Brigatinib Found More Effective for ALK-positive NSCLC Brain Mets Compared With Crizotinib

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Brigatinib significantly delayed time to intracranial progression and prolonged PFS compared with crizotinib in patients with ALK+ NSCLC with intracranial metastases.
Brigatinib significantly delayed time to intracranial progression and prolonged PFS compared with crizotinib in patients with ALK+ NSCLC with intracranial metastases.
The following article features coverage from the European Society for Medical Oncology (ESMO) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.

The next-generation ALK inhibitor brigatinib substantially delayed time to intracranial progression and prolonged interim progression-free survival (PFS) compared with crizotinib among patients with ALK-positive non-small cell lung cancer (NSCLC) with brain metastases, according to an analysis of the ALTA-1L trial presented at the ESMO 2018 Congress in Munich, Germany.1

Brigatinib met its primary end point in the phase 3 ALTA-1L trial of significantly prolonged PFS (hazard ratio [HR], 0.49; P = .0007) compared with crizotinib during its first interim analysis. This analysis evaluated outcomes of patients who had brain metastases at baseline.

In the phase 3 ALTA-1L trial, 275 patients with stage IIIB/IV ALK-positive NSCLC without prior tyrosine kinase inhibitor (TKI) treatment were randomly assigned to receive brigatinib or crizotinib. The primary end point was PFS — as assessed by a blinded independent review committee (BIRC) — and the secondary end points included intracranial objective response rate (iORR) and intracranial PFS (iPFS).

A brain metastasis of any kind was present at baseline in 33% of patients, and measurable brain metastases were present in 14% of participants. In the study, 14% of patients with any brain metastases received previous treatment with brain radiotherapy.

Brigatinib significantly prolonged iPFS in the intention-to-treat (ITT) and brain metastases cohorts compared with crizotinib. The median iPFS of the ITT population was not reached in both arms, with a 1-year rate of 78% (95% CI, 68%-85%) with brigatinib compared with 61% (95% CI, 50%-71%) with crizotinib (hazard ratio [HR], 0.42; 95% CI, 0.24-0.70; log-rank P = .0006).

Among patients with any baseline brain metastases, the median iPFS was 6 months (95% CI, 4-9 months) with crizotinib and not yet reached with brigatinib. The 1-year iPFS was 67% (95% CI, 47%-80%) with brigatinib compared with 21% (95% CI, 6%-42%) with crizotinib (HR, 0.27; 95% CI, 0.13-0.54; log-rank P < .0001).

Brigatinib significantly prolonged the time to intracranial progression without prior systemic progression by 70% compared with crizotinib in the ITT population (HR, 0.30; 95% CI, 0.15-0.60; P < .001), with a 1-year cumulative incidence of 12% (95% CI, 6%-20%) and 23% (95% CI, 15%-31%), respectively. The brigatinib arm also demonstrated a delayed tie to systemic progression without prior intracranial progression compared with crizotinib (HR, 0.51; 95% CI, 0.30-0.86; P = .017).

The confirmed iORR among patients with any brain metastases at baseline was 67% and 17% with brigatinib or crizotinib, respectively (Cochran-Mantel-Haenszel test P < .0001). The confirmed iORR was higher among patients with measurable brain disease, with a confirmed rate of 78% and 29% with brigatinib or crizotinib, respectively (Cochran-Mantel-Haenszel test P = .0028).

The authors concluded that these data suggest that “brigatinib has superior intracranial activity versus crizotinib in ALK TKI-naive patients with ALK-positive NSCLC.”

Disclosure: This study was funded by Millennium Pharmaceuticals, Inc.

Read more of Cancer Therapy Advisor's coverage of the ESMO 2018 meeting by visiting the conference page.

Reference

  1. Popat S, Janne PA, et al. Intracranial efficacy of brigatinib (BRG) vs crizotinib (CRZ) in the phase 3 ALTA-1L trial. Presented at: the ESMO 2018 Congress; Munich, Germany: October 19-23, 2018. Abstract LBA58.

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