Not mentioned in the article is the fact that lorlatinib, original studied in the phase 3 CROWN trial, was used in frontline management of advanced ALK-mutated non-small cell lung cancer (NSCLC) [0]. Five-year data indicate a significant progression-free survival benefit, with 60% of patients free of progression. Even after 60.2 months of follow-up, the median progression-free survival has not yet been reached [1]. It is the durability of progression-free survival that are most impressive and surprising here. That said, only 4% to 8% of patients with NSCLC will have ALK mutations/rearrangements, so while amazing, this finding is not applicable to all patients [2].

[0] https://www.nejm.org/doi/full/10.1056/NEJMoa2027187

[1] https://ascopubs.org/doi/10.1200/JCO.24.00581

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597761/

Can you elaborate? In particular, this:

>>>>Five-year data indicate a significant progression-free survival benefit, with 60% of patients free of progression.

So far im with you.

>>>>Even after 60.2 months of follow-up, the median progression-free survival has not yet been reached [1]

This sounds awful? Or contradictory at best?

>>>>Even after 60.2 months of follow-up, the median progression-free survival has not yet been reached [1]

> This sounds awful? Or contradictory at best?

No, quite amazing. At 5 years more than 50% of participants are progression-free. That's indeed off the charts for a metastatic lung cancer.

I believe the median progression-free survival is the length of time where 50% of people are still free from progression. The numbers you mentioned would mean that we don't know how long that is for this treatment but it's definitely longer than 5 years. That sounds pretty good depending on the type of cancer and stage when treatment started.

> it is fully approved for ALK+ NSCLC and has been since 2015.

Not exactly. FDA granted it an orphan drug designation in 2014, and then full approval for second- or third-line therapies in 2018 (on the basis of a Phase I/II study). The Phase III study (NCT03052608) is the gift that keeps on giving - it ran 2017-2020, and the progression-free survival in the lorlatinib arm is 60% vs 8% for the control.

It also inherently takes at least 5 years from when a study starts to show that progression-free survival is at least 5 years.