FDA has granted Breakthrough Therapy Designation for Alecensa for first-line treatment of people with ALK-positive non-small cell lung cancer
Alecensa ( Alectinib ), an ALK inhibitor, has received a second Breakthrough Therapy Designation ( BTD ) from the United States Food and Drug Administration ( FDA ). The latest BTD was granted for the treatment of adult patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer ( NSCLC ) who have not received prior treatment with an ALK inhibitor.
This second breakthrough therapy designation is based on the results of the open-label, randomised phase III J-ALEX study, which were presented at the American Society of Clinical Oncology ( ASCO ) 2016 Annual Meeting.
J-ALEX compared the efficacy and safety of Alectinib with Crizotinib ( Xalkori ) in 207 Japanese people with ALK-positive, advanced or recurrent NSCLC who either had not been treated with chemotherapy or had received one prior line of chemotherapy.
Results from the study have demonstrated that Alectinib reduced the risk of disease worsening or death ( progression-free survival, PFS ) by 66% compared to Crizotinib, whilst maintaining a favourable tolerability and safety profile consistent with that observed in previous studies.
The FDA’s Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious diseases and to help ensure patients have access to them through FDA approval as soon as possible.
Alecensa received its first FDA BTD in June 2013 for people with ALK-positive NSCLC whose disease progressed on treatment with Crizotinib.
In the J-ALEX study patients were randomised to the Alectinib group or the Crizotinib group in a one-to-one ratio.
Alectinib has reduced the risk of disease worsening or death by 66% compared to Crizotinib ( HR=0.34, 99% CI: 0.17-0.70, p less than 0.0001 ).
Median PFS 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 events occurred with lesser frequency in the Alectinib arm compared to the Crizotinib arm ( 27% vs 51% ).
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% ).
Lung cancer is the biggest cancer killer, causing 1.59 million deaths globally each year. NSCLC is the most common type of lung cancer, and is the leading cause of cancer-related deaths in Europe and across the world, accounting for approximately 85% of lung cancer cases.
ALK-positive NSCLC occurs in approximately 5% of patients with advanced NSCLC, translating to about 75,000 patients being diagnosed with the disease annually. It is almost always found in people with a specific type of NSCLC called adenocarcinoma, and is more common in light or non-smokers. ( Xagena )
Source: Roche, 2016