About 5% of the NSCLC patients carry ALK oncogene fusion rearrangement. ALK-targeted inhibitors, for instance, crizotinib, has been approved for ALK-positive NSCLC treatment and is superior to chemotherapy in both first and second-line treatment. However, the cancer typically relapses within a year by acquiring resistance to ALK inhibitors due to mutations in the ALK gene or by bypassing the ALK signaling pathway to other growth or survival pathways. In a phase III trial (ALEX), scientists compared the therapeutic efficacy of the novel ALK-targeted inhibitor, alectinib, with crizotinib in 303 previously untreated ALK-positive NSCLC patients. At the time of analysis, the progression-free survival of patients assigned to receive alectinib was significantly higher than patients assigned to receive crizotinib (12-month event-free survival rate, 68.4%, vs. 48.7%, hazard ratio: 0.47). Median PFS assessed by an independent review committee (IRC) was also significantly longer for those received alectinib than those received crizotinib (25.7 months versus 10.4 months, hazard ratio: 0.50). Among those patients who had measurable CNS progression, 18 patients (12%) were in the alectinib group and 68 patients (45%) were in the crizotinib group (hazard ratio: 0.16). The objective response rates (ORR) were 82.9% in the alectinib group and 75.5% in the crizotinib group (P = 0.09). The adverse events of grade 3 to 5 were 41% in the alectinib group and 50% in the crizotinib group. These results show that alectinib increases progression-free survival (PFS) and with lower toxicity than crizotinib in primary treatment of ALK-positive NSCLC.
Peters S, Camidge DR, Shaw AT, et al., N Engl J Med. 2017 Jun 6.