Research Article|Articles in Press, 100499

Asian Subgroup Analysis of the Randomized Phase 3 CROWN Study of First-Line Lorlatinib vs Crizotinib in Advanced ALK-Positive Non-Small Cell Lung Cancer

Open AccessPublished:March 10, 2023DOI:
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      Lorlatinib is a potent, third-generation inhibitor of anaplastic lymphoma kinase (ALK). In the planned interim analysis of the ongoing, Phase 3, randomized, global CROWN trial (NCT03052608), lorlatinib resulted in significantly longer progression-free survival (PFS) than crizotinib in patients with previously untreated, advanced, ALK-positive non-small cell lung cancer. Here, we present a subgroup analysis of Asian patients in the CROWN study.


      Patients received lorlatinib 100 mg once daily or crizotinib 250 mg twice daily. The primary endpoint was PFS assessed by blinded independent central review (BICR). Objective response rate (ORR), intracranial ORR, safety, and select biomarkers were secondary endpoints.


      At data cutoff (September 20, 2021), 120 patients were included in the Asian intention-to-treat subgroup (lorlatinib n=59; crizotinib n=61). At 36 months, 61% (95% confidence interval [CI], 47–72) and 25% (95% CI, 12–41) of patients in the lorlatinib and crizotinib groups, respectively, were alive without disease progression (hazard ratio for disease progression by BICR or death: 0.40; 95% CI, 0.23–0.71). ORR was 78% (95% CI, 65–88) vs 57% (95% CI, 44–70) for patients treated with lorlatinib and crizotinib, respectively. In patients with measurable and/or non-measurable brain metastases at baseline, intracranial ORR was 73% (95% CI, 39–94) vs 20% (95% CI, 4–48) for patients treated with lorlatinib and crizotinib, respectively. Hypercholesterolemia, hypertriglyceridemia, and edema were the most commonly reported adverse events with lorlatinib.


      Lorlatinib efficacy and safety in the Asian subgroup of CROWN were consistent with those in the overall population.