Pfizer (NYSE: PFE) reported seven-year follow-up data from the Phase III CROWN trial showing that 55% of previously untreated ALK-positive non-small cell lung cancer patients receiving lorlatinib (Lorbrena) remained alive without disease progression — a landmark in a disease where durable control at this timepoint has not previously been documented.
The CROWN trial is a randomized, open-label, Phase III study that enrolled 296 patients with previously untreated ALK-positive advanced or metastatic NSCLC, randomized 1:1 to lorlatinib (n=149) or Pfizer's Xalkori (crizotinib) (n=147). The seven-year analysis, an unplanned post-hoc assessment prompted by the fact that median progression-free survival remained unreached at both the three- and five-year marks, was based on investigator tumor assessment and presented at the 2026 ASCO Annual Meeting (Abstract #8502), with simultaneous publication in Annals of Oncology.
At seven years, the probability of remaining alive without progression was 55% (95% CI: 46–63) with lorlatinib versus 3% (95% CI: 1–8) with crizotinib. Investigator-assessed median PFS was not reached in the lorlatinib arm, with a hazard ratio of 0.19 (95% CI: 0.13–0.26), representing an 81% reduction in the risk of progression or death. The intracranial data were similarly striking: lorlatinib reduced the risk of intracranial progression by 94% (HR 0.06; 95% CI: 0.03–0.12), with no new intracranial progression events observed after the first 30 months. At the time of analysis, 44% of patients in the lorlatinib arm remained on treatment, compared with 3% in the crizotinib arm. The safety profile was consistent with prior analyses. Grade 3/4 adverse events occurred in 77% of lorlatinib patients versus 57% with crizotinib, though treatment-related discontinuations were low and comparable — 5% versus 6%, respectively — with no new permanent discontinuations due to treatment-related adverse events after the first 26 months on lorlatinib.
Competitive context
Lorlatinib is a third-generation ALK/ROS1 tyrosine kinase inhibitor engineered specifically to overcome resistance mutations that limit earlier-generation agents and to penetrate the blood-brain barrier — properties that appear central to the durability seen in CROWN. The first-line ALK-positive NSCLC space now includes several approved oral agents: Roche's Alecensa (alectinib), Takeda's Alunbrig (brigatinib), Novartis's Zykadia (ceritinib), and, most recently, Xcovery's Ensacove (ensartinib), approved in December 2024. Cross-trial comparisons are limited by differences in patient populations, follow-up duration, and analytical methods, but no other agent in this class has reported a median PFS that remains unreached at seven years. Overall survival data from CROWN remain immature, and those results will be the next material readout for the program.
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