Roche has announced that the European Commission (EC) has granted a marketing authorisation for Alecensa (alectinib) as a monotherapy for the first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive, advanced non-small cell lung cancer (NSCLC). The approval is based on results from the phase III ALEX study, which showed Alecensa significantly reduced the risk of disease worsening or death (progression-free survival, PFS) by 53% (hazard ratio (HR)=0.47, 95% confidence interval (CI): 0.34-0.65, p<0.001) compared to crizotinib. The study also showed that Alecensa reduced the risk of tumours spreading to, or growing in the brain or central nervous system (CNS) compared to crizotinib by 84% (HR=0.16, 95% CI: 0.10-0.28, p<0.001). The safety profile of Alecensa was consistent with that observed in previous studies and compared favourably to crizotinib.
“Many ALK-positive lung cancer patients see their disease progress within a year on current treatments,” said Sandra Horning, MD, Roche’s chief medical officer and head of global product development. “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.”
In addition to the first-line approval, the EC also converted the conditional marketing authorisation of Alecensa in crizotinib failure to a standard marketing authorisation. Alecensa has also recently (6 November 2017) been approved by the US FDA, as well as Japan and Turkey as an initial (first-line) ALK-positive NSCLC treatment, and is already approved in Japan as well as in 18 countries in the crizotinib-failure setting.
Results from the phase III ALEX study were simultaneously presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine. Subsequently, Alecensa was recommended in the US National Comprehensive Cancer Network (NCCN) guidelines as a treatment option for first-line ALK-positive metastatic NSCLC (Category 1, Preferred).
ALK-positive NSCLC is a distinct form of lung cancer commonly affecting younger people (median age 52), and those with a light or non-smoking history.3 Around 75,000 people are diagnosed with ALK-positive NSCLC every year.
ALEX (NCT02075840/B028984) is a randomised, multicentre, open-label phase III study evaluating the efficacy and safety of Alecensa versus crizotinib in treatment-naïve people with ALK-positive NSCLC whose tumours were characterised as ALK-positive by the VENTANA ALK (D5F3) CDx Assay, a companion immunohistochemistry (IHC) test developed by Roche Tissue Diagnostics. People were randomised (1:1) to receive either Alecensa or crizotinib. The primary endpoint of the ALEX study is PFS as assessed by the investigator, and secondary endpoints include: Independent Review Committee (IRC)-assessed PFS, time to CNS progression, objective response rate (as defined by RECIST criteria), duration of response, overall survival, health-related quality of life and safety. The multicentre study was conducted in 303 people across 161 sites in 31 countries. 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 with the crizotinib arm (50%). In the Alecensa arm, the most common AEs (=10% absolute difference) were (Alecensa versus crizotinib): increased blood bilirubin (15% versus 1%) increased weight (10% versus 0%), decreased red blood cells (anaemia; 20% versus 5%) and myalgia (16% versus 2%). AEs leading to discontinuation (11% versus 13%), dose reduction (16% versus 21%) and dose interruption (19% versus 25%) were all lower in the Alecensa arm compared with the crizotinib arm.