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News|Articles|October 24, 2026 Baseline and on-treatment circulating tumor DNA (ctDNA) features, including TP53 mutations and methylation-based tumor fraction, were associated with early progression or prolonged progression-free survival (PFS) with first-line lorlatinib (Lorbrena) in patients with ALK-positive advanced non–small cell lung cancer (NSCLC), in exploratory analyses of the phase 3 CROWN trial (NCT03052608) presented at the 2026 European Society for Medical Oncology (ESMO) Congress.1Compared with long-term responders, who were progression free at 84 months (n = 30), early progressors, who had a PFS event within 12 months (n = 22), had a higher median number of altered genes at baseline (10 vs 6), a higher median blood-based tumor mutation burden (7.7 vs 5.1), and more frequent TP53 mutations (50% vs 17%). In the lorlatinib arm, the 7-year PFS rate was 65.0% (95% CI, 54.5%-77.4%) in patients with TP53 wild-type disease (n = 73) vs 40.8% (95% CI, 27.3%-61.1%) in those with TP53-mutated disease (n = 43; HR, 0.48; 95% CI, 0.268-0.857); median PFS was not reached (NR) vs 51.6 months (95% CI, 16.4-NR), respectively.

CML treatment has transformed long-term survival, allowing many patients receiving effective TKI therapy to achieve a life expectancy approaching that of the general population. Molecular response milestones guide personalized treatment decisions, helping clinicians assess treatment effectiveness, recognize inadequate responses, and adjust therapy when necessary.