[dannykwells]

Note that this drug is not new - it is fully approved for ALK+ NSCLC and has been since 2015.

It's not clear why these data are just coming out now or what is different from the original trials run in this setting.

https://en.wikipedia.org/wiki/Lorlatinib

[westcort]

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/

[IG_Semmelweiss]

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?

[ilya_m]

> 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.

[garrison]

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