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26-05-2017 | Non-small-cell lung cancer | News | Article

Alectinib outperforms crizotinib in Japanese patients with ALK-rearranged NSCLC

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.

By Shreeya Nanda

medwireNews is an independent medical news service provided by Springer Healthcare. © 2017 Springer Healthcare part of the Springer Nature group

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