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

2015; Elsevier BV; Volume: 27; Issue: 3 Linguagem: Inglês

10.1093/annonc/mdv597

1569-8041

Martin Schüler, James Chih‐Hsin Yang, K. Park, Jie‐Hyun Kim, Jaafar Bennouna, Y.-M. Chen, C. Chouaïd, Filippo de Marinis, Jinlun Feng, Francesco Grossi, D.-W. Kim, X. Liu, Shun Lü, János Strausz, Yuriy Vinnyk, Rainer Wiewrodt, Caicun Zhou, B. Wang, Vikram K. Chand, David Planchard, Sai‐Hong Ignatius Ou, David Planchard, Keunchil Park, Martin Schüler, James Chih‐Hsin Yang, Vikram K. Chand, Klaus Röhr, Claudia Bagnes, Claudio Martín, G. Recondo, Juan José Zarbá, C. Blajman, Martin Eduardo Richardet, Sue‐Anne McLachlan, Phillip Parente, Craig Underhill, Catherine Crombie, Paul N. Mainwaring, Richard Greil, Yves Humblet, F. Bustin, L Carestia, Danny Galdermans, Marc Lambrechts, Laetitia Delval, Piet Vercauter, Caicun Zhou, Jin Wang, Cheng Huang, Xiaoyan Lin, Yi‐Long Wu, Xiaoqing Liu, Ying Cheng, Shukui Qin, Jifeng Feng, Jianjin Huang, Yiping Zhang, Shun Lü, Manuela Zereu, Bernardo Garicochea, Cyntia Albuquerque Zadra, Henrik Riska, Tuomo Alanko, Jacques Cadranel, C. Chouaïd, Gérard Zalcman, Denis Moro‐Sibilot, M. Pérol, David Planchard, Jaafar Bennouna, P. Fournel, Radj Gervais, M. Rotarski, Bruno Coudert, Martin Schüler, Michael Thomas, Thomas Wehler, Martin Faehling, Ulrich Keilholz, Eckart Laack, Joachim von Pawel, Rudolf M. Huber, N Dickgreber, Rainer Wiewrodt, Z. Mark, S. Tehenes, János Strausz, Veronika Sárosi, Kumar Prabhash, Minish Jain, Venkatesan Srinivasan, Lalit Mohan Sharma, H. Dadhich, Rajnish Nagarkar, Amir Onn, Maya Gottfried, Salomon M. Stemmer, Maria Rita Migliorino, Francesco Grossi, Paolo Bidoli, Alessandra Bearz, Cesare Gridelli, Carlo Milandri, Marco Platania, Giovanni Luca Ceresoli, Giorgio Cruciani, Francisco Gutiérrez Delgado, José Luis Gonzalez Perez, Gabriela Alvarado Luna, O. Baca, J. Aerts, J.A. Stigt, Anne‐Marie C. Dingemans, Gerarda J.M. Herder, Steven Gans, Jorge Fernando Salas Sánchez, Renzo Luzgardo Alvarez Barreda, Wilbert Rodriguez Pantigoso, Osbert Luis Mejia Palomino, Piotr Jaśkiewicz, Andrzej Każarnowicz, Piotr Serwatowski, Aleksandra Szczęsna, Jacek Jassem, В. А. Лубенников, Nina Karaseva, С. В. Орлов, Yu. А. Ragulin, Pilar Garrido, J.L. González-Larriba, Carlos Camps, Rosario García Campelo, P. Lianes, Manuel Cobo, Enriqueta Felip, Dong‐Wan Kim, Sang‐We Kim, Keunchil Park, Joo-Hang Kim, Ji‐Youn Han, Young‐Chul Kim, James 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 V. Popovych, Olga Ponomarova, Igor Bondarenko, I I Polishchuk, Riyaz Shah, Sanka Mitra, Sanjaykumar Popat, James Spicer, Elizabeth Toy, Sanjaykumar Popat, Toby Talbot, Emma Brown, Sunil Upadhyay, Yvonne Summers, Jayne Gurtler, Luís Meza, John P. Thropay,

Lung Cancer Research Studies

BackgroundAfatinib 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 methodsPatients 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.ResultsTwo 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.ConclusionAfatinib 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 numberNCT01085136 (clinicaltrials.gov).