Lorlatinib

The phase III CROWN trial (NCT03052608) included patients with advanced ALK-rearranged NSCLC who had received no prior systemic therapy for metastatic disease. The trial randomly assigned 296 patients to receive either lorlatinib (100 mg daily) or crizotinib (250 mg twice daily). The primary end point was PFS as determined by blinded independent central review.[66][Level of evidence B1]

The phase III CROWN trial (NCT03052608) included patients with advanced ALK-rearranged NSCLC who had received no prior systemic therapy for metastatic disease. The trial randomly assigned 296 patients to receive either lorlatinib (100 mg daily) or crizotinib (250 mg twice daily). The primary end point was PFS as determined by blinded independent central review.[66][Level of evidence B1]

With a median follow-up of 60.2 months, the median PFS was not reached (NR) (95% CI, 64.3–NR) in patients who received lorlatinib. With a median follow-up of 55.1 months, the median PFS was 9.1 months (95% CI, 7.4–10.9) in patients who received crizotinib (HR, 0.19; 95% CI, 0.13–0.27).[67]

The phase III CROWN trial (NCT03052608) included patients with advanced ALK-rearranged NSCLC who had received no prior systemic therapy for metastatic disease. The trial randomly assigned 296 patients to receive either lorlatinib (100 mg daily) or crizotinib (250 mg twice daily). The primary end point was PFS as determined by blinded independent central review.[66][Level of evidence B1]

The 5-year PFS rate was 60% (95% CI, 51%–68%) in patients who received lorlatinib and 8% (95% CI, 3%–14%) in patients who received crizotinib.

The phase III CROWN trial (NCT03052608) included patients with advanced ALK-rearranged NSCLC who had received no prior systemic therapy for metastatic disease. The trial randomly assigned 296 patients to receive either lorlatinib (100 mg daily) or crizotinib (250 mg twice daily). The primary end point was PFS as determined by blinded independent central review.[66][Level of evidence B1]

The median time to intracranial progression was not reached (95% CI, NR–NR) in the lorlatinib group and was 16.4 months (95% CI, 12.7–21.9) in the crizotinib group (HR, 0.06; 95% CI, 0.03–0.12).

The phase III CROWN trial (NCT03052608) included patients with advanced ALK-rearranged NSCLC who had received no prior systemic therapy for metastatic disease. The trial randomly assigned 296 patients to receive either lorlatinib (100 mg daily) or crizotinib (250 mg twice daily). The primary end point was PFS as determined by blinded independent central review.[66][Level of evidence B1]

Lorlatinib was associated with more grade 3 to 4 adverse events than crizotinib (72% vs. 56%), the most common being altered lipid levels. Treatment discontinuation occurred in 7% of patients who received lorlatinib and 9% of patients who received crizotinib.[66]