Frontline Alectinib Approved in Europe for ALK-Positive NSCLC

Jason M. Broderick

Dr. Sandra Horning
Sandra Horning, MD
The European Commission (EC) has approved alectinib (Alecensa) for the frontline treatment of patients with ALK-positive metastatic non–small cell lung cancer (NSCLC), according to Roche, the manufacturer of the second-generation ALK inhibitor.

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; HR, 0.47; 95% CI, 0.34-0.65; P <.001). 

“Many ALK-positive lung cancer patients see their disease progress within a year on current treatments,” Sandra Horning, MD, chief medical officer and head of Global Product Development, Roche, said in a statement. “The EU approval of Alecensa heralds a new era for these patients, who now have a treatment option available that halves the risk of disease progression compared with the previous standard of care, crizotinib, and is also highly effective against brain metastases.”

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 PFS 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 <.001).

The overall response rate (ORR) with alectinib was 79% (95% CI, 72-85) versus 72% (95% CI, 64-79) with crizotinib (P = .1652). The complete response rates were 13% versus 6%, respectively, and the partial response rate was 66% in both arms.

Eighty-two percent of patients receiving alectinib had a response duration ≥6 months, with 64% and 37%, having response durations ≥12 months and ≥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 <.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 (AEs). In ALEX, 41% of patients assigned to alectinib experienced grade ≥3 AEs compared with 50% in the crizotinib group. Additionally, AEs leading to discontinuation (11% vs 13%), dose reduction (16% vs 21%), and dose interruption (19% vs 25%) were all lower with alectinib.

Alectinib was previously approved for frontline ALK-positive NSCLC in the United States, Japan, and Turkey.
European Commission approves Roche’s Alecensa (alectinib) as first-line treatment in ALK-positive lung cancer. Roche. Available at: Accessed December 22, 2017.
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