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Lorlatinib Superior To Crizotinib in ALK+ NSCLC
According to a subgroup analyses of the CROWN trial, first-line lorlatinib offered superior progression-free survival (PFS) benefit to crizotinib in Asian patients with ALK+ non-small-cell lung cancer (NSCLC; Annals of Oncology, S949-S1039.).
“Lorlatinib, a 3rd-generation ALK inhibitor, significantly prolonged progression-free survival v.s. crizotinib in the CROWN trial in patients with untreated ALK-positive non-small cell lung cancer. We report data from the Asian subgroup of CROWN,” explained Qing Zhou, MD, PhD Department Of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangzhou, China, and colleagues.
In this phase 3 trial, patients with ALK-positive advanced NSCLC were randomized to receive either lorlatinib or crizotinib. Patients were stratified by the presence of brain metastases and ethnicity (Asian/non-Asian). The primary endpoint was PFS by blinded independent central review.
In the Asian subgroup, 120 patients were randomized - 59 to lorlatinib and 62 to crizotinib. Researchers found that lorlatinib prolonged PFS and increased overall and intracranial response when compared to crizotinib. The event-free survival at 12 months was 72% in the lorlatinib group (95% CI; 59–82) and 48% (95%; 32–62). The intracranial objective response rate (iORR) was 72.7% (95% CI; 39.0–94.0) for lorlatinib and 25.0% (95% CI; 7.3–52.4) for crizotinib (95% CI; 7.3–52.4).
The most common treatment-related adverse events included: hypertriglyceridemia, hypercholesterolemia, edema, and weight increase (lorlatinib), and nausea, diarrhea, vomiting, vision disorder, and constipation (crizotinib). Although more patients reported grade 3/4 AEs in the lorlatinib arm (78%), fewer discontinued treatment.
“In the Asian subgroup, a consistent and clinically meaningful improvement in PFS was observed for lorlatinib v.s, crizotinib. The efficacy and safety of lorlatinib vs crizotinib in the Asian subgroup of CROWN were consistent with the overall population,” concluded Dr Zhou et al.—Alexandra Graziano
