Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial
Authors: M. Schuler, J.C.-H. Yang, K. Park, J.-H. Kim, J. Bennouna, Y.-M. Chen, C. Chouaid, F. De Marinis, J.-F. Feng, F. Grossi, D.-W. Kim, X. Liu, S. Lu, J. Strausz, Y. Vinnyk, R. Wiewrodt, C. Zhou, B. Wang, V.K. Chand, D. Planchard, SaiHong Ignatius Ou, David Planchard, Keunchil Park, Martin Schuler, James Yang, Vikram Chand, Klaus Rohr, Claudia Bagnes, Claudio Marcelo Martin, Gonzalo Recondo, Juan Jose Zarba, Cesar Blajman, Martín Richardet, Sue-Anne McLachlan, Phillip Parente, Craig Underhill, Catherine Crombie, Paul Mainwaring, Richard Greil, Yves Humblet, Frédérique 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, Martin Schuler, Michael Thomas, Thomas Wehler, Martin Faehling, Ulrich Keilholz, Eckart Laack, Joachim von Pawel, Rudolf Huber, Nicolas Dickgreber, Rainer Wiewrodt, Zsuzsanna Mark, Sandor Tehenes, Janos Strausz, Veronika Sarosi, Kumar Prabhash, Minish Jain, Srinivasan Venkatesan, Lalit Sharma, Hemant Dadhich, Rajnish Vasant Nagarkar, Amir Onn, Maya Gottfried, Solomon Stemmer, Maria Rita Migliorino, Francesco Grossi, Paolo Bidoli, Alessandra Bearz, Cesare Gridelli, Carlo Milandri, Marco Platania, Giovanni Luca Ceresoli, Giorgio Cruciani, Francisco Gutierrez Delgado, José Luis Gonzalez Perez, Gabriela Alvarado Luna, Othon Padilla Baca, J.G.J.V. Aerts, J.A. Stigt, A.M.C. Dingemans, G.J.M. Herder, S.J.M. Gans, Jorge Fernando Salas Sánchez, Renzo Luzgardo Alvarez Barreda, Wilbert Rodriguez Pantigoso, Osbert Luis Mejia Palomino, Piotr Jaskiewicz, Andrzej Kazarnowicz, Piotr Serwatowski, Aleksandra Szczesna, Jacek Jassem, Vladimir Lubennikov, Nina Karaseva, Sergey 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, Sanjaykumar Popat, Toby Talbot, Emma Brown, Sunil Upadhyay, Yvonne Summers, Jayne Gurtler, Luis Meza, John Thropay
Journal: Annals of Oncology (2015)

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).