CHICAGO – In what’s being hailed as practice-changing findings, the anaplastic lymphoma kinase inhibitor alectinib (Alecensa) was associated with more than doubled progression-free survival (PFS), compared with crizotinib (Xalkori), the current standard of care, in patients with treatment-naive non–small cell lung cancer (NSCLC) positive for ALK.
Additionally, in the global, phase III trial, alectinib was associated with a significantly lower risk of progression to CNS metastases, a common complication of advanced ALK+ NSCLC, reported Alice T. Shaw, MD, PhD, of the Massachusetts General Hospital Cancer Center in Boston, on behalf of investigators in the ALEX trial.
Neil Osterweil/Frontline Medical news
Dr. Alice T. Shaw
“I view this as a watershed moment for the treatment of ALK mutant–positive lung cancer,” commented ASCO expert John Heymach, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston.
Unlike other head-to-head studies of similar drugs that frequently show only incremental benefit, the ALEX results showed a dramatic difference in outcomes for patients treated with alectinib, he said.
By comparison, the median PFS difference between chemotherapy and crizotinib in the PROFILE 1014 in patients with ALK-positive NSCLC trial was 10.9 vs. 7.0 months, Dr. Heymach pointed out.
The ALEX investigators enrolled 303 patients with untreated ALK-positive NSCLC confirmed by a central immunohistochemistry lab and randomly assigned them to treatment with either oral alectinib 600 mg twice daily or crizotinib 250 mg b.i.d.
At the primary data cutoff in February 2017, median PFS, the primary endpoint, was 11.1 months for patients treated with crizotinib, versus not reached for those treated with alectinib, translating into a hazard ratio for alectinib of 0.47 (P less than .0001).
Based on an independent review, the median PFS was determined to be 10.4 months for crizotinib, vs. 25.7 months with alectinib (HR, 0.50; P not shown).
The cumulative incidence of CNS progression, a secondary endpoint, was 41.4% in the crizotinib arm, vs. 9.41% in the alectinib arm (cause-specific HR, 0.16; P not shown).
In each arm, 97% of patients had any adverse event, and the incidence of serious adverse events was similar between the arms, at 29% for crizotinib and 28% for alectinib.
Adverse events leading to treatment discontinuation, dose reduction, or dose interruption were more frequent with crizotinib.
In the question and answer portion of the briefing, Dr. Shaw was asked whether crizotinib still had a role in this population.
“Going forward, I think that it’s pretty clear, if you have a newly diagnosed patient with metastatic ALK-positive lung cancer, that likely alectinib would be the preferred first choice,” she said.
The ALEX trial is supported by Roche. Dr. Shaw disclosed consulting or an advisory role with the company, and multiple coauthors disclosed similar relationships.