Jajja, Salman

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

5079 Background: Treatment sequencing in metastatic castration-resistant prostate cancer (mCRPC) after ADT and ARPI exposure varies in practice. While 177 Lu-PSMA use is expanding in routine practice, real world head to head comparisons with docetaxel in ARPI-exposed mCRPC are limited, particularly for short-term outcomes and treatment related acute care utilization. Methods: Using TriNetX, adults > 18 years of age with metastatic prostate cancer and prior ARPI exposure who initiated 177 Lu-PSMA or docetaxel were identified (index = first administration). Cohorts were balanced with 1:1 propensity score matching (PSM) on demographics and baseline comorbidities. Outcomes from day 1–180 post-index included all-cause mortality (primary), hospitalization, acute kidney injury (AKI; ICD-10 N17), and thromboembolic/ischemic events (ICD-10 I21/I26/I63/I82). For each outcome, patients with prior documentation of that outcome were excluded. Outcomes are reported as risks and risk ratios (RR) with 95% confidence intervals. Results: Before matching, 563 patients initiated 177 Lu-PSMA-617 and 8,749 initiated docetaxel; after 1:1 PSM, 497 patients per cohort were analyzed. At 180 days, all-cause mortality was 7.3% (36/494) with 177 Lu-PSMA-617 versus 12.2% (60/491) with docetaxel (RR 0.60, 95% CI 0.40–0.88). Hospitalization occurred in 7.2% (21/290) versus 21.1% (52/247) (RR 0.34, 95% CI 0.21–0.55). In a separate matched renal-safety analysis (480 per cohort), AKI occurred in 2.8% (11/390) versus 9.0% (36/399) (RR 0.31, 95% CI 0.16–0.60). Thromboembolic/ischemic events were 3.8% (15/394) versus 6.4% (26/404) (RR 0.59, 95% CI 0.32–1.10). Conclusions: In ARPI-exposed mCRPC, 177 Lu-PSMA was associated with lower 180-day mortality risk and substantially fewer hospitalizations than docetaxel, with a lower risk of AKI. These findings highlight a potential short-term effectiveness and acute-care utilization advantage of 177 Lu-PSMA in routine practice and support further prospective evaluation. Key 180-day outcomes after matching. Outcome 177 Lu-PSMA Docetaxel Effect estimate (180 days) All-cause mortality 36/494 (7.3%) 60/491 (12.2%) RR 0.596 (0.402-0.884) Hospitalization 21/290 (7.2%) 52/247 (21.1%) RR 0.344 (0.213-0.554); Acute kidney injury (AKI)* 11/390 (2.8%) 36/399 (9.0%) RR 0.312 (0.163-0.595) Thromboembolic/ischemic† 15/394 (3.8%) 26/404 (6.4%) RR 0.592 (0.318-1.100) *AKI analysis used a separate matched run (480 per cohort). †Composite of I21, I26, I63, I82.