The European Commission ( EC ) has approved Alecensa ( Alectinib ), a second-generation ALK inhibitor, for the frontline treatment of patients with ALK-positive metastatic non–small cell lung cancer ( NSCLC ).
The approval, which follows a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use, is based on findings from the phase III ALEX trial.
In the study, Alectinib reduced the risk of disease progression or death by 53% compared with Crizotinib ( Xalkori ) ( hazard ratio, HR=0.47; 95% CI, 0.34-0.65; P less than 0.001 ).
Beyond the first-line approval, the EC has also converted Alectinib’s conditional marketing authorization for second-line treatment after progression on Crizotinib to a standard marketing authorization.
In the ALEX trial, researchers at 161 locations in 31 countries randomly assigned treatment-naïve patients to twice daily dosages of 600 mg of Alectinib ( n=152 ) or 250 mg of Crizotinib ( n=151 ).
The investigator-assessed median progression-free survival was not reached in the Alectinib arm versus 11.1 months in the Crizotinib group.
By independent review, the medians were 25.7 months versus 10.4 months, respectively ( HR, 0.50; 95% CI, 0.36-0.70; P less than 0.001 ).
The overall response rate ( ORR ) with Alectinib was 79% ( 95% CI, 72-85 ) versus 72% ( 95% CI, 64-79 ) with Crizotinib ( P = 0.1652 ).
The complete response rates were 13% versus 6%, respectively, and the partial response rate was 66% in both arms.
82% of patients receiving Alectinib had a response duration greater than or equal to 6 months, with 64% and 37%, having response durations greater than or equal to 12 months and greater than or equal to 18 months, respectively.
The corresponding rates in the Crizotinib arm were 57%, 36%, and 14%.
Alectinib reduced the risk for progression in the CNS by 84% compared with Crizotinib ( HR, 0.16; 95% CI, 0.10-0.28; P less than 0.001 ).
The 12-month cumulative rate of CNS progression for people with or without existing CNS metastases at baseline was 9.4% ( 95% CI, 5.4-14.7 ) in the Alectinib arm and 41.4% ( 95% CI, 33.2-49.4 ) for Crizotinib.
The CNS ORR was 81% ( 95% CI, 58-95 ) in the Alectinib arm versus 50% ( 95% CI, 28-72 ) in the Crizotinib arm.
The complete response rates were 38% versus 5%, respectively. CNS response duration was 12 months or longer in 59% of the Crizotinib group versus 36% of the Alectinib group.
Alectinib was associated with fewer serious adverse events. In ALEX, 41% of patients assigned to Alectinib experienced grade greater than or equal to 3 adverse effects compared with 50% in the Crizotinib group. br> Additionally, adverse reactions leading to discontinuation ( 11% vs 13% ), dose reduction ( 16% vs 21% ), and dose interruption ( 19% vs 25% ) were all lower with Alectinib. ( Xagena )
Source: Roche, 2017