劳拉替尼与克唑替尼治疗既往未接受治疗的晚期ALK阳性非小细胞肺癌——ASCO邮报

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As reported in the Journal of Clinical Oncology by Benjamin J. Solomon, MBBS, PhD, and colleagues, analysis of 5-year outcomes in the phase III CROWN trial showed that median progression-free survival had not been reached in previously untreated patients receiving lorlatinib vs a median of 9.1 months in patients receiving crizotinib for advanced ALK-positive non–small cell lung cancer (NSCLC). The trial supported the March 2021 expanded approval of lorlatinib in this setting on the basis of improved progression-free survival and intracranial activity vs crizotinib, and converted the 2018 accelerated approval to regular approval in this setting. In the international, open-label trial, 296 patients with ALK-positive NSCLC were randomly assigned to receive lorlatinib at 100 mg once daily (n = 149) or crizotinib at 250 mg twice daily (n = 147) in 28-day cycles. The current analysis presents 5-year outcomes. After 5 years of follow-up, median progression-free survival has yet to be reached in the lorlatinib group, corresponding to the longest progression-free survival ever reported with any single-agent molecular targeted treatment in advanced NSCLC and across all metastatic solid tumors. These results, coupled with prolonged intracranial efficacy and absence of new safety signals, represent an unprecedented outcome for patients with advanced ALK-positive NSCLC and set a new benchmark for targeted therapies in cancer. — Benjamin J. Solomon, MBBS, PhD, and colleagues Tweet this quote At data cutoff for the current analysis (October 2023), median follow-up for progression-free survival was 60.2 months in the lorlatinib group and 55.1 months in the crizotinib group. Median progression-free survival was not reached (95% confidence interval = 64.3 months to not reached) in the lorlatinib group vs 9.1 months (95% CI = 7.4–10.9 months) in the crizotinib group (hazard ratio = 0.19,95% CI = 0.13–0.27). Rates at 4 and 5 years were 63% vs 10% and 60% vs 8%, respectively. Among 35 vs 38 patients with measureable or nonmeasurable baseline brain metastases, median progression-free survival was not reached (95% CI = 32.9 months to not reached) among patients receiving lorlatinib vs 6.0 months (95% CI = 3.7–7.6 months) among those receiving crizotinib (HR = 0.08,95% CI = 0.04–0.19). Among all patients, median time to intracranial progression was not reached (95% CI = not reached to not reached) in the lorlatinib group vs 16.4 months (95% CI = 12.7–21.9 months) in the crizotinib group (HR = 0.06,95% CI = 0.03–0.12). The likelihood of remaining free of intracranial progression at 5 years was 92% vs 21%, respectively. Emerging new ALK resistance mutations were detected at the end of crizotinib treatment; none were detected in circulating tumor DNA at the end of lorlatinib treatment. The safety profiles of lorlatinib and crizotinib were consistent with those seen in prior analyses. The investigators concluded, “After 5 years of follow-up, median progression-free survival has yet to be reached in the lorlatinib group, corresponding to the longest progression-free survival ever reported with any single-agent molecular targeted treatment in advanced NSCLC and across all metastatic solid tumors. These results, coupled with prolonged intracranial efficacy and absence of new safety signals, represent an unprecedented outcome for patients with advanced ALK-positive NSCLC and set a new benchmark for targeted therapies in cancer. ” Dr. Solomon, of Peter MacCallum Cancer Centre, Melbourne, is the corresponding author for the Journal of Clinical Oncology article. Disclosure: The study was supported by Pfizer. For full disclosures of the study authors, visit ascopubs. org.