Alectinib

In an open-label, randomized, phase III study (the ALEX trial [NCT02075840]), 303 patients with previously untreated, advanced ALK-rearranged NSCLC received either alectinib (600 mg twice a day) or crizotinib (250 mg twice a day).[64] The primary end point was investigator-assessed PFS.

In an open-label, randomized, phase III study (the ALEX trial [NCT02075840]), 303 patients with previously untreated, advanced ALK-rearranged NSCLC received either alectinib (600 mg twice a day) or crizotinib (250 mg twice a day).[64] The primary end point was investigator-assessed PFS.

The rate of PFS was significantly higher with alectinib than crizotinib; the 12-month event-free survival rate was 68.4% for the alectinib group (95% CI, 61.0%–75.9%) compared with 48.7% for the crizotinib group (95% CI, 40.4%–56.9%) (HR, 0.47; 95% CI, 0.34–0.65; P < .001). The median PFS was not reached with alectinib. The results of independent review committee-assessed PFS were consistent.[64][Level of evidence B1]

In an open-label, randomized, phase III study (the ALEX trial [NCT02075840]), 303 patients with previously untreated, advanced ALK-rearranged NSCLC received either alectinib (600 mg twice a day) or crizotinib (250 mg twice a day).[64] The primary end point was investigator-assessed PFS.

CNS progression events were less frequent with alectinib (12%) than with crizotinib (45%) (HR, 0.16; 95% CI, 0.10–0.28; P <.001).

In an open-label, randomized, phase III study (the ALEX trial [NCT02075840]), 303 patients with previously untreated, advanced ALK-rearranged NSCLC received either alectinib (600 mg twice a day) or crizotinib (250 mg twice a day).[64] The primary end point was investigator-assessed PFS.

The response rate was similar for both groups, 82.9% for the alectinib group compared with 75.5% for the crizotinib group (P = .09).

In an open-label, randomized, phase III study (the ALEX trial [NCT02075840]), 303 patients with previously untreated, advanced ALK-rearranged NSCLC received either alectinib (600 mg twice a day) or crizotinib (250 mg twice a day).[64] The primary end point was investigator-assessed PFS.

Grade 3 to 5 adverse events were less frequent with alectinib (41%) than with crizotinib (50%).

A second, open-label, randomized, phase III trial (J-ALEX) recruited 207 ALK-inhibitor–naïve Japanese patients with ALK-positive NSCLC who were chemotherapy-naïve or had received one previous chemotherapy regimen. Patients were randomly assigned in a 1:1 ratio to receive alectinib (300 mg twice daily, which is the dose approved in Japan and is lower than the 600 mg twice daily dose approved elsewhere) versus crizotinib (250 mg twice daily).[65] The primary end point was PFS-assessed by an independent review committee.

A second, open-label, randomized, phase III trial (J-ALEX) recruited 207 ALK-inhibitor–naïve Japanese patients with ALK-positive NSCLC who were chemotherapy-naïve or had received one previous chemotherapy regimen. Patients were randomly assigned in a 1:1 ratio to receive alectinib (300 mg twice daily, which is the dose approved in Japan and is lower than the 600 mg twice daily dose approved elsewhere) versus crizotinib (250 mg twice daily).[65] The primary end point was PFS-assessed by an independent review committee.

At data cutoff for the second primary interim analysis, the independent data monitoring committee determined that the primary end point was met (HR, 0.34; 99.7% CI, 0.17–0.71; P <.0001) and recommended immediate release of the data. Median PFS had not been reached with alectinib but was reached at 10.2 months with crizotinib.

A second, open-label, randomized, phase III trial (J-ALEX) recruited 207 ALK-inhibitor–naïve Japanese patients with ALK-positive NSCLC who were chemotherapy-naïve or had received one previous chemotherapy regimen. Patients were randomly assigned in a 1:1 ratio to receive alectinib (300 mg twice daily, which is the dose approved in Japan and is lower than the 600 mg twice daily dose approved elsewhere) versus crizotinib (250 mg twice daily).[65] The primary end point was PFS-assessed by an independent review committee.

Grade 3 or 4 adverse events occurred less frequently with alectinib (26% occurrence rate) than with crizotinib (52% occurrence rate).