Lorbrena shows persistent PFS benefit at 7 years in ALK+ NSCLC | ASCO 2026

Seven-year follow-up data from the phase 3 CROWN trial show persistent benefits with Lorbrena (lorlatinib) as a first-line treatment for patients with advanced ALK-positive non-small cell lung cancer (NSCLC), with median progression-free survival (PFS) still not reached at the time of the analysis.

The 7-year findings, which are being presented by lead author Tony S.K. Mok, M.D., FRCPC, FASCO, at the 2026 American Society of Clinical Oncology Annual Meeting in Chicago, represent the longest PFS ever reported in advanced NSCLC. These data build upon promising 5-year results, reinforcing Lorbrena’s position as a frontline standard of care for ALK-positive disease. Lorbrena received full FDA approval as a frontline treatment for ALK-positive NSCLC in 2021, based on earlier CROWN interim data.

As of October 31, 2025, 44% of patients in the Lorbrena arm remained on treatment compared with 3% of those who received Xalkori (crizotinib). At a median follow-up of 83 months for Lorbrena and 77.2 months for Xalkori, median PFS was not reached in the Lorbrena arm versus 9.1 months with Xalkori.

The 7-year PFS rate was 55% with Lorbrena versus 3% with Xalkori. Notably, patients who had not experienced a PFS event by the end of 24 months had a 79% probability of remaining progression-free at year seven, and the PFS benefit was consistent across all prespecified patient subgroups.

Lorbrena's intracranial efficacy was persistent at 7 years. No new intracranial progression events occurred after the first 30 months on Lorbrena, and median time to intracranial progression was not reached in the Lorbrena arm versus 16.4 months with Xalkori — translating to a 94% reduction in intracranial progression risk. Given that 25% to 45% of patients with ALK-positive NSCLC could develop brain metastases by two years after diagnosis, persistent central nervous system control is clinically meaningful in this population.

“These seven-year outcomes from the CROWN study are remarkable not only for their durability of tumor response but also for what they represent — a fundamental shift in what clinicians and patients might reasonably expect from treatment for advanced-stage NSCLC,” Mok said in a statement. “Observing this level of long-term benefit with a once-daily oral therapy, both in terms of sustained progression-free survival and prevention of brain metastases, would have been difficult to imagine when we first developed ALK-specific targeted therapy a decade ago and underscores the significance of these results for the lung cancer community.”

Lorbrena’s safety profile was consistent with the 5-year analysis. Grade 3 or 4 adverse events occurred in 77% of Lorbrena patients and 57% of Xalkori patients. Treatment-related adverse events led to permanent discontinuation in 5% of Lorbrena patients and 6% of Xalkori patients, with no new permanent discontinuations due to treatment-related adverse events after the first 26 months.

Dose reductions were reported in 34% of patients in the Lorbrena arm — 17% had one reduction and 17% had two — but long-term efficacy was similar regardless of dose modification, consistent with prior post hoc analyses showing dose reductions are effective for managing toxicity without compromising outcomes.

The CROWN trial randomized 296 treatment-naive patients with advanced ALK-positive NSCLC 1:1 to Lorbrena at a dosage of 100 mg once daily or Xalkori at 250 mg twice daily. The 7-year analysis was a post hoc assessment; formal statistical testing between arms was not performed. The number of overall survival events required for a protocol-specified analysis has not yet been met, and overall survival follow-up is ongoing.

"With median PFS yet to be reached after 7 years of follow-up in CROWN, lorlatinib continues to show unprecedented and highly durable benefit in treatment-naive patients with advanced ALK+ NSCLC," Mok and colleagues wrote in their conclusions.