Roche has announced that the phase III ALEX study showed Alecensa (alectinib) significantly reduced the risk of disease worsening or death (progression-free survival, PFS) by more than half (53%) compared to crizotinib 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.
“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.”
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.
The official ALEX data was presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting. The data will be simultaneously published in the New England Journal of Medicine, and has officical features at ASCO press programme.
Data from the ALEX study will be submitted to global health authorities, including the US Food and Drug Administration (FDA), which in September 2016 granted Alecensa Breakthrough Therapy Designation (BTD) for the treatment of people with advanced ALK-positive NSCLC who have not received prior treatment with an ALK inhibitor.
Alecensa is approved as a monotherapy for people with ALK-positive NSCLC who have progressed on or are intolerant to crizotinib in Europe, the US and ten other countries globally. Alecensa is also approved in Japan for people whose tumours were advanced, recurrent or could not be removed completely through surgery (unresectable). In the US, Alecensa 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. The ALEX study is part of the company’s commitment in the US to convert the current accelerated approval of Alecensa in people with ALK-positive, metastatic NSCLC who have progressed on or are intolerant to crizotinib to a full approval as an initial treatment.
In the European Union, Alecensa was granted conditional marketing authorisation in February 2017 as monotherapy for people with ALK-positive advanced NSCLC previously treated with crizotinib. Under the provisions of the conditional EU approval, Roche is submitting the ALEX study as the specific obligation to obtain full approval of Alecensa as an initial treatment for ALK-positive advanced NSCLC.