FDA Grants Breakthrough Therapy Designation for First-Line Treatment of ALK-Positive NSCLC
On October 4, 2016, the U.S. Food and Drug Administration (FDA) granted alectinib (Alecesna), an anaplastic lymphoma kinase (ALK) inhibitor, a second Breakthrough Therapy designation. This latest designation was granted for the treatment of adult patients with advanced ALK-positive non–small cell lung cancer (NSCLC) who have not received prior treatment with an ALK inhibitor, based on results of the J-ALEX trial.
“The J-ALEX study that supports the second Breakthrough Designation for alectinib showed superior efficacy vs the standard of care, crizotinib [Xalkori], in Japanese [patients] with advanced ALK-positive disease,” said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development at Genentech. “The decision by the FDA to grant a second Breakthrough Therapy designation is recognition of the clinically meaningful improvement in efficacy and safety that alectinib brings to the care of people with advanced ALK-positive lung cancer who have not received prior treatment with an ALK inhibitor.”
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. Alectinib received its first FDA Breakthrough Therapy designation in June 2013 for patients with ALK-positive NSCLC whose disease progressed on treatment with crizotinib.
Alectinib was granted accelerated approval by the FDA in December 2015 for the treatment of people with ALK-positive NSCLC who have progressed on or are intolerant to crizotinib. ALEX, an ongoing global, randomized phase III study is comparing alectinib to crizotinib as a first-line treatment for people with advanced NSCLC whose tumors were characterized as ALK-positive by a companion VENTANA ALK (D5F3) CDx Assay immunohistochemistry test developed by Roche Tissue Diagnostics.
About J-ALEX
The J-ALEX study, conducted by Chugai, is an open-label, randomized phase III study that compared the efficacy and safety of alectinib to crizotinib in Japanese patients. J-ALEX enrolled 207 people with ALK-positive advanced or recurrent NSCLC who had not been previously treated with an ALK inhibitor. People were randomized to the alectinib group or the crizotinib group in a 1:1 ratio. Results included:
- Alectinib reduced the risk of disease progression or death by 66% compared to crizotinib (hazard ratio [HR] = 0.34, 99% confidence interval [CI] = 0.17–0.70, P < .0001).
- Median progression-free survival was not reached in the alectinib arm (95% CI = 20.3 months to not estimated) vs 10.2 months in the crizotinib arm (95% CI = 8.2–12.0).
- Grade 3-4 adverse events occurred with greater frequency in the crizotinib arm compared to the alectinib arm (27% vs 51%).
The most common adverse events occurring with > 30% frequency with alectinib was constipation (36%). The most common adverse events for crizotinib were nausea (74%), diarrhea (73%), vomiting (59%), visual disturbance (55%), dysgeusia (52%), constipation (46%), and an elevation in liver enzymes alanine transaminase (32%) and aspartate transaminase (31%).
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
