What is your preferred first line therapy in metastatic ALK+ NSCLC?

For patients with known CNS metastases at baseline, lorlatinib may potentially offer better CNS disease control, albeit with more toxicity relative to brigatinib/alectinib. Brigatinib is more convenient in terms of dosing from the patient perspective (one tablet once daily versus up to four twice da...

There are multiple therapeutic options for patients with ALK rearranged non-small cell lung cancer. We now have 3 phase 3 trials that have shown that next generation ALK directed therapy is superior to crizotinib for advanced adenocarcinoma patients harboring an ALK rearrangement. Alectinib, Brigati...

There is no head to head data that suggest superiority of alectinib over brigatinib or vice versa, nor are those data likely to become available. Both have demonstrated significant (and similar) PFS gains over crizotinib and both are associated with significant CNS activity in terms of time to CNS p...

There are several right answers here. Clearly, we favor TKI therapy over chemotherapy (and ALK+ NSCLC is not an immunotherapy-responsive tumor). Crizotinib was the first but CNS coverage is its Achilles heel. Ceritinib is approved but is the least well tolerated of the bunch. Sorting out alectinib, ...

I use alectinib because the data is more mature, experience, and there are no cross trial comparisons.

Generally choose alectinib. Now that lorlatinib is approved, may consider this drug particularly in patients with brain mets.

Tough question, and it boils down in my mind to lorlatinib vs brig or alectinib. For someone who’s younger and wants the therapy with the best outcome we know (though not in head to head), I follow CROWN and use lorlatinib. For someone older or anyone on high doses of statin already (rare) or who's ...

Lorlatinib outperformed crizotinib based on the CROWN data, with a recent update at 7-year follow-up with median PFS not yet met for lorlatinib. No head-to-head comparison with 2nd generation ALK TKIs. For patients with poor prognostic features such as variant 3, known CNS metastases at baseline, ad...

My preferred frontline choice is always patient-specific. In patients who present with CNS disease, I prefer initiating lorlatinib. In many patients, I have initiated alectinib. The decision is challenging because there is no head-to-head comparison to help guide out selection.

Alectinib, followed by lorlatinib if there is no CNS involvement. If the patient has CNS involvement, I go straight to lorlatinib. Thanks.