Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer
Solange Peters, D Ross Camidge, Alice T Shaw, Shirish Gadgeel, Jin S Ahn, Dong-Wan Kim, Sai-Hong I Ou, Maurice Pérol, Rafal Dziadziuszko, Rafael Rosell, Ali Zeaiter, Emmanuel Mitry, Sophie Golding, Bogdana Balas, Johannes Noe, Peter N Morcos, Tony Mok, ALEX Trial Investigators, I Nordman, K Pittman, R Dear, Z Lwin, P Briggs, N Pavlakis, T Ceric, B Mehic, M Stanetic, F A Franke, G Castro Jr, G Santo Borges, J Pereira, L Brust, L Santos, M Cruz, R Ribeiro, S De Azevedo, Y V Neron, R Sangha, V Cohen, R Burkes, M Abdelsalam, S Yadav, P Cheema, E Yanez, O Aren, C Zhou, L Zhang, X Liu, L Corrales Rodriguez, P Meldgaard, J B Soerensen, T McCulloch, N Rodriguez, R Gaafar, H Abdel Azeem, B Coudert, D Moro-Sibilot, H Lena, J Bennouna, A Cortot, R Veillon, J Cadranel, F Barlesi, M Reck, J Mezger, J von Pawel, J R Fischer, N K Dickgreber, K Zarogoulidis, K Syrigos, V Georgoulias, S Agelaki, H Castro-Salguero, J Ho, S H Chan, C K Cheng, A Ng, S Stemmer, M Wollner, M Gottfried, J Dudnik, A Cyjon, N Heching, S Novello, M Tiseo, M Platania, A Misino, C Gridelli, F Ciardiello, A Favaretto, F De Marinis, F Longo, R Bordonaro, C Dazzi, R Chiari, E Mercuri, E Macedo, J R Rodriguez Cid, M McKeage, L Vera, H D Morón Escobar, M Rodriguez, L Mas, R Ramlau, D Kowalski, A Szczesna, A Kazarnowicz, J Milanowski, J Luboch-Kowal, J Oliveira, F Barata, T Almodovar, J-S Lee, B C Cho, S-W Kim, J-Y Han, N Karaseva, D Stroyakovskii, A Kuzmin, A Smolin, K Laktionov, Y Ragulin, A Filippov, E Levchenko, D Jovanovic, B Perin, Z Andric, R Soo, E H Tan, J De Castro Carpeno, M Provencio Pulla, P Garrido Lopez, E Felip Font, T Morano Bueno, A Sanchez, D Isla Casado, S Ponce Aix, N Reguart Aransay, S Viteri Ramirez, D Rodriguez Abreu, J M Sanchez Torres, B Massuti Sureda, M Ramos Vazquez, J M Tabernero, A Curioni, S Rothschild, A Scherz, C-H Chiu, W-C Su, C-H J Yang, G-C Chang, T-C Hsia, C-T Yang, E Tharavichitkul, P Pongthai, W Arpornwirat, S Geater, V Srimuninnimit, V Sriuranpong, A Demirkazik, E Goker, H Harputluoglu, I Cicin, F Kose, M Erman, I Bondarenko, Y Vinnyk, Y Shparyk, Y Golovko, R Lal, M Forster, R Califano, G Skailes, J Thompson, T Mekhail, J Polikoff, D Spigel, S Waqar, R Hermann, E Deo, G Simon, I Rybkin, P R Kaywin, J Uyeki, M Gubens, S Limaye, D E Gerber, T Leal, A I Spira, L Bazhenova, J Cetnar, M Socinski, M Jahanzeb, F Kabbinavar, W E Lawler, M R Hancock, L E Raez, B A DiCarlo, T E Lowe, M Fidler, H Ross, S J Davidson, J D Sanchez, J Hamm, S Kerr, N Belman, S Baker, B Naraev, G Jung, M Edelman, L Feldman, C Belani, S Pakkala, Solange Peters, D Ross Camidge, Alice T Shaw, Shirish Gadgeel, Jin S Ahn, Dong-Wan Kim, Sai-Hong I Ou, Maurice Pérol, Rafal Dziadziuszko, Rafael Rosell, Ali Zeaiter, Emmanuel Mitry, Sophie Golding, Bogdana Balas, Johannes Noe, Peter N Morcos, Tony Mok, ALEX Trial Investigators, I Nordman, K Pittman, R Dear, Z Lwin, P Briggs, N Pavlakis, T Ceric, B Mehic, M Stanetic, F A Franke, G Castro Jr, G Santo Borges, J Pereira, L Brust, L Santos, M Cruz, R Ribeiro, S De Azevedo, Y V Neron, R Sangha, V Cohen, R Burkes, M Abdelsalam, S Yadav, P Cheema, E Yanez, O Aren, C Zhou, L Zhang, X Liu, L Corrales Rodriguez, P Meldgaard, J B Soerensen, T McCulloch, N Rodriguez, R Gaafar, H Abdel Azeem, B Coudert, D Moro-Sibilot, H Lena, J Bennouna, A Cortot, R Veillon, J Cadranel, F Barlesi, M Reck, J Mezger, J von Pawel, J R Fischer, N K Dickgreber, K Zarogoulidis, K Syrigos, V Georgoulias, S Agelaki, H Castro-Salguero, J Ho, S H Chan, C K Cheng, A Ng, S Stemmer, M Wollner, M Gottfried, J Dudnik, A Cyjon, N Heching, S Novello, M Tiseo, M Platania, A Misino, C Gridelli, F Ciardiello, A Favaretto, F De Marinis, F Longo, R Bordonaro, C Dazzi, R Chiari, E Mercuri, E Macedo, J R Rodriguez Cid, M McKeage, L Vera, H D Morón Escobar, M Rodriguez, L Mas, R Ramlau, D Kowalski, A Szczesna, A Kazarnowicz, J Milanowski, J Luboch-Kowal, J Oliveira, F Barata, T Almodovar, J-S Lee, B C Cho, S-W Kim, J-Y Han, N Karaseva, D Stroyakovskii, A Kuzmin, A Smolin, K Laktionov, Y Ragulin, A Filippov, E Levchenko, D Jovanovic, B Perin, Z Andric, R Soo, E H Tan, J De Castro Carpeno, M Provencio Pulla, P Garrido Lopez, E Felip Font, T Morano Bueno, A Sanchez, D Isla Casado, S Ponce Aix, N Reguart Aransay, S Viteri Ramirez, D Rodriguez Abreu, J M Sanchez Torres, B Massuti Sureda, M Ramos Vazquez, J M Tabernero, A Curioni, S Rothschild, A Scherz, C-H Chiu, W-C Su, C-H J Yang, G-C Chang, T-C Hsia, C-T Yang, E Tharavichitkul, P Pongthai, W Arpornwirat, S Geater, V Srimuninnimit, V Sriuranpong, A Demirkazik, E Goker, H Harputluoglu, I Cicin, F Kose, M Erman, I Bondarenko, Y Vinnyk, Y Shparyk, Y Golovko, R Lal, M Forster, R Califano, G Skailes, J Thompson, T Mekhail, J Polikoff, D Spigel, S Waqar, R Hermann, E Deo, G Simon, I Rybkin, P R Kaywin, J Uyeki, M Gubens, S Limaye, D E Gerber, T Leal, A I Spira, L Bazhenova, J Cetnar, M Socinski, M Jahanzeb, F Kabbinavar, W E Lawler, M R Hancock, L E Raez, B A DiCarlo, T E Lowe, M Fidler, H Ross, S J Davidson, J D Sanchez, J Hamm, S Kerr, N Belman, S Baker, B Naraev, G Jung, M Edelman, L Feldman, C Belani, S Pakkala
Abstract
Background: Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease.
Methods: In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival. Secondary end points were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival.
Results: During a median follow-up of 17.6 months (crizotinib) and 18.6 months (alectinib), an event of disease progression or death occurred in 62 of 152 patients (41%) in the alectinib group and 102 of 151 patients (68%) in the crizotinib group. The rate of investigator-assessed progression-free survival was significantly higher with alectinib than with crizotinib (12-month event-free survival rate, 68.4% [95% confidence interval (CI), 61.0 to 75.9] with alectinib vs. 48.7% [95% CI, 40.4 to 56.9] with crizotinib; hazard ratio for disease progression or death, 0.47 [95% CI, 0.34 to 0.65]; P<0.001); the median progression-free survival with alectinib was not reached. The results for independent review committee-assessed progression-free survival were consistent with those for the primary end point. A total of 18 patients (12%) in the alectinib group had an event of CNS progression, as compared with 68 patients (45%) in the crizotinib group (cause-specific hazard ratio, 0.16; 95% CI, 0.10 to 0.28; P<0.001). A response occurred in 126 patients in the alectinib group (response rate, 82.9%; 95% CI, 76.0 to 88.5) and in 114 patients in the crizotinib group (response rate, 75.5%; 95% CI, 67.8 to 82.1) (P=0.09). Grade 3 to 5 adverse events were less frequent with alectinib (41% vs. 50% with crizotinib).
Conclusions: As compared with crizotinib, alectinib showed superior efficacy and lower toxicity in primary treatment of ALK-positive NSCLC. (Funded by F. Hoffmann-La Roche; ALEX ClinicalTrials.gov number, NCT02075840 .).
Source: PubMed