Alectinib ( Alecensa ), an oral anaplastic lymphoma kinase ( ALK ) inhibitor, has reduced the risk of disease worsening or death ( progression free survival, PFS ) by 66% compared to Crizotinib ( Xalkori ) in Japanese people with advanced or recurrent, ALK-positive non-small cell lung cancer ( NSCLC ) ( hazard ratio, HR=0.34, 99% CI: 0.17-0.70, p less than 0.0001 ).
Median PFS was not reached in people who received Alectinib ( 95% CI: 20.3 months-not reached ) versus 10.2 months median PFS ( 95% CI: 8.2-12.0 ) in people who received Crizotinib.
The results were from a pre-specified interim analysis from the phase III J-ALEX study in people who had not received prior treatment with an ALK-inhibitor.
There were fewer adverse events in the Alectinib arm versus the Crizotinib arm. Alectinib has demonstrated a safety profile consistent with that observed in previous studies with no new or unexpected adverse effects.
Alecensa was granted accelerated approval by the FDA ( Food and Drug Administration ) in December 2015 for the treatment of people with ALK-positive NSCLC who have progressed on or are intolerant to Crizotinib.
ALEX, a global, randomised phase III study, is ongoing, comparing Alectinib to Crizotinib as a first-line treatment for people with advanced NSCLC whose tumours were characterised as ALKpositive by a companion VENTANA ALK (D5F3) CDx Assay immunohistochemistry ( IHC ) test developed by Roche Tissue Diagnostics.
The J-ALEX study is an open-label, randomised phase III study that compared the efficacy and safety of Alectinib to Crizotinib in Japanese people. The J-ALEX study enrolled 207 people with ALK-positive, advanced or recurrent NSCLC who had not been previously treated with an ALK-inhibitor.
People were randomised to the Alectinib group or the Crizotinib group in a one-to-one ratio. Results include:
Alectinib has reduced the risk of disease worsening or death ( PFS ) by 66% compared to Crizotinib ( HR=0.34, 99% CI: 0.17-0.70, p less than 0.0001 ).
Median progression-free sirvival was not reached in the Alectinib arm ( 95% CI: 20.3 months-not estimated ) versus 10.2 months in the Crizotinib arm ( 95% CI: 8.2-12.0 ).
Grade 3-4 adverse effects occurred with greater frequency in the crizotinib arm compared to the Alectinib arm ( 51% versus 27% ).
The most common adverse effect occurring with more than 30% frequency with Alectinib was constipation ( 36% ). The most common adverse effects for Crizotinib were nausea ( 74% ), diarrhoea ( 73% ), vomiting ( 59% ), visual disturbance ( 55% ), alteration in taste ( dysgeusia; 52% ), constipation ( 46% ), and an elevation in liver enzymes called alanine transaminase ( ALT, 32% ) and aspartate transaminase ( AST, 31% ).
Alectinib is an oral medicine created at Chugai Kamakura Research Laboratories and is being developed for people with NSCLC whose tumours are identified as ALK+.
ALK+ NSCLC is often found in younger people who have a light or non-smoking history. It is almost always found in people with a specific type of NSCLC called adenocarcinoma.
Alecensa is currently approved in the United States for the treatment of advanced ( metastatic ) ALK-positive NSCLC whose disease has worsened after, or who could not tolerate treatment with, Crizotinib.
In two key phase II studies, NP28761 and NP28673, Alectinib shrank tumours in up to 44% of people with ALK-positive NSCLC who progressed on Crizotinib.
Alectinib also demonstrated activity in brain metastases, indicating that the drug may be taken up in the brain. The brain is protected by the blood-brain barrier, a network of tightly joined cells that line the inside of the blood vessels in the brain and spinal cord.
One of the ways the blood-brain barrier prevents molecules from affecting the brain is to actively eject them from the barrier through a process known as active efflux. The active efflux system does not recognise Alectinib, which means that it may travel into and throughout brain tissue. ( Xagena )
Source: Roche, 2016