Alectinib Approved in China for ALK+ NSCLC

The China National Drug Administration has approved alectinib for the treatment of patients with ALK-positive, advanced non–small cell lung cancer.

Sandra Horning, MD

The China National Drug Administration (CNDA) has approved alectinib (Alecensa) for the treatment of patients with ALK-positive, advanced non—small cell lung cancer (NSCLC), according to Roche, the manufacturer of the second-generation ALK inhibitor.

The approval was based on the primary analysis of the phase III ALEX study, in which frontline alectinib reduced the risk of disease progression or death by 53% versus crizotinib in patients with ALK-positive NSCLC (HR, 0.47; 95% CI, 0.34-0.65; P <.0001). The investigator-assessed median progression-free survival (PFS) had not been reached in the alectinib arm (95% CI, 17.7-not reached) versus 11.1 months (95% CI, 9.1-13.1) in the crizotinib arm. The median PFS per independent review was 25.7 months (95% CI, 19.9&#8210;not reached) versus 10.4 months (95% CI, 7.7-14.6), respectively (HR, 0.50; 95% CI, 0.36-0.70; P <.0001).

There was also an 84% reduction in the risk of progression in the CNS with alectinib versus crizotinib (HR, 0.16, 95% CI, 0.10-0.28; P <.0001). Among patients with and without CNS metastases at baseline, the 12-month cumulative rate of CNS progression was 9.4% (95% CI, 5.4%-14.7%) compared with 41.4% (95% CI: 33.2%-49.4%) for the crizotinib arm. Overall survival data were not yet mature.

Updated data presented at the ASCO Annual Meeting in June 2018 showed that the median PFS per investigator assessment was 34.8 months (95% CI, 17.7-NE) with alectinib versus 10.9 months (95% CI, 9.1-12.9) with crizotinib. There was a 57% reduction in the risk of disease progression or death for the alectinib arm (HR, 0.43; 95% CI 0.32-0.58).

The CNDA also reviewed pharmacokinetic data for Asian patients enrolled in the phase III ALESIA study, which also compared alectinib and crizotinib in frontline ALK-positive NSCLC, as well as findings from 2 phase II studies evaluating alectinib in patients after the failure of crizotinib.

“Today’s approval marks a new era for ALK-positive lung cancer patients in China, who now have a treatment option that offers a meaningful, sustained benefit compared with the previous standard of care,” Sandra Horning, MD, Roche’s chief medical officer and head of Global Product Development, said in a statement.

“It also represents a significant regulatory shift, with the approval received under unprecedented timelines. We are proud to be at the forefront of healthcare innovation in China by helping to bring Alecensa to patients as quickly as possible,” added Horning.

In the open-label ALEX study, patients were randomized to 600 mg of alectinib (n = 152) or 250 mg of crizotinib (n = 151), both twice daily. The updated data shared at the 2018 ASCO Annual Meeting showed that the objective response rate was 82.9% versus 75.5% with alectinib versus crizotinib, respectively.

The PFS benefit with alectinib was observed regardless of CNS metastases status at baseline. Per investigator assessment, the median PFS in patients without CNS metastases was 34.8 months with alectinib compared with 14.7 months with crizotinib (HR, 0.47; 95% CI, 0.32-0.71). Among those with CNS metastases, the median PFS was 27.7 months versus 7.4 months, respectively (HR, 0.35; 95% CI, 0.22-0.56).

There were fewer grade 3 to 5 adverse events (AEs) reported with alectinib (44.7%) versus crizotinib (51.0%). Serious AEs occurring in ≥2% of the alectinib arm included acute kidney injury (2.6%) and anemia (2.0%). Dose reductions (16.4% vs. 20.5%) and interruptions (22.4% vs. 25.2%) were lower with alectinib compared with crizotinib. The rate of AE-related discontinuations (13.2%) was the same in both arms.

China National Drug Administration grants rapid approval of Roche’s Alecensa (alectinib) as a treatment for ALK-positive lung cancer. Roche. Published August 20, 2018. Accessed August 21, 2018.