Brigatinib in NSCLC Delays Progression; Survival Benefit Unclear

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Patients with ALK-positive advanced non-small cell lung cancer (NSCLC) who received brigatinib lived longer progression-free compared with patients who received crizotinib, showed a second prespecified interim analysis of the multicenter, randomized phase 3 ALTA-1L trial (ClinicalTrials.gov Identifier: NCT02737501).1

The first interim analysis, which had a median follow-up of 11 months for brigatinib, showed a significant progression-free survival (PFS) advantage for brigatinib compared with crizotinib, which was determined by a blinded independent review committee (BIRC; hazard ratio [HR], 0.49; 95% CI, 0.33–0.74; P <.001).2

The updated trial results were recently published in the Journal of Clinical Oncology.1

The trial enrolled 275 patients with ALK-positive disease who had not previously received an ALK-targeted therapy and randomly assigned 137 patients to receive brigatinib and 138 to receive crizotinib.

Having an additional 14 months of follow-up, the second interim analysis showed that at a median of 24.9 months follow-up, patients who received brigatinib continued to have a BIRC-assessed PFS advantage compared with patients who received crizotinib (HR, 0.49; 95% CI, 0.35–0.68; P <.0001), living a median of 13 months longer progression-free (24 vs 11 months).

This PFS benefit was seen across all patient subgroups, especially among patients who had brain metastases at baseline and a good Eastern Cooperative Oncology Group performance status.

Patients who received brigatinib also had a delayed worsening in global health status/quality-of-life score compared with patients who received crizotinib (26.7 vs 8.3 months; HR, 0.70; 95% CI, 0.49–1.00; P =.049).

In all, 73% of patients enrolled in the brigatinib arm experienced a grade 3 or higher adverse event compared with 61% of patients in the crizotinib arm.

An overall survival (OS) benefit for brigatinib was not seen compared with crizotinib (HR, 0.92; 95% CI, 0.57–1.47; P =.771). When adjusted for treatment crossover, OS was “in favor of” brigatinib (HR=0.70; 95% CI, 0.39 – 1.26), but this result was not statistically significant.

“The lack of OS benefit to date is likely due to the ALTA-1L protocol allowing patients in the crizotinib arm to switch to brigatinib after BIRC-confirmed progression,” the study authors asserted.

References

  1. Camidge DR, Kim HR, Ahn M, et al. Brigatinib versus crizotinib in advanced ALK inhibitor-naive ALK-positive non-small cell lung cancer: Second interim analysis of the phase III ALTA-1L trial. J Clin Oncol. Published online August 11, 2020. doi:10.1200/JCO.20.00505
  2. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK-positive non–small-cell lung cancer. N Engl J Med. 2018;379:2027-2039. doi:10.1056/NEJMoa1810171