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

被引:1887
作者
Peters, Solange [1 ]
Camidge, D. Ross [3 ]
Shaw, Alice T. [4 ]
Gadgeel, Shirish [5 ]
Ahn, Jin S. [6 ]
Kim, Dong-Wan [7 ]
Ou, Sai-Hong I. [8 ]
Perol, Maurice [9 ]
Dziadziuszko, Rafal [10 ]
Rosell, Rafael [11 ]
Zeaiter, Ali [2 ]
Mitry, Emmanuel [2 ]
Golding, Sophie [2 ]
Balas, Bogdana [2 ]
Noe, Johannes [2 ]
Morcos, Peter N. [12 ]
Mok, Tony [13 ]
机构
[1] Lausanne Univ Hosp, Lausanne, Switzerland
[2] F Hoffmann La Roche, Basel, Switzerland
[3] Univ Colorado, Denver, CO 80202 USA
[4] Massachusetts Gen Hosp, Boston, MA 02114 USA
[5] Univ Michigan, Ann Arbor, MI 48109 USA
[6] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea
[7] Seoul Natl Univ Hosp, Seoul, South Korea
[8] Univ Calif Irvine, Sch Med, Chao Family Comprehens Canc Ctr, Orange, CA 92668 USA
[9] Leon Berard Canc Ctr, Dept Med Oncol, Lyon, France
[10] Med Univ Gdansk, Dept Oncol & Radiotherapy, Gdansk, Poland
[11] Catalan Inst Oncol, Barcelona, Spain
[12] Roche Innovat Ctr, New York, NY USA
[13] Chinese Univ Hong Kong, State Key Lab South China, Hong Kong, Hong Kong, Peoples R China
关键词
INHIBITOR ALECTINIB; ANTITUMOR-ACTIVITY; CHEMOTHERAPY; RESISTANT; MODELS;
D O I
10.1056/NEJMoa1704795
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.)
引用
收藏
页码:829 / 838
页数:10
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