Tony S.K. Mok, MD, FRCPC, FASCO, on Advanced ALK-Positive NSCLC: 7-Year Update From the CROWN Trial

At ASCO 2026, I have the pleasure of presenting the 7-year progression-free survival data from the CROWN study, which is a randomized phase 3 study of patients with advanced-stage ALK-positive non–small cell lung cancer randomized to receive either lorlatinib 100 mg daily or crizotinib 250 mg daily. Now, the primary endpoint is progression-free survival. The very first progression-free survival data were presented in 2020 in the New England Journal of Medicine, but at that time, the median progression-free survival had not been reached. Similarly, we looked at the data again and published them in JCO in 2024, and the median progression-free survival still had not been reached. Therefore, we have to look into the 7-year data. And now, after 83 months of follow-up, again, the median progression-free survival has not been reached. Then we learned a few things. Number 1 is the fact that at 84 months, the progression-free rate is 55%. So, in other words, over 50% of patients are still progression-free at the end of 7 years. Another point is the fact that between year 5 and year 7, there were only 7 progression events, 4 of which were related to disease progression. The other 3 were actually not related. One other important fact is that because of the 7-year follow-up, we can do the dynamics of the yearly progression-free rate. So, in the first 2 years, we had progression in about 30% of patients, but after that, every year is in the single digits. So between year 2, which is 70%, and year 5, which is 55%, that is only a 15% drop. But then we can kind of estimate that if the patient is progression-free at the second year, the chance of being progression-free at 7 years is actually very good, at 79%. So this is encouraging for the patient. And as for CNS control, 92% of patients actually had no CNS progression at the end of 7 years, which is phenomenal. So we also looked into the toxicity now that we have this hyperlipidemia, edema, neurotoxicity, and cognitive dysfunction. However, there was no significant difference between year 5 and year 7. The important aspect of this is that for patients who had high cholesterol, we were worried about cardiovascular events. But comparatively speaking, there was no difference in terms of cardiovascular events between the lorlatinib arm and the crizotinib arm. Patients did require dose reduction. Approximately 34% of patients required dose reduction. But then we also looked at the patients who had dose reduction within the first 26 weeks compared with patients who did not require dose reduction, and absolutely there was no difference in terms of progression-free survival, and there was no difference in terms of intracranial progression rate either. So overall, I think in conclusion, at 7 years of the CROWN study, we have not reached the median progression-free survival. Fifty-five percent of patients are still progression-free, and then there is a good chance the patient may have long-term survival in the future.