1. Alectinib versus Crizotinib in Untreated ALK-Positive Non–Small-Cell Lung Cancer
- Author
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Rafael Rosell, Alice T. Shaw, Ali Zeaiter, Shirish M. Gadgeel, Emmanuel Mitry, Bogdana Balas, Jin S. Ahn, Maurice Perol, Johannes Noe, Sai-Hong Ignatius Ou, Peter N. Morcos, D. Ross Camidge, Solange Peters, Tony Mok, Dong Wan Kim, Rafal Dziadziuszko, Sophie Golding, 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., and Pakkala, S.
- Subjects
Adult ,Male ,0301 basic medicine ,Oncology ,Alectinib ,medicine.medical_specialty ,Pathology ,Lung Neoplasms ,Brigatinib ,Pyridines ,medicine.drug_class ,Carbazoles ,Antineoplastic Agents ,Kaplan-Meier Estimate ,Aged, 80 and over ,Animals ,Antineoplastic Agents/adverse effects ,Antineoplastic Agents/therapeutic use ,Carbazoles/adverse effects ,Carbazoles/therapeutic use ,Carcinoma, Non-Small-Cell Lung/drug therapy ,Carcinoma, Non-Small-Cell Lung/mortality ,Central Nervous System Neoplasms/drug therapy ,Central Nervous System Neoplasms/secondary ,Disease-Free Survival ,Female ,Follow-Up Studies ,Humans ,Intention to Treat Analysis ,Lung Neoplasms/drug therapy ,Lung Neoplasms/mortality ,Middle Aged ,Piperidines/adverse effects ,Piperidines/therapeutic use ,Protein Kinase Inhibitors/adverse effects ,Protein Kinase Inhibitors/therapeutic use ,Pyrazoles/adverse effects ,Pyrazoles/therapeutic use ,Pyridines/adverse effects ,Pyridines/therapeutic use ,Receptor Protein-Tyrosine Kinases/analysis ,Receptor Protein-Tyrosine Kinases/antagonists & inhibitors ,Young Adult ,Central Nervous System Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Piperidines ,Carcinoma, Non-Small-Cell Lung ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Anaplastic lymphoma kinase ,Lung cancer ,Protein Kinase Inhibitors ,Crizotinib ,Ceritinib ,business.industry ,Receptor Protein-Tyrosine Kinases ,General Medicine ,medicine.disease ,Lorlatinib ,ALK inhibitor ,030104 developmental biology ,030220 oncology & carcinogenesis ,Pyrazoles ,business ,medicine.drug - 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
- Published
- 2017
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