Alecensa (alectinib) significantly reduced the risk of disease worsening or death by more than half (53%) compared to first-line treatment for people with ALK-positive advanced NSCLC.-Genentech/Roche

At ASCO 2017 Genentech/Roche presentation: Alecensa (alectinib) significantly reduced the risk of disease worsening or death (progression-free survival, PFS) by more than half (53%) compared to crizotinib (Xalkori) when given as initial (first-line) treatment for people with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) (hazard ratio (HR)=0.47, 95% CI: 0.34-0.65, p<0.0001).

Median PFS reported by the investigators, the primary endpoint of the study, was not yet reached in people who received Alecensa (95% CI: 17.7-not reached) versus 11.1 months (95% CI: 9.1-13.1 months) in those who received crizotinib. Median PFS assessed by an independent review committee (IRC), a secondary endpoint, was 25.7 months (95% CI: 19.9-not reached) for people who received Alecensa versus 10.4 months (95% CI: 7.7-14.6 months) for people who received crizotinib (HR=0.50, 95% CI 0.36–0.70; p<0.0001). The safety profile of Alecensa was consistent with that observed in previous studies.

Overall survival (OS) data are currently considered immature with only about a quarter of events being reported. Grade 3-5 adverse events (AEs) were less frequent in the Alecensa arm (41%) compared to the crizotinib arm (50%). In the Alecensa arm, the most common Grade 3-5 AEs were increased liver enzymes (alanine transferase and aspartate transferase; 5%) and decreased red blood cells (anaemia; 5%). AEs leading to discontinuation (11% vs. 13%), dose reduction (16% vs. 21%) and dose interruption (19% vs. 25%) were all lower in the Alecensa arm compared to the crizotinib arm.

The global, randomised phase III ALEX study also demonstrated that Alecensa reduced the risk of disease progression in the central nervous system (CNS) by 84% (HR=0.16, 95% CI: 0.10-0.28; p<0.0001). 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%) for people treated with Alecensa and 41.4% (95% CI: 33.2-49.4%) for people treated with crizotinib.

“Alecensa reduced the risk of disease progression by more than half and reduced the risk of cancer spreading to or growing in the brain, which can have devastating effects for patients,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “These results significantly improve upon the standard of care for this disease, extending the average time that people lived without their disease worsening from less than a year to more than two years. We are submitting these data to regulatory authorities around the world.”

See- "Alectinib versus Crizotinib in Untreated ALK-Positive Non–Small-Cell Lung Cancer"-Solange Peters, M.D., Ph.D., D. Ross Camidge, M.D., Ph.D., Alice T. Shaw, M.D., Ph.D., et al, for the ALEX Trial Investigators- June 6, 2017DOI: 10.1056/NEJMoa1704795.

Comment: Alecensa currently holds a roughly 50% share of the second-line market, according to Roche, and the new trial results support expansion into first-line therapy.