Seven years after the CROWN trial began, updated results show that the ALK inhibitor lorlatinib continues to deliver what researchers describe as the longest progression-free survival ever reported for any lung cancer therapy — and possibly for any solid tumor. The findings, presented in a recent discussion by Drs. Christine Lovly and Alice Shaw, reinforce a growing consensus that lorlatinib may deserve a preferred position in treatment guidelines for ALK-positive non-small cell lung cancer.
Unprecedented survival and brain metastasis prevention
Dr. Shaw distilled three key takeaways from the seven-year update. The first is the sheer magnitude of the progression-free survival benefit.
The second finding centers on the drug’s activity in the central nervous system. Over that follow-up period, 92% of patients remained free of intracranial progression. That means lorlatinib not only treats existing brain metastases but also prevents them from developing in the first place — a clinically important outcome given how often ALK-positive patients develop CNS disease.
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Dr. Shaw emphasized that proactive safety management must continue for the full duration of therapy, not just in the early months.
What the data still doesn’t show
The study has limitations.
She acknowledged that biomarker analyses aimed at identifying which patients are likely to progress early versus those who will enjoy durable responses remain preliminary. And the overall survival data, while highly anticipated, are not yet mature enough to report.
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She expressed confidence that survival numbers will ultimately prove equally impressive, but for now the field must wait.
That wait leaves a gap. Without mature overall survival results, some payers and guideline committees may hesitate to shift treatment hierarchies. Yet the progression-free survival and CNS data are so stark that clinical practice may move ahead of the formal evidence — a pattern seen before in oncology when a therapy’s effect is large enough to make the missing endpoint feel almost academic.
Guideline implications and a shift in preference
Current NCCN guidelines list second- and third-generation ALK inhibitors as co-equal preferred options. Dr. Shaw was asked whether the seven-year update changes how doctors currently treat the disease or simply reinforces existing practice. Her answer was direct: the magnitude of the CROWN data compels her to rank lorlatinib above the others.
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That view is not yet reflected in the official guidelines, but it signals where expert opinion is headed.
The discussion closed with two calls to action from Dr. Lovly. She reminded clinicians that biomarker testing remains the essential gateway to delivering these therapies. Without testing, patients cannot access targeted treatments. She also introduced the ALK Positive patient advocacy community as a vital resource for patients and families dealing with this diagnosis.
