medwireNews: The eXalt3 study has shown significantly better progression-free survival (PFS) with ensartinib versus crizotinib in ALK inhibitor-naïve patients with ALK alteration-positive, advanced non-small-cell lung cancer (NSCLC).
These phase 3 results were presented at the IASLC’s World Conference on Lung Cancer Virtual Presidential Symposium 2020 by Leora Horn, from the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, USA.
She noted that ensartinib improved outcomes in patients with and without brain metastases at baseline, and added that the agent had “a favorable safety profile.”
Horn therefore believes this next-generation ALK inhibitor “represents a new first-line treatment option for patients with ALK-positive non-small-cell lung cancer.”
She reported on a preplanned interim analysis of the intention-to-treat (ITT) population that included 290 participants with locally confirmed ALK-positive, stage IIIB or IV disease who had not previously received an ALK inhibitor and had received no more than one prior chemotherapy regimen. Horn also presented data on the modified ITT cohort comprising 247 patients deemed ALK-positive by central review.
PFS, as assessed by blinded independent review, was significantly prolonged for the patients who were randomly assigned to receive ensartinib 225 mg/day compared with those given crizotinib 250 mg twice daily in the ITT and modified ITT populations, at a median of 25.8 versus 12.7 months and unreached versus 12.7 months, respectively. The corresponding hazard ratios (HRs) for progression or death were 0.51 and 0.45.
The objective response rate (ORR) was higher with ensartinib than crizotinib, at 75% versus 67%, the proportion of complete responses was more than double, at 14% versus 6%, and the median duration of response was longer, at unreached versus 27.3 months.
The overall survival data were not mature at the time of analysis as only around 20% of events had occurred in both the ensartinib and crizotinib arms, said the presenter.
Ensartinib appeared to be beneficial relative to crizotinib regardless of baseline brain metastases. For instance, the intracranial ORR was 64% with ensartinib and 21% with crizotinib among the 30 patients with measurable brain metastases. And among the 157 participants without brain metastases, median PFS was unreached and 16.6 months with ensartinib and crizotinib, respectively, a significant difference (HR=0.40).
The most common treatment-related adverse events (TRAEs) with ensartinib were rash and transaminitis, but these tended to be of low grade, Horn reported.
Patients given ensartinib had higher rates of serious TRAEs than their crizotinib-treated counterparts (8 vs 6%), and were also more likely to require a dose reduction (24 vs 20%) or to discontinue treatment (9 vs 7%).
Christine Lovly, also from the Vanderbilt Ingram Cancer Center, said in her discussion of the presentation that although multiple options are currently available for first-line ALK inhibitor therapy, there is a need to “move the needle” to further improve treatment paradigms for patients.
She outlined several options to explore in future research, such as combinations in the first- and later-line, consideration of co-mutations, alternative approaches to targeting ALK (eg, allosteric inhibitors, vaccines), and adjuvant use of ALK inhibitors.
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