Top Line: How many ALK-inhibitors are better than crizotinib for first-line treatment of ALK-rearrangement positive NSCLC?'
The Study: Alectinib (preferred), brigatinib, and ceritinib are all approved for first-line therapy for advanced, ALK-rearrangement positive NSCLC. Currently, lorlatinib is recommended after progression on a first-line ALK-inhibitor. That’s because lorlatinib can be effective against ALK-resistance mutations. In the CROWN trial, though, lorlatinib was pitted against the embattled crizotinib as first-line therapy. You know, maybe it’s time to throw in the towel for poor crizotinib and have some of the next-generation ALK-inhibitors actually face each other. In the CROWN Trial, close to 300 patients with advanced NSCLC and an ALK mutation were randomized to first-line crizotinib or lorlatinib. Lorlatinib doubled 12-month PFS from 39→ 78%. Objective response rate was also improved from 58→ 76%. Lorlatinib has been touted to be better at crossing the blood brain brain barrier. In a small subset of patients (~15 in each arm) with brain metastases, intracranial response was 82 vs 23% and >⅔ of those in the lorlatinib arm had a complete intracranial response. This was an interim analysis, so overall survival results were not yet mature.
TBL: Add lorlatinib to the list of ALK-inhibitors that improve PFS over crizotinib in first-line setting for advanced, ALK-rearrangement positive NSCLC. | Shaw, N Engl J Med 2020