medwireNews: Among Japanese patients with advanced non-small-cell lung cancer (NSCLC) harboring anaplastic lymphoma kinase (ALK) translocations, progression-free survival (PFS) is significantly longer with alectinib than crizotinib, shows a head-to-head phase III trial.
The second-generation ALK inhibitor also appeared to be better tolerated than crizotinib, the current standard of care, in this population of patients who were either chemotherapy-naïve or had received only one prior chemotherapy regimen.
These findings “have the potential to change the standard of care for the first-line treatment of ALK-positive non-small-cell lung cancer,” say Tomohide Tamura, from St Luke’s International Hospital in Tokyo, Japan, and fellow J-ALEX collaborators.
They continue: “The characteristics of alectinib, including its potent ALK inhibitory activity, high selectivity, activity against ALK secondary mutations that are resistant to crizotinib, and [central nervous system] penetration, might contribute to the significant result obtained in this study.”
After a median follow-up of 12.0–12.2 months, median PFS by independent review was not reached for the 103 patients with stage IIIB–IV or postoperative recurrent disease who were randomly assigned to receive open-label alectinib 300 mg twice daily and was 10.2 months for the 104 given crizotinib 250 mg twice daily. This equated to a significant hazard ratio (HR) of 0.34 favoring alectinib.
Tamura et al report in The Lancet that the HR remained unchanged in a multivariate analysis accounting for “the potential effect of imbalance in the distribution of prognostic factors between treatment groups,” on the primary result, such as brain metastases, observed in a respective 14% and 28% of alectinib- and crizotinib-treated patients.
The objective response rate, as assessed by independent review, was also higher in the alectinib than the crizotinib treatment arm, at 92% and 79%, respectively. And alectinib treatment significantly reduced the risk for progression of brain metastatic lesions or death in patients with brain metastases at baseline (HR=0.16) and the risk for metastasis to the brain or death in those free of intracranial lesions at baseline (HR=0.41).
Toxicities of grade 3 or 4 were less frequent in the alectinib than the crizotinib group, experienced by 26% and 52% of participants, respectively, as were adverse event-related dose interruptions and discontinuations, at 29% versus 74% , and 9% versus 20%, respectively.
There were no deaths attributable to adverse events in either treatment arm.
Justin Gainor and Alice Shaw (both from Massachusetts General Hospital, Boston, USA) say in a related comment that the J-ALEX results “are impressive and are a major step forward in the treatment of non-small-cell lung cancer.”
But they believe that certain questions remain answered. For instance, the J-ALEX participants received alectinib at a lower dose than that used outside of Japan (600 mg twice daily), leading the commentators to wonder if these findings are “generalisable to non-Japanese patient populations.”
They, and the study authors, await the results of the ongoing global ALEX trial, which should clarify the generalizability issue.
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