4 ms·

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

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

westcort 2y ago
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 https://www.nejm.org/doi/full/10.1056/NEJMoa2027187 [1] https://ascopubs.org/doi/10.1200/JCO.24.00581 https://ascopubs.org/doi/10.1200/JCO.24.00581 [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597761/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597761/
- IG_Semmelweiss 2y ago
  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 2y ago
    >>>>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.
  - fredophile 2y ago
    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.
  - deleted 2y ago
    [deleted]
ilya_m 2y ago
> 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 2y ago
  It also inherently takes at least 5 years from when a study starts to show that progression-free survival is at least 5 years.

westcort 2y ago

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 https://www.nejm.org/doi/full/10.1056/NEJMoa2027187 [1] https://ascopubs.org/doi/10.1200/JCO.24.00581 https://ascopubs.org/doi/10.1200/JCO.24.00581 [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597761/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597761/

IG_Semmelweiss 2y ago
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 2y ago
  >>>>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.
- fredophile 2y ago
  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.
- deleted 2y ago
  [deleted]

ilya_m 2y ago

> 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 2y ago
It also inherently takes at least 5 years from when a study starts to show that progression-free survival is at least 5 years.