GoTriple - Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer.

authors

Contributors

ALEX Trial Investigators,

Nordman, I.,

Pittman, K.,

Dear, R.,

Lwin, Z.,

Briggs, P.,

Pavlakis, N.,

Ceric, T.,

Mehic, B.,

Stanetic, M.,

Franke, F.A.,

Castro, G.,

Santo Borges, G.,

Pereira, J.,

Brust, L.,

Santos, L.,

Cruz, M.,

Ribeiro, R.,

De Azevedo, S.,

Neron, Y.V.,

Sangha, R.,

Cohen, V.,

Burkes, R.,

Abdelsalam, M.,

Yadav, S.,

Cheema, P.,

Yanez, E.,

Aren, O.,

Zhou, C.,

Zhang, L.,

Liu, X.,

Corrales Rodriguez, L.,

Meldgaard, P.,

Soerensen, J.B.,

McCulloch, T.,

Rodriguez, N.,

Gaafar, R.,

Abdel Azeem, H.,

Coudert, B.,

Moro-Sibilot, D.,

Lena, H.,

Bennouna, J.,

Cortot, A.,

Veillon, R.,

Cadranel, J.,

Barlesi, F.,

Reck, M.,

Mezger, J.,

von Pawel, J.,

Fischer, J.R.,

Dickgreber, N.K.,

Zarogoulidis, K.,

Syrigos, K.,

Georgoulias, V.,

Agelaki, S.,

Castro-Salguero, H.,

Ho, J.,

Chan, S.H.,

Cheng, C.K.,

Ng, A.,

Stemmer, S.,

Wollner, M.,

Gottfried, M.,

Dudnik, J.,

Cyjon, A.,

Heching, N.,

Novello, S.,

Tiseo, M.,

Platania, M.,

Misino, A.,

Gridelli, C.,

Ciardiello, F.,

Favaretto, A.,

De Marinis, F.,

Longo, F.,

Bordonaro, R.,

Dazzi, C.,

Chiari, R.,

Mercuri, E.,

Macedo, E.,

Rodriguez Cid, J.R.,

McKeage, M.,

Vera, L.,

Morón Escobar, H.D.,

Rodriguez, M.,

Mas, L.,

Ramlau, R.,

Kowalski, D.,

Szczesna, A.,

Kazarnowicz, A.,

Milanowski, J.,

Luboch-Kowal, J.,

Oliveira, J.,

Barata, F.,

Almodovar, T.,

Lee, J.S.,

Cho, B.C.,

Kim, S.W.,

Han, J.Y.,

Karaseva, N.,

Stroyakovskii, D.,

Kuzmin, A.,

Smolin, A.,

Laktionov, K.,

Ragulin, Y.,

Filippov, A.,

Levchenko, E.,

Jovanovic, D.,

Perin, B.,

Andric, Z.,

Soo, R.,

Tan, E.H.,

De Castro Carpeno, J.,

Provencio Pulla, M.,

Garrido Lopez, P.,

Felip Font, E.,

Morano Bueno, T.,

Sanchez, A.,

Isla Casado, D.,

Ponce Aix, S.,

Reguart Aransay, N.,

Viteri Ramirez, S.,

Rodriguez Abreu, D.,

Sanchez Torres, J.M.,

Massuti Sureda, B.,

Ramos Vazquez, M.,

Tabernero, J.M.,

Curioni, A.,

Rothschild, S.,

Scherz, A.,

Chiu, C.H.,

Su, W.C.,

Yang, CHJ,

Chang, G.C.,

Hsia, T.C.,

Yang, C.T.,

Tharavichitkul, E.,

Pongthai, P.,

Arpornwirat, W.,

Geater, S.,

Srimuninnimit, V.,

Sriuranpong, V.,

Demirkazik, A.,

Goker, E.,

Harputluoglu, H.,

Cicin, I.,

Kose, F.,

Erman, M.,

Bondarenko, I.,

Vinnyk, Y.,

Shparyk, Y.,

Golovko, Y.,

Lal, R.,

Forster, M.,

Califano, R.,

Skailes, G.,

Thompson, J.,

Mekhail, T.,

Polikoff, J.,

Spigel, D.,

Waqar, S.,

Hermann, R.,

Deo, E.,

Simon, G.,

Rybkin, I.,

Kaywin, P.R.,

Uyeki, J.,

Gubens, M.,

Limaye, S.,

Gerber, D.E.,

Leal, T.,

Spira, A.I.,

Bazhenova, L.,

Cetnar, J.,

Socinski, M.,

Jahanzeb, M.,

Kabbinavar, F.,

Lawler, W.E.,

Hancock, M.R.,

Raez, L.E.,

DiCarlo, B.A.,

Lowe, T.E.,

Fidler, M.,

Ross, H.,

Davidson, S.J.,

Sanchez, J.D.,

Hamm, J.,

Kerr, S.,

Belman, N.,

Baker, S.,

Naraev, B.,

Jung, G.,

Edelman, M.,

Feldman, L.,

Belani, C.,

Pakkala, S.

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Abstract

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. 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. 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). 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 .).