Alectinib ‘new standard of care’ for untreated ALK-positive NSCLC
medwireNews: Compared with crizotinib, alectinib significantly improves progression-free survival (PFS) in treatment-naïve patients with advanced non-small-cell lung cancer (NSCLC) harboring an anaplastic lymphoma kinase (ALK) rearrangement, shows the ALEX trial.
The next-generation ALK inhibitor also compared favorably against the standard of care crizotinib in terms of controlling and preventing central nervous system (CNS) metastases, and was better tolerated, Alice Shaw, from Massachusetts General Hospital in Boston, USA, said at the 2017 annual meeting of the American Society of Clinical Oncology in Chicago, Illinois, USA.
She added that their results, simultaneously published in The New England Journal of Medicine, are consistent with studies of alectinib in Japanese populations, such as the J-ALEX trial, which also showed significantly improved outcomes with alectinib over crizotinib.
In the phase III ALEX trial, 152 NSCLC patients with stage IIIB or IV, ALK-positive disease were randomly assigned to receive first-line alectinib 600 mg twice a day, while their 151 counterparts received crizotinib 250 mg twice daily. Approximately 40% of patients in each group presented with CNS metastases at baseline and just over half were of non-Asian ethnicity.
After a median 17.6 months, the primary endpoint of investigator-assessed PFS was longer for alectinib than crizotinib-treated patients, with the median not reached and 11.1 months, respectively, and a significant hazard ratio (HR) of 0.47.
The findings were similar when PFS was evaluated by an independent review committee, at a median of 25.7 months for the alectinib group versus 10.4 months for the crizotinib group and an HR of 0.50.
Competing risks analysis showed that alectinib therapy prolonged the time to CNS progression as the first event by a significant 84% relative to crizotinib and reduced the cumulative incidence of CNS progression, at 12-month rates of 9.4% and 41.4%, respectively.
Alectinib also elicited an intracranial response – of 43 patients with measurable disease at intake, 81% of those given alectinib responded compared with 50% of those who received crizotinib, with complete responses in 38% and 5%, respectively. The median duration of response was also longer with alectinib than crizotinib, at 17.3 versus 5.5 months.
The HR for disease progression or death was 0.40 in favor of alectinib for the subgroup with CNS lesions at baseline and 0.51 for those without, showing that both sets of patients derived benefit from the next-generation inhibitor, Shaw told the attendees.
Alectinib also appeared to have a more favorable safety profile, with fewer patients experiencing grade 3–5 adverse events than their crizotinib-treated counterparts (41 vs 50%) and lower rates of dose reductions (16 vs 21%), dose interruptions (19 vs 25%), and treatment discontinuation (11 vs 13%) attributable to toxicity. However, the rates of serious adverse events were comparable (28 vs 29%).
The presenter concluded that “these results establish alectinib as the new standard of care” for the first-line treatment of patients with advanced ALK-positive NSCLC.
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