| 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. |
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(Samsung Medical Center. Sungkyunkwan University School of Medicine)
