Roche Receives FDA Approval for Alecensa

By Michael Vlessides, Contributor
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The treatment landscape for patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) has changed significantly in recent weeks with the U.S. Food and Drug Administration’s (FDA) approval of Alecensa (alectinib), a highly selective ALK inhibitor.

The approval is based largely on results from the phase III ALEX trial, which revealed that the novel agent not only reduced the risk of disease worsening or death by 47% compared with crizotinib, but it also improved median progression-free survival to 25.7 months, compared with 10.4 months for those taking crizotinib.

The FDA approval comes less than two years after the agency granted accelerated approval to alectinib in December 2015 for the treatment of patients with ALK-positive metastatic NSCLC whose disease had progressed on or who were intolerant of crizotinib.

Alectinib. (Source: Japan Science and Technology Agency)

As part of ALEX trial -- an open-label, randomized controlled study conducted in 161 sites across 31 countries -- alectinib was compared with crizotinib in 303 patients with ALK-positive NSCLC who had not received prior systemic therapy for metastatic disease and whose tumors were characterized as ALK-positive by an FDA-approved test. Participants were randomized to receive twice-daily does of either 600mg alectinib (n=152) or 250mg crizotinib (n=151). The study’s primary endpoint was investigator-assessed progression-free survival; secondary endpoints included time to central nervous system (CNS) progression, objective response rate, and overall survival.

It was found that over a median follow-up of 17.6 months for crizotinib and 18.6 months for alectinib, an event of disease progression or death occurred in 62 of 152 patients (41%) in the alectinib group, compared with 102 of 151 crizotinib patients (68%). Moreover, the rate of investigator-assessed progression-free survival was significantly higher with alectinib (12-month event-free survival rate 68.4%; 95% CI 61.0-75.9) than with its counterpart (48.7%; 95% CI 40.4-56.9). In total, a response occurred in 126 alectinib patients (82.9% response rate; 95% CI 76.0-88.5) and 114 crizotinib patients (75.5% response rate; 95% CI 67.8-82.1; p=0.09).

Alectinib was also shown to significantly reduce the risk of the cancer spreading t, or growing in the brain or central nervous system (CNS) by 84% (HR=0.16, 95% CI 0.10-0.28; p<0.0001) relative to crizotinib. This was based on a time-to-CNS progression analysis, which yielded a lower risk of progression in the CNS as the first site of disease progression for alectinib patients (n=18; 12%) than with crizotinib patients (n=68; 45%).

Alectinib’s safety profile was consistent with that observed in previous studies. The most common alectinib-related grade 3-4 adverse reactions (≥3%) included increased creatinine (4.1%), hyperbilirubinemia (5%), hyponatremia (6%), increased liver enzymes (aspartate transaminase 6%; alanine transaminase 6%), and anemia (7%). Serious adverse reactions reported in ≥2% of patients treated with alectinib were lung infection (pneumonia; 4.6%) and renal impairment (3.9%). Grade 3-5 adverse events were less frequent with alectinib (41%) than crizotinib (50%).

Positive reaction to the drug’s approval was swift. The National Comprehensive Cancer Network recommended alectinib as a category 1 preferred treatment option for first-line ALK-positive metastatic NSCLC (NCCN Guidelines. Non-small cell lung cancer. Version 7. 2017.)

Alectinib is currently approved in the United States, Europe, Kuwait, Israel, Hong Kong, Canada, South Korea, Switzerland, India, Australia, Singapore, Taiwan, Liechtenstein, Thailand, United Arab Emirates, Saudi Arabia, Argentina, and Turkey for the treatment of patients with metastatic ALK-positive NSCLC whose disease has worsened after, or who could not tolerate treatment with, crizotinib. The drug is approved for use in Japan for people with ALK-positive NSCLC.

In conjunction with its approval of alectinib, the FDA also approved the Ventana ALK CDx Assay as a companion diagnostic to identify ALK-positive non-small cell lung cancer patients eligible for treatment with alectinib. The assay is the only test approved by the FDA as a companion diagnostic for alectinib, according to both Roche and the FDA.