학술논문
Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial
Document Type
Academic Journal
Author
Schuler, M.; Yang, J. C.-H.; 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.; Ignatius Ou, Sai Hong; Planchard, David; Park, Keunchil; Schuler, Martin; Yang, James; Chand, Vikram; Rohr, Klaus; Bagnes, Claudia; Martin, Claudio Marcelo; Recondo, Gonzalo; Zarba, Juan Jose; Blajman, Cesar; Richardet, Martín; McLachlan, Sue-Anne; Parente, Phillip; Underhill, Craig; Crombie, Catherine; Mainwaring, Paul; Greil, Richard; Humblet, Yves; Bustin, Frédérique; 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; Schuler, Martin; Thomas, Michael; Wehler, Thomas; Faehling, Martin; Keilholz, Ulrich; Laack, Eckart; von Pawel, Joachim; Huber, Rudolf; Dickgreber, Nicolas; Wiewrodt, Rainer; Mark, Zsuzsanna; Tehenes, Sandor; Strausz, Janos; Sarosi, Veronika; Prabhash, Kumar; Jain, Minish; Venkatesan, Srinivasan; Sharma, Lalit; Dadhich, Hemant; Nagarkar, Rajnish Vasant; Onn, Amir; Gottfried, Maya; Stemmer, Solomon; Migliorino, Maria Rita; Grossi, Francesco; Bidoli, Paolo; Bearz, Alessandra; Gridelli, Cesare; Milandri, Carlo; Platania, Marco; Ceresoli, Giovanni Luca; Cruciani, Giorgio; Delgado, Francisco Gutierrez; Gonzalez Perez, José Luis; Luna, Gabriela Alvarado; Baca, Othon Padilla; Aerts, J.G.J.V.; Stigt, J.A.; Dingemans, A.M.C.; Herder, G.J.M.; Gans, S. J. M.; Salas Sánchez, Jorge Fernando; Alvarez Barreda, Renzo Luzgardo; Pantigoso, Wilbert Rodriguez; Palomino, Osbert Luis Mejia; Jaskiewicz, Piotr; Kazarnowicz, Andrzej; Serwatowski, Piotr; Szczesna, Aleksandra; Jassem, Jacek; Lubennikov, Vladimir; Karaseva, Nina; Orlov, Sergey; Ragulin, Yuri; Garrido, Pilar; González Larriba, José Luis; 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; Popat, Sanjaykumar; Talbot, Toby; Brown, Emma; Upadhyay, Sunil; Summers, Yvonne; Gurtler, Jayne; Meza, Luis; Thropay, John
Source
Annals of Oncology. Mar 01, 2016 27(3):417-423
Subject
Language
English
ISSN
0923-7534
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/m/week) or investigatorʼs 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).