Top Line: First-line lorlatinib monotherapy for ALK-rearranged non-small cell lung cancer (NSCLC) too advanced for definitive treatment results in the longest progression-free survival times ever recorded for both this disease or any metastatic solid tumor treated with any targeted systemic therapy.
The Study: We’ve known for a while that the CROWN trial demonstrated an early and clear advantage in disease control with lorlatinib versus crizotinib for this population, but we didn’t know until now just how remarkably effective this newer-gen ALK-inhibitor really is. As an important reminder, the vast majority of patients (93%) had distant mets at enrollment including 25% with brain mets. Five-year results were presented this week at ASCO 2024 to reveal a median progression-free survival (PFS) time across the 149 enrollees in the lorlatinib has yet to be reached. Rates of PFS at 5 years were 60% versus 8% with crizotinib, and no new ALK-resistance mutations have been detected. The most common higher-grade toxicity with lorlatinib is hyperlipidemia. A final reminder for radiation oncologists: for the 5% of patients with NSCLC that harbor ALK-rearrangements, careful observation of asymptomatic brain mets on lorlatinib can be considered.
TBL:More than half of patients receiving upfront lorlatinib monotherapy for metastatic ALK-rearranged NSCLC are without evidence of disease progression at 5 years. | Solomon, J Clin Oncol 2024
The Study: We’ve known for a while that the CROWN trial demonstrated an early and clear advantage in disease control with lorlatinib versus crizotinib for this population, but we didn’t know until now just how remarkably effective this newer-gen ALK-inhibitor really is. As an important reminder, the vast majority of patients (93%) had distant mets at enrollment including 25% with brain mets. Five-year results were presented this week at ASCO 2024 to reveal a median progression-free survival (PFS) time across the 149 enrollees in the lorlatinib has yet to be reached. Rates of PFS at 5 years were 60% versus 8% with crizotinib, and no new ALK-resistance mutations have been detected. The most common higher-grade toxicity with lorlatinib is hyperlipidemia. A final reminder for radiation oncologists: for the 5% of patients with NSCLC that harbor ALK-rearrangements, careful observation of asymptomatic brain mets on lorlatinib can be considered.
TBL:More than half of patients receiving upfront lorlatinib monotherapy for metastatic ALK-rearranged NSCLC are without evidence of disease progression at 5 years. | Solomon, J Clin Oncol 2024