shyan Huang, Ching Liang Ho, Ruey Kuen Hsieh, Yuriy Vinnyk, Oleksandr Popovych, Olga Ponomarova, Igor Bondarenko, Iryna Polishchuk, Riyaz Shah, Sanka Mitra, Sanjaykumar Popat, James Spicer, Elizabeth Toy, Toby Talbot, Emma Brown, Sunil Upadhyay, Y. Summers, Jayne Gurtler, Luis Meza, John Thropay

Research output: Contribution to journalArticle

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
Article numbermdv597
Pages (from-to)417-423
Number of pages7
JournalAnnals of Oncology
Volume27
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

Fingerprint

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

Keywords

  • Afatinib
  • NSCLC
  • Paclitaxel
  • Squamous cell

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

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; Yang, J. C H; Park, K.; Kim, J. H.; Bennouna, Jaafar; Chen, Y. M.; Chouaid, C.; De Marinis, Filippo; Feng, J. F.; Grossi, Francesco; Kim, D. W.; Liu, X.; Lu, S.; Strausz, J.; Vinnyk, Y.; Wiewrodt, R.; Zhou, C.; Wang, B.; Chand, Vikram K.; Planchard, D.; Bagnes, Claudia; Martin, Claudio Marcelo; Recondo, Gonzalo; Zarba, Juan Jose; Blajman, Cesar R.; Richardet, Martín; McLachlan, Sue Anne; Parente, Phillip; Underhill, Craig; Crombie, Catherine; Mainwaring, P.; Greil, Richard; Humblet, Y.; Bustin, Frederique; Carestia, Luciano; Galdermans, Danny; Lambrechts, Marc; Delval, Laetitia; Vercauter, Piet; Zhou, Caicun; Wang, Jin; Huang, Cheng; Lin, Xiaoyan; Wu, Yilong; Liu, Xiaoqing; Cheng, Ying; Qin, Shukui; Feng, Jifeng; Huang, Jianjin; Zhang, Yiping; Lu, Shun; Zereu, Manuela; Garicochea, Bernardo; Zadra, Cyntia Albuquerque; Riska, Henrik; Alanko, Tuomo; Cadranel, Jacques; Chouaid, Christos; Zalcman, Gérard; Sibilot, Denis Moro; Perol, Maurice; Planchard, David; Bennouna, Jaafar; Fournel, Pierre; Gervais, Radj; Rotarski, Maciej; Coudert, Bruno; Thomas, Michael; Wehler, Thomas; Faehling, Martin; Keilholz, Ulrich; Laack, Eckart; von Pawel, J.; Huber, Rudolf; Dickgreber, Nicolas; Wiewrodt, Rainer; Mark, Z.; Tehenes, S.; Strausz, Janos; Sarosi, Veronika; Prabhash, Kumar; Jain, Minish; Venkatesan, Srinivasan; Sharma, Lalit; Dadhich, Hemant; Nagarkar, Rajnish Vasant; Onn, Amir; Gottfried, Maya; Stemmer, Solomon; Migliorino, M. R.; Grossi, Francesco; Bearz, Alessandra; Bearz, Alessandra; Gridelli, Cesare; Platania, Marco; Platania, Marco; Ceresoli, Giovanni; Cruciani, Giorgio; Delgado, Francisco Gutierrez; Perez, José Luis Gonzalez; Luna, Gabriela Alvarado; Baca, Othon Padilla; Aerts, Joachim; Stigt, Jos; Dingemans, Anne Marie C; Herder, Gerarda; Gans, Steven; Sánchez, Jorge Fernando Salas; Barreda, Renzo Luzgardo Alvarez; Pantigoso, Wilbert Rodriguez; Palomino, Osbert Luis Mejia; Jaskiewicz, Piotr; Kazarnowicz, Andrzej; Serwatowski, P.; Szczesna, Aleksandra; Jassem, J.; Lubennikov, Vladimir; Karaseva, Nina; Orlov, S.; Ragulin, Yuri; Garrido, Pilar; Larriba, José Luis González; Camps, Carlos; Campelo, Rosario García; Lianes, Pilar; Cobo, Manuel; Felip, Enriqueta; Kim, Dong Wan; Kim, Sang We; Park, Keunchil; Kim, Joo Hang; Han, Ji Youn; Kim, Young Chul; Yang, Chih Hsin; Hsia, Te Chun; Chen, Yuh Min; Tsai, Ying Huang; Chang, Gee Chen; Tsao, Thomas Chang Yao; Su, Wu Chou; Huang, Ming Shyan; Ho, Ching Liang; Hsieh, Ruey Kuen; Vinnyk, Yuriy; Popovych, Oleksandr; Ponomarova, Olga; Bondarenko, Igor; Polishchuk, Iryna; Shah, Riyaz; Mitra, Sanka; Popat, Sanjaykumar; Spicer, James; Toy, Elizabeth; Talbot, Toby; Brown, Emma; Upadhyay, Sunil; Summers, Y.; Gurtler, Jayne; Meza, Luis; Thropay, John.

In: Annals of Oncology, Vol. 27, No. 3, mdv597, 01.03.2016, p. 417-423.

Research output: Contribution to journalArticle

Schuler, M, 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, Bagnes, C, Martin, CM, Recondo, G, Zarba, JJ, Blajman, CR, 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, 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, Bearz, A, Bearz, A, Gridelli, C, Platania, M, Platania, M, Ceresoli, G, Cruciani, G, Delgado, FG, Perez, JLG, Luna, GA, Baca, OP, Aerts, J, Stigt, J, Dingemans, AMC, Herder, G, Gans, S, Sánchez, JFS, Barreda, RLA, Pantigoso, WR, Palomino, OLM, Jaskiewicz, P, Kazarnowicz, A, Serwatowski, P, Szczesna, A, Jassem, J, Lubennikov, V, Karaseva, N, Orlov, S, Ragulin, Y, Garrido, P, Larriba, JLG, Camps, C, Campelo, RG, 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, TCY, 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, Talbot, T, Brown, E, Upadhyay, S, Summers, Y, Gurtler, J, Meza, L & Thropay, J 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, mdv597, pp. 417-423. https://doi.org/10.1093/annonc/mdv597
Schuler, Martin ; Yang, J. C H ; Park, K. ; Kim, J. H. ; Bennouna, Jaafar ; Chen, Y. M. ; Chouaid, C. ; De Marinis, Filippo ; Feng, J. F. ; Grossi, Francesco ; Kim, D. W. ; Liu, X. ; Lu, S. ; Strausz, J. ; Vinnyk, Y. ; Wiewrodt, R. ; Zhou, C. ; Wang, B. ; Chand, Vikram K. ; Planchard, D. ; Bagnes, Claudia ; Martin, Claudio Marcelo ; Recondo, Gonzalo ; Zarba, Juan Jose ; Blajman, Cesar R. ; Richardet, Martín ; McLachlan, Sue Anne ; Parente, Phillip ; Underhill, Craig ; Crombie, Catherine ; Mainwaring, P. ; Greil, Richard ; Humblet, Y. ; Bustin, Frederique ; Carestia, Luciano ; Galdermans, Danny ; Lambrechts, Marc ; Delval, Laetitia ; Vercauter, Piet ; Zhou, Caicun ; Wang, Jin ; Huang, Cheng ; Lin, Xiaoyan ; Wu, Yilong ; Liu, Xiaoqing ; Cheng, Ying ; Qin, Shukui ; Feng, Jifeng ; Huang, Jianjin ; Zhang, Yiping ; Lu, Shun ; Zereu, Manuela ; Garicochea, Bernardo ; Zadra, Cyntia Albuquerque ; Riska, Henrik ; Alanko, Tuomo ; Cadranel, Jacques ; Chouaid, Christos ; Zalcman, Gérard ; Sibilot, Denis Moro ; Perol, Maurice ; Planchard, David ; Bennouna, Jaafar ; Fournel, Pierre ; Gervais, Radj ; Rotarski, Maciej ; Coudert, Bruno ; Thomas, Michael ; Wehler, Thomas ; Faehling, Martin ; Keilholz, Ulrich ; Laack, Eckart ; von Pawel, J. ; Huber, Rudolf ; Dickgreber, Nicolas ; Wiewrodt, Rainer ; Mark, Z. ; Tehenes, S. ; Strausz, Janos ; Sarosi, Veronika ; Prabhash, Kumar ; Jain, Minish ; Venkatesan, Srinivasan ; Sharma, Lalit ; Dadhich, Hemant ; Nagarkar, Rajnish Vasant ; Onn, Amir ; Gottfried, Maya ; Stemmer, Solomon ; Migliorino, M. R. ; Grossi, Francesco ; Bearz, Alessandra ; Bearz, Alessandra ; Gridelli, Cesare ; Platania, Marco ; Platania, Marco ; Ceresoli, Giovanni ; Cruciani, Giorgio ; Delgado, Francisco Gutierrez ; Perez, José Luis Gonzalez ; Luna, Gabriela Alvarado ; Baca, Othon Padilla ; Aerts, Joachim ; Stigt, Jos ; Dingemans, Anne Marie C ; Herder, Gerarda ; Gans, Steven ; Sánchez, Jorge Fernando Salas ; Barreda, Renzo Luzgardo Alvarez ; Pantigoso, Wilbert Rodriguez ; Palomino, Osbert Luis Mejia ; Jaskiewicz, Piotr ; Kazarnowicz, Andrzej ; Serwatowski, P. ; Szczesna, Aleksandra ; Jassem, J. ; Lubennikov, Vladimir ; Karaseva, Nina ; Orlov, S. ; Ragulin, Yuri ; Garrido, Pilar ; Larriba, José Luis González ; Camps, Carlos ; Campelo, Rosario García ; Lianes, Pilar ; Cobo, Manuel ; Felip, Enriqueta ; Kim, Dong Wan ; Kim, Sang We ; Park, Keunchil ; Kim, Joo Hang ; Han, Ji Youn ; Kim, Young Chul ; Yang, Chih Hsin ; Hsia, Te Chun ; Chen, Yuh Min ; Tsai, Ying Huang ; Chang, Gee Chen ; Tsao, Thomas Chang Yao ; Su, Wu Chou ; Huang, Ming Shyan ; Ho, Ching Liang ; Hsieh, Ruey Kuen ; Vinnyk, Yuriy ; Popovych, Oleksandr ; Ponomarova, Olga ; Bondarenko, Igor ; Polishchuk, Iryna ; Shah, Riyaz ; Mitra, Sanka ; Popat, Sanjaykumar ; Spicer, James ; Toy, Elizabeth ; Talbot, Toby ; Brown, Emma ; Upadhyay, Sunil ; Summers, Y. ; Gurtler, Jayne ; Meza, Luis ; Thropay, John. / Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib : Phase III randomized LUX-Lung 5 trial. In: Annals of Oncology. 2016 ; Vol. 27, No. 3. pp. 417-423.
@article{27721c5154c647a7b5e7e40b879f5b3f,
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 = "Martin Schuler and Yang, {J. C H} and K. Park and Kim, {J. H.} and Jaafar Bennouna and Chen, {Y. M.} and C. Chouaid and {De Marinis}, Filippo 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, {Vikram K.} and D. Planchard and Claudia Bagnes and Martin, {Claudio Marcelo} and Gonzalo Recondo and Zarba, {Juan Jose} and Blajman, {Cesar R.} and Mart{\'i}n Richardet and McLachlan, {Sue Anne} and Phillip Parente and Craig Underhill and Catherine Crombie and P. Mainwaring and Richard Greil and Y. Humblet and Frederique 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 Yiping Zhang and Shun Lu and Manuela Zereu and Bernardo Garicochea and Zadra, {Cyntia Albuquerque} and Henrik Riska and Tuomo Alanko and Jacques Cadranel and Christos Chouaid and G{\'e}rard Zalcman and Sibilot, {Denis Moro} and Maurice Perol and David Planchard and Jaafar Bennouna and Pierre Fournel and Radj Gervais and Maciej Rotarski and Bruno Coudert and Michael Thomas and Thomas Wehler and Martin Faehling and Ulrich Keilholz and Eckart Laack and {von Pawel}, J. and Rudolf Huber and Nicolas Dickgreber and Rainer Wiewrodt and Z. Mark and S. Tehenes and Janos Strausz and Veronika Sarosi and Kumar Prabhash and Minish Jain and Srinivasan Venkatesan and Lalit Sharma and Hemant Dadhich and Nagarkar, {Rajnish Vasant} and Amir Onn and Maya Gottfried and Solomon Stemmer and Migliorino, {M. R.} and Francesco Grossi and Alessandra Bearz and Alessandra Bearz and Cesare Gridelli and Marco Platania and Marco Platania and Giovanni Ceresoli and Giorgio Cruciani and Delgado, {Francisco Gutierrez} and Perez, {Jos{\'e} Luis Gonzalez} and Luna, {Gabriela Alvarado} and Baca, {Othon Padilla} and Joachim Aerts and Jos Stigt and Dingemans, {Anne Marie C} and Gerarda Herder and Steven Gans and S{\'a}nchez, {Jorge Fernando Salas} and Barreda, {Renzo Luzgardo Alvarez} and Pantigoso, {Wilbert Rodriguez} and Palomino, {Osbert Luis Mejia} and Piotr Jaskiewicz and Andrzej Kazarnowicz and P. Serwatowski and Aleksandra Szczesna and J. Jassem and Vladimir Lubennikov and Nina Karaseva and S. Orlov and Yuri Ragulin and Pilar Garrido and Larriba, {Jos{\'e} Luis Gonz{\'a}lez} and Carlos Camps and Campelo, {Rosario Garc{\'i}a} and Pilar Lianes and Manuel Cobo and Enriqueta Felip and Kim, {Dong Wan} and Kim, {Sang We} and Keunchil Park and Kim, {Joo Hang} and Han, {Ji Youn} and Kim, {Young Chul} and Yang, {Chih Hsin} and Hsia, {Te Chun} and Chen, {Yuh Min} and Tsai, {Ying Huang} and Chang, {Gee Chen} and Tsao, {Thomas Chang Yao} and Su, {Wu Chou} and Huang, {Ming Shyan} and Ho, {Ching Liang} and Hsieh, {Ruey Kuen} and Yuriy Vinnyk and Oleksandr Popovych and Olga Ponomarova and Igor Bondarenko and Iryna Polishchuk and Riyaz Shah and Sanka Mitra and Sanjaykumar Popat and James Spicer and Elizabeth Toy and Toby Talbot and Emma Brown and Sunil Upadhyay and Y. Summers and Jayne Gurtler and Luis Meza and John Thropay",
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 = "NLM (Medline)",
number = "3",

}

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 - Yang, J. C H

AU - Park, K.

AU - Kim, J. H.

AU - Bennouna, Jaafar

AU - Chen, Y. M.

AU - Chouaid, C.

AU - De Marinis, Filippo

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, Vikram K.

AU - Planchard, D.

AU - Bagnes, Claudia

AU - Martin, Claudio Marcelo

AU - Recondo, Gonzalo

AU - Zarba, Juan Jose

AU - Blajman, Cesar R.

AU - Richardet, Martín

AU - McLachlan, Sue Anne

AU - Parente, Phillip

AU - Underhill, Craig

AU - Crombie, Catherine

AU - Mainwaring, P.

AU - Greil, Richard

AU - Humblet, Y.

AU - Bustin, Frederique

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 - Zhang, Yiping

AU - Lu, Shun

AU - Zereu, Manuela

AU - Garicochea, Bernardo

AU - Zadra, Cyntia Albuquerque

AU - Riska, Henrik

AU - Alanko, Tuomo

AU - Cadranel, Jacques

AU - Chouaid, Christos

AU - Zalcman, Gérard

AU - Sibilot, Denis Moro

AU - Perol, Maurice

AU - Planchard, David

AU - Bennouna, Jaafar

AU - Fournel, Pierre

AU - Gervais, Radj

AU - Rotarski, Maciej

AU - Coudert, Bruno

AU - Thomas, Michael

AU - Wehler, Thomas

AU - Faehling, Martin

AU - Keilholz, Ulrich

AU - Laack, Eckart

AU - von Pawel, J.

AU - Huber, Rudolf

AU - Dickgreber, Nicolas

AU - Wiewrodt, Rainer

AU - Mark, Z.

AU - Tehenes, S.

AU - Strausz, Janos

AU - Sarosi, Veronika

AU - Prabhash, Kumar

AU - Jain, Minish

AU - Venkatesan, Srinivasan

AU - Sharma, Lalit

AU - Dadhich, Hemant

AU - Nagarkar, Rajnish Vasant

AU - Onn, Amir

AU - Gottfried, Maya

AU - Stemmer, Solomon

AU - Migliorino, M. R.

AU - Grossi, Francesco

AU - Bearz, Alessandra

AU - Bearz, Alessandra

AU - Gridelli, Cesare

AU - Platania, Marco

AU - Platania, Marco

AU - Ceresoli, Giovanni

AU - Cruciani, Giorgio

AU - Delgado, Francisco Gutierrez

AU - Perez, José Luis Gonzalez

AU - Luna, Gabriela Alvarado

AU - Baca, Othon Padilla

AU - Aerts, Joachim

AU - Stigt, Jos

AU - Dingemans, Anne Marie C

AU - Herder, Gerarda

AU - Gans, Steven

AU - Sánchez, Jorge Fernando Salas

AU - Barreda, Renzo Luzgardo Alvarez

AU - Pantigoso, Wilbert Rodriguez

AU - Palomino, Osbert Luis Mejia

AU - Jaskiewicz, Piotr

AU - Kazarnowicz, Andrzej

AU - Serwatowski, P.

AU - Szczesna, Aleksandra

AU - Jassem, J.

AU - Lubennikov, Vladimir

AU - Karaseva, Nina

AU - Orlov, S.

AU - Ragulin, Yuri

AU - Garrido, Pilar

AU - Larriba, José Luis González

AU - Camps, Carlos

AU - Campelo, Rosario García

AU - Lianes, Pilar

AU - Cobo, Manuel

AU - Felip, Enriqueta

AU - Kim, Dong Wan

AU - Kim, Sang We

AU - Park, Keunchil

AU - Kim, Joo Hang

AU - Han, Ji Youn

AU - Kim, Young Chul

AU - Yang, Chih Hsin

AU - Hsia, Te Chun

AU - Chen, Yuh Min

AU - Tsai, Ying Huang

AU - Chang, Gee Chen

AU - Tsao, Thomas Chang Yao

AU - Su, Wu Chou

AU - Huang, Ming Shyan

AU - Ho, Ching Liang

AU - Hsieh, Ruey Kuen

AU - Vinnyk, Yuriy

AU - Popovych, Oleksandr

AU - Ponomarova, Olga

AU - Bondarenko, Igor

AU - Polishchuk, Iryna

AU - Shah, Riyaz

AU - Mitra, Sanka

AU - Popat, Sanjaykumar

AU - Spicer, James

AU - Toy, Elizabeth

AU - Talbot, Toby

AU - Brown, Emma

AU - Upadhyay, Sunil

AU - Summers, Y.

AU - Gurtler, Jayne

AU - Meza, Luis

AU - Thropay, John

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

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

U2 - 10.1093/annonc/mdv597

DO - 10.1093/annonc/mdv597

M3 - Article

VL - 27

SP - 417

EP - 423

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 3

M1 - mdv597

ER -