Early lipid-lowering therapy within 30 days of lorlatinib in NSCLC was associated with lower 1-year all-cause mortality (16.1% vs 26.4%; RR 0.61, 95% CI 0.46-0.81; p=0.0004).
Cohort (n=774)
Yes
Does early lipid-lowering therapy initiation reduce mortality and vascular events in adults with NSCLC treated with lorlatinib?
Early initiation of lipid-lowering therapy in lorlatinib-treated NSCLC patients is associated with significantly lower 1-year mortality, venous thromboembolism, and hospitalizations.
Effect estimate: RR 0.61 (95% CI 0.46-0.81)
Absolute Event Rate: 16.1% vs 26.4%
p-value: p=0.0004
8597 Background: Lorlatinib improves outcomes in NSCLC but commonly causes marked hyperlipidemia, prompting initiation of lipid-lowering therapy (LLT). Beyond lipid control, LLT may be associated with vascular events; however, its association with thromboembolism, healthcare utilization, and mortality among lorlatinib-treated patients has not been characterized in real-world cohorts. Methods: Using TriNetX, we identified adults with NSCLC who received lorlatinib (index = first lorlatinib record). Patients were grouped by early LLT initiation within 30 days of index versus no LLT within 30 days. LLT included statins, ezetimibe, PCSK9 inhibitors, or fibrates. Cohorts were balanced 1:1 using propensity score matching on demographics and baseline comorbidities. Outcomes were assessed through 365 days; patients with prior outcome documentation were excluded. Results: After matching, 387 patients per cohort were analyzed. Early LLT was associated with lower all-cause mortality at 365 days (16.1% vs 26.4%; risk ratio RR 0.61, 95% CI 0.46-0.81; p=0.0004) and improved time to death (hazard ratio 0.60, 95% CI 0.44-0.82). Early LLT was also associated with lower venous thromboembolism (6.2% vs 12.1%; RR 0.51, 95% CI 0.30-0.86; p=0.0093) and fewer inpatient hospitalizations (14.6% vs 23.6%; RR 0.62, 95% CI 0.40-0.97; p=0.0320). Emergency department visits were numerically lower (8.3% vs 13.9%; RR 0.59, 95% CI 0.35-1.00; p=0.0467). No significant differences were observed for acute kidney injury or major adverse cardiovascular events. Conclusions: In a real-world propensity-matched cohort of lorlatinib-treated NSCLC patients, LLT initiated within 30 days was associated with lower 1-year mortality, venous thromboembolism, and hospitalization. Given the frequency of lorlatinib-associated dyslipidemia, these findings support early lipid monitoring and timely LLT initiation in practice. Prospective studies are warranted to confirm these associations. 365-day outcomes after matching. Outcome Early LLT (n=387) No early LLT (n=387) RR (95% CI) HR (95% CI) p All-cause mortality 16.1% 26.4% 0.608 (0.458-0.806) 0.597 (0.435-0.818) 0.0004; log-rank 0.001 Venous thromboembolism 6.2% 12.1% 0.509 (0.302-0.857) — 0.0093 Inpatient hospitalization 14.6% 23.6% 0.619 (0.396-0.967) — 0.0320 ED visit 8.3% 13.9% 0.593 (0.352-1.001) — 0.0467 Acute kidney injury 5.4% 7.1% 0.769 (0.429-1.378) — 0.3758 MACE 4.6% 4.6% 1.006 (0.511-1.979) — 0.9868
Gopu et al. (Thu,) conducted a cohort in non-small cell lung cancer (n=774). Early lipid-lowering therapy (LLT) vs. No early LLT within 30 days was evaluated on All-cause mortality (RR 0.61, 95% CI 0.46-0.81, p=0.0004). Early lipid-lowering therapy within 30 days of lorlatinib in NSCLC was associated with lower 1-year all-cause mortality (16.1% vs 26.4%; RR 0.61, 95% CI 0.46-0.81; p=0.0004).