77 Background: The incidence of metastatic hormone-sensitive prostate cancer (mHSPC) is increasing in the US, likely due to a decrease in screening practices. There has also been a rapid increase in recent years in the number of treatment options that can improve progression-free and overall survival (OS) for these patients. The objective of the current study was to evaluate the clinical outcomes among patients with mHSPC treated in contemporary US clinical practice (2020 to 2025). Methods: This retrospective, observational cohort study used data from PRECISION, a harmonized dataset on advanced prostate cancer in patients in the US treated in a range of clinical settings. Patients aged ≥18 years who were diagnosed with mHSPC during 01/01/2020–01/01/2024 and who initiated ≥1 therapy (index date = first-line [1L] treatment initiation) were included. The study period was from 01/01/2010 to 06/30/2025. Patient characteristics at mHSPC diagnosis and treatment utilization were evaluated descriptively. Castration resistance-free survival (CRFS; defined as the time to castration-resistant prostate cancer or death) and OS were evaluated from index using Kaplan–Meier analysis. Results: A total of 27,708 patients were included (median age, 72 years); 20,015 (72%) were treated in community urology, 4994 (18%) in community oncology, and 2669 (10%) in academic oncology centers at index. Almost half of patients (47%) initiated 1L treatment with androgen-deprivation therapy (ADT) monotherapy, 44% initiated a 1L doublet regimen (36% ADT + androgen receptor pathway inhibitor [ARPI], 5% 1L ADT + radiotherapy, 2% 1L ADT + docetaxel), and 5% a 1L triplet regimen (ADT + radiotherapy + ARPI or docetaxel); the remaining patients received other regimens. The 5-year CRFS rate was 41%; this was significantly higher in patients with a 1L doublet (45%) or triplet (58%) regimen compared with patients with 1L ADT monotherapy (31%; p<0.001). Similarly, the 5-year OS rate was 59% overall and was significantly higher in patients with a 1L doublet (61%) or triplet (59%) regimen compared with patients with 1L ADT monotherapy (55%; p<0.001) (Table). Conclusions: Though both CRFS and OS rates appear to be increasing among real-world patients with mHSPC, >40% of patients in this study died within 5 years of initiating 1L treatment. Patients who received guideline-recommended combined systemic treatment regimens experienced improved CRFS and OS, confirming the importance of implementing therapies in practice that prolong survival. CRFS and OS rates from start of 1L therapy, by therapy type. CRFS rate (%) OS rate (%) 1 y 2 y 3 y 4 y 5 y 1 y 2 y 3 y 4 y 5 y Overall 68 58 51 46 41 93 84 76 67 59 ADT monotherapy 59 49 41 36 31 92 83 74 65 55 Doublet therapy 72 62 55 49 45 94 85 76 68 61 Triplet therapy 85 77 70 68 58 94 89 82 74 59

60 Background: With the emergence of several newly approved therapies for mCRPC, data on the optimal treatment sequence are limited. The aim of this study is to understand the treatment patterns of mCRPC patients who received at least one androgen receptor pathway inhibitor (ARPI) or taxane at the VAHCS, an equal-access healthcare system. Methods: This is a retrospective, observational study utilizing VAHCS claims data from patients diagnosed with mCRPC between January 1, 2018 and February 29, 2024 nationwide. Patients with mCRPC who received first-line (1L) therapy of ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide; [ARPI cohort]) or a taxane (docetaxel or cabazitaxel; [taxane cohort]) were included; 1L therapy was defined as the first prescription for ARPI or taxane after prostate cancer diagnosis. Thus, though the 1L treatment could have been for metastatic castration-sensitive prostate cancer or mCRPC, all patients ultimately progressed to mCRPC. Patients who received radiation within 6 months or any other chemotherapy prior to 1L therapy, or who were diagnosed with any other cancers (excluding non-melanoma skin cancer) prior to mCRPC were excluded. Results: In total, 2982 patients with mCRPC who met the inclusion criteria were identified, which included a large cohort of African American patients (25%). Although most patients received an ARPI in the 1L (2828 patients, 95%), 154 patients (5%) received 1L taxane. Patients in the ARPI cohort were significantly older than those in the taxane cohort (median 74 vs 68 years; p<0.001). Patients in the ARPI cohort received mainly 1L abiraterone or enzalutamide with a similar frequency (both 48%), and docetaxel was the most common treatment for patients who had received 1L taxane (97%). Overall, 1223 patients (41% of all patients) received second-line (2L) therapy. Taxanes were more frequently used in 2L treatment (16%) compared with 1L; however ARPI, especially abiraterone (27%) and enzalutamide (42%), remained the most frequent choices for 2L treatment. Back-to-back ARPI use in 1L and 2L was the most common treatment sequence, with 74% of patients who received 2L abiraterone having been treated with 1L enzalutamide, and 87% of patients who received 2L enzalutamide having been treated with 1L abiraterone. Few patients (11% of all patients) received third-line (3L) treatments. Conclusions: In the VA equal-access healthcare system, back-to-back ARPIs remained the most common treatment sequence for the management of patients with mCRPC with few patients receiving 3L treatment. Further research is planned to investigate clinical outcomes, adverse events, and healthcare resources utilization associated with these treatment sequences to hopefully identify an optimal mCRPC management.

63 Background: 177 Lu-PSMA-617, a prostate-specific membrane antigen (PSMA)-targeting radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC), received FDA approval in March 2022 for the treatment of adult patients with PSMA-positive mCRPC who have received both an androgen receptor pathway inhibitor (ARPI) and a taxane-based chemotherapy. Outside of clinical trials, limited real-world evidence evaluating the effectiveness of 177 Lu-PSMA-617 has been reported. The aim of the current study was to evaluate patient characteristics and overall survival (OS) among patients diagnosed with mCRPC who were treated with 177 Lu-PSMA-617 within a large-scale real-world cohort. Methods: This retrospective, observational study used the IQVIA PharMetrics Plus claims data from July 1, 2013 to December 31, 2023, and linked social determinants of health data as well as mortality data to obtain month and year of death. Adult men with mCRPC who had received 177 Lu-PSMA-617 were included (first receipt of 177 Lu-PSMA-617 = index date). Patient demographics and characteristics were evaluated descriptively; patient demographics were reported on the index date and clinical characteristics were evaluated over the 12 months prior to index date. OS was measured from the start of the first 177 Lu-PSMA-617 treatment until death or end of available follow-up, and assessed using Kaplan–Meier analysis. Results: A total of 643 patients were included in the analysis; median age was 69 years. Treatment for the majority of patients (490/643 [76.2%]) was managed by oncologists (169 [26.3%] of which had specialty in radiation oncology). White patients (292 [72.8%]) made up the largest part of the patient population followed by Black (37 [9.2%]), Hispanic (23 [5.7%]), and Asian (8 [2.0%]). Most patients had multiple comorbidities with either one (226/643 [35.1%]) or two (224/643 [34.8%]) sites of metastasis. Most patients experienced bone metastases (581/643 [90.4%]); 284/643 (44.2%) also experienced visceral metastases of which the liver was the most common site (78/643 [12.1%]). The median OS from start of 177 Lu-PSMA-617 therapy was 15.3 months (95% confidence interval [CI]: 14.6–16.3); a total of 137/643 (21.3%) patients died. OS was analyzed in different patient subgroups and no major differences were observed by metastatic site, number of metastatic sites, race, or age. Conclusions: To our knowledge, this is the first large-scale study reporting OS with 177 Lu-PSMA-617 in clinical practice. OS observed with 177 Lu-PSMA-617 in this study (median: 15.3 months) was consistent with results from the VISION Phase III clinical trial (median: 15.3 months; NCT03511664). Furthermore, 177 Lu-PSMA-617 demonstrated similar survival across different patient subgroups.

59 Background: There are several real-world data sources for prostate cancer (PC), each with its own limitations; the most notable limitation is an incomplete picture of the multidisciplinary clinical management of PC. The PRECISION data platform, the largest, most comprehensive, and continually updated real-world evidence source on patients with advanced PC to date, tries to address this limitation and shed light on PC management in both urology and oncology practices in both academic and community settings in the US. The platform includes a wide variety of PC-specific data variables among patients with metastatic hormone-sensitive PC (mHSPC) and metastatic castration-resistant PC (mCRPC) treated across the US. This study aims to provide an overview of the characteristics, treatment patterns, and clinical outcomes among patients with mHSPC and mCRPC included in PRECISION to date. Methods: A retrospective cohort study that included patients with a diagnosis of mHSPC or mCRPC (index date) in PRECISION between 2018 and 2024 (cohorts could overlap). For each cohort, patient characteristics and treatment patterns were evaluated descriptively. Results: The PRECISION platform currently includes 72,855 and 33,538 patients with mHSPC and mCRPC, respectively. Among the mHSPC cohort, the mean ± standard deviation (SD) age was 74.5±9.4 years; 67% and 33% were treated at oncology and urology centers, respectively; 40% and 60% were from academic and community settings, respectively. The average ± SD time from mHSPC to mCRPC was 11.2±11.7 months. Overall, 77.6% of patients were treated with androgen-deprivation therapy (ADT), of whom 64.7% had ADT combined with androgen receptor pathway inhibitors (ARPIs) including abiraterone acetate, enzalutamide, and apalutamide. Among the mCRPC cohort, the mean ± SD age was 74.1±9.3 years; similar treatment setting patterns as mHSPC were observed. Overall, 74.6% initiated a first-line (1L) therapy on/after mCRPC diagnosis; 52.1% had 1L ARPIs, 16.2% 1L immunotherapy, and 4.6% 1L taxane chemotherapy. In addition, 2.2% of patients received the recently US FDA-approved therapy, lutetium-177 vipivotide tetraxetan, at some point during their mCRPC disease duration. Conclusions: This analysis provides key insights into the patients included in the PRECISION data platform. This multidisciplinary dataset provides a 70/30 split between oncology and urology centers, and a 40/60 split between academic and community settings. The observed clinical profile, treatment patterns, and outcomes comprise the most comprehensive representation of current treatment practice in the US. Future analyses of clinical outcomes with existing and novel therapies could contribute significantly to our understanding of opportunities to improve the treatment of patients with mHSPC and mCRPC in the US.

e17035 Background: 177 Lu-PSMA-617 was approved in March 2022 for patients with mCRPC pretreated with an androgen receptor pathway inhibitor (ARPI) and a taxane. There are limited data on the effectiveness of treatments post- 177 Lu-PSMA-617. The aim of this study was to describe prostate-specific antigen (PSA) responses among patients with mCRPC receiving a guideline-recommended therapy as the next therapy after 177 Lu-PSMA-617 treatment. Methods: This retrospective, observational study used real-world data from the PRECISION data platform, a proprietary dataset developed by Novartis, comprised of patient-level electronic health record and claims data that represent the US advanced prostate cancer population in the community, academic, urology, and medical oncology settings. Patients with mCRPC who received any guideline-recommended therapy at least 14 days after treatment with 177 Lu-PSMA-617 between March 23, 2022 and July 31, 2024 were included. Guideline-recommended therapies included abiraterone, enzalutamide, darolutamide, apalutamide, cabazitaxel, docetaxel, pembrolizumab, sipuleucel-T, niraparib, olaparib, talazoparib, rucaparib, and radium-223. Patients’ PSA values while on 177 Lu-PSMA-617 treatment were compared with their PSA values during the subsequent therapy course. Proportions of patients achieving reductions in PSA levels ≥50% (PSA50) and ≥80% (PSA80) were estimated. All analyses were descriptive. Results: A total of 152 patients receiving any subsequent guideline-recommended therapy after 177 Lu-PSMA-617 were identified. Mean age was 72.1 years. Most patients received an ARPI (n=93, 61.2%) – abiraterone (n=38), enzalutamide (n=37), darolutamide (n=10), or apalutamide (n=8) – as their subsequent therapy. Of patients who received a taxane (n=42, 27.6%), 24 received cabazitaxel and 18 received docetaxel. Median time to initiation of subsequent therapy was 206 days (interquartile range [IQR] 101–301 days) from 177 Lu-PSMA-617 initiation and 44 days (IQR 17–119 days) from 177 Lu-PSMA-617 discontinuation. Overall, among patients with sufficient information for PSA evaluation (n=30), 46.7% achieved PSA50 and 40.0% PSA80 post- 177 Lu-PSMA-617. Among patients receiving an ARPI, PSA50 was observed in 11/18 (61.1%) and PSA80 in 10/18 (55.6%). Among patients receiving a taxane, PSA50 and PSA80 were seen in 3/12 (25.0%) and 2/12 (16.7%), respectively. Conclusions: In this real-world analysis, the majority of patients who received guideline-recommended therapies after 177 Lu-PSMA-617 achieved at least a PSA50 response, suggesting that 177 Lu-PSMA-617 treatment does not preclude response to other subsequent therapies.

e17048 Background: 177 Lu-PSMA-617 was approved by the US Food and Drug Administration in March 2022 for the treatment of patients with prostate-specific membrane antigen (PSMA) positive metastatic castration resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition (ARPI) and taxane-based chemotherapy. This study describes characteristics of patients treated with 177 Lu-PSMA-617, treatment patterns and early trends in 177 Lu-PSMA-617 utilization by US urologists (URO) and medical oncologists (ONC). Methods: This retrospective cohort study identified adult patients with ≥1 claim for 177 Lu-PSMA-617 between 3/1/22 and 6/30/23 (first claim = index date) from the IQVIA open-source pharmacy and medical claims database. Patients were grouped by the physician specialty of the treating/referring physician. Patient characteristics were assessed within the 6 months prior to 177 Lu-PSMA-617 initiation. Prior prostate cancer treatments were assessed over all available pre-index data. Results: Overall 1,394 patientstreated with 177 Lu-PSMA-617 were identified during the first 16 months post-approval; 76.9% treated by an ONC and 23.1% treated by a URO. The mean age overall was 72.1 years; most patients were aged 65 and older (ONC, 83.3%; URO, 84.8%). Most patients had bone metastases (ONC, 88.0%; URO, 86.3%) and over one-third had visceral metastases (ONC, 34.6%; URO 35.7%). URO treated a higher proportion of patients with only lymph node metastases (5.9%) than oncologists (2.6%). Prior to 177 Lu-PSMA-617, the vast majority of patients received ARPI and/or taxanes (ONC, 88.2%; URO, 89.4%). Use of 177 Lu-PSMA-617 has steadily increased over the 16 months since approval with over five times as many patients being treated by ONC and URO in the first half of 2023. Conclusions: This is the first large-scale study describing 177 Lu-PSMA-617 patient characteristics, prostatic cancer metastatic distribution, treatment patterns, and utilization trends by prescriber type (ONC and URO). This study highlights how URO are playing a pivotal role in management of post-taxane mCRPC patients receiving 177 Lu-PSMA-617. As additional data with 177 Lu-PSMA-617 becomes available, we anticipate the role of URO to significantly evolve with the potential for earlier use of 177 Lu-PSMA-617 for pre-taxane mCRPC patients.

81 Background: In March 2022, the US Food and Drug Administration approved 177Lu-PSMA-617 for the treatment of patients with prostate-specific membrane antigen (PSMA) positive metastatic castration resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition (ARPI) and taxane-based chemotherapy. This real-world study aims to describe clinical characteristics, treatment use, clinical outcomes in patients treated with 177Lu-PSMA-617 in a growing US dataset. Methods: Adults (≥18 years) with ≥1 claim for 177Lu-PSMA-617 between 3/01/22 and 6/30/2023 in the IQVIA open-source pharmacy and medical claims databases were retrospectively identified and included in this analysis. Clinical characteristics and treatment use, including prior treatment exposures, were derived from this cohort. A subset of these patients with available PSA results were assessed for PSA response after initiation of 177Lu-PSMA-617. Baseline PSA was defined as the closest PSA value within 90 days prior to or on the first 177Lu-PSMA-617 claim (index date). Post-treatment PSA response was defined as the lowest PSA value ≥28 days after the index date. The proportion of patients with ≥ 50%, ≥80% and ≥90% PSA reductions were reported. Results: A total of 1,710 patients treated with 177Lu-PSMA-617, with mean (standard deviation) age was 72.2 (8.5) years, met eligibility and were included in the study. Common comorbidities included hypertension (34.7%), osteoarthritis (27.3%) and dyslipidemia (23.9%). Based on ICD-10 codes, 1,447 (84.6%) patients had bone metastases, and 575 (33.6%) had visceral metastases, of whom 128 (7.5%) had liver metastases. Only 59 (3.5%) patients had lymph node only metastasis. In the pre-index period, 83.4% patients had used prior ARPI and/or taxane chemotherapy, and 98% patients had used other systemic therapies. In a sub-analysis of 159 (9.3%) patients with pre- and post-index PSA values available (whose clinical characteristics are comparable to the overall cohort of 1,710 patients), median PSA at baseline before initiation of 177Lu-PSMA-617 was 61 ng/ml. Among these patients, 53.5%, 29.6% and 22.6% had PSA reductions of ≥50%, ≥80% and ≥90%, respectively, while on treatment. Rate of PSA response was similar regardless of history of ARPI or taxane use. Conclusions: To our knowledge, this is the first large-scale report of real-world US patients treated with 177Lu-PSMA-617. Clinical characteristics and PSA responses observed are consistent with results from the VISION clinical trial demonstrating benefit with 177Lu-PSMA-617 treatment. Subsequent analysis with longer follow up are needed to understand the long-term outcomes associated with 177Lu-PSMA-617 in real-world US patients.

e17043 Background: Despite comprising an important part of the treatment paradigm for metastatic castration-resistant prostate cancer (mCRPC) for over a decade, real-world use of taxanes is hindered by adverse events (AEs). AEs may lead to early treatment discontinuation, which may adversely affect outcomes. The two goals of this study were to determine the proportion of mCRPC patients who discontinue taxanes early (defining the early discontinuation threshold relative to efficacy results associated with androgen receptor pathway inhibitors [ARPIs]) and to evaluate the impact of early discontinuation on clinical outcomes, AEs, and healthcare costs. Methods: This was a retrospective, observational study of adult men with mCRPC treated with an ARPI as their first-line (1L) therapy and who initiated second-line (2L) therapy with another ARPI or a taxane. The Flatiron Health electronic health record database (07/01/2012–06/30/2020) was used to estimate Kaplan-Meier overall survival (OS) curves for the taxane cohort by the number of cycles received; these were compared with patients who received ARPI at 2L. Cox regression modeling and median PFS and OS values were used to identify the number of taxane cycles needed to achieve comparable OS to ARPI. The number of taxane cycles with similar OS outcomes to ARPI was then considered the threshold for early discontinuation. In addition, the IQVIA PharMetrics Plus claims database (01/01/2013–08/31/2021) was used to estimate taxane-related AEs (based on product information) and associated healthcare costs among patients who did and did not discontinue taxanes early. Results: From Flatiron, 473 2L ARPI patients and 214 2L taxane patients were included. Similar clinical characteristics – e.g., prostate-specific antigen level, ECOG performance status, and Gleason score – were observed between the two cohorts. Overall, 2L ARPI was associated with longer median OS (15.4 vs. 13.6 months) than 2L taxane. The number of taxane cycles needed to reach comparable OS to ARPI was determined to be 8. Patients receiving >8 cycles (n=48; 22%) compared to those receiving ≤8 cycles (n=166; 78%) had longer median OS (18.4 vs. 11.9 months, respectively) and PFS (9.0 vs. 4.3 months, respectively). From PharMetrics, 158 2L taxane patients were included. Patients receiving >8 cycles (n=20; 13%) were more likely to experience an AE (95% vs. 88%) than those receiving ≤8 cycles (n=138; 87%) but had lower mean AE-related total healthcare costs per patient per month ($3,429 vs. $6,334). Conclusions: These results suggest that mCRPC patients need to receive >8 cycles of taxane at 2L to receive more clinical benefit than 2L ARPI. However, the vast majority of patients in the study discontinued taxane early, resulting in shorter survival outcomes compared to ARPI.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

64 Background: Numerous treatments with different mechanisms of action are approved for metastatic castration-resistant prostate cancer (mCRPC), but real-world studies increasingly indicate that androgen receptor pathway inhibitors (ARPIs) are the most common treatment choice at both first- (1L) and second-line (2L). Nonetheless, robust evidence on the clinical effectiveness of ARPIs when used sequentially is lacking. The aim of this study was to examine the real-world treatment patterns and associated progression-free survival (PFS) among patients with mCRPC in the United States (US). Methods: This retrospective cohort study used Flatiron Health electronic health record data from 01/01/2013 to 06/30/2020. Included patients were male, aged ≥18 years, had a confirmed diagnosis of mCRPC within the study period, and received ≥1 systemic therapy post-mCRPC diagnosis. Three treatment subgroups were examined, with ARPI defined as abiraterone or enzalutamide: all 1L ARPI users; all 2L ARPI users irrespective of 1L therapy; and 1L ARPI users who received another ARPI at 2L. Treatment patterns were evaluated descriptively; time to next therapy (TTNT) was measured from the start of the ARPI of interest to the start of the subsequent line of therapy. The Kaplan-Meier method was used to evaluate PFS from the start of the ARPI therapy of interest until progression or death from any cause. Results: The study included 2,588 patients (mean age 72 years). ARPIs were the most prescribed systemic therapy in both the 1L and 2L settings: 63% (1,634/2,588) and 46% (808/1,760), respectively. Among 1L ARPI patients, 28.9% received 2L ARPI, 14.0% 2L taxane, 14.3% 2L combo therapies, and 32% received no further therapy. The median TTNT was 7.6, 6.2, and 5.1 months for 1L ARPIs, 2L ARPIs among all users, and 2L ARPIs among patients who received 1L ARPIs, respectively. The corresponding median PFS was 6.5 months, 4.5 months, and 3.9 months, respectively. Conclusions: Among real-world mCRPC patients in the US, ARPIs remain the most common therapy at both 1L and 2L. However, sequential ARPI use appeared to provide diminishing returns, with a PFS of <4 months seen at 2L in those who had received 1L ARPIs. [Table: see text]

Background: Adverse events (e.g., pyrexia) may affect treatment patterns and adherence. This study explored pyrexia risk tolerance among melanoma patients when treatment benefit is unknown versus known. Materials & methods: US respondents with stage III (n = 100) or stage III unresectable/stage IV melanoma (n = 125) chose between hypothetical melanoma treatments, defined by reoccurrence/progression-free survival and pyrexia risk, one resembling standard-of-care and one resembling dabrafenib + trametinib. Respondents chose first when efficacy was unknown and then when efficacy was known; pyrexia risk was varied systematically to define maximum acceptable risk. Results: Maximum acceptable risk of pyrexia was statistically significantly higher when efficacy was known versus unknown in stage III patients (85 vs 34%) and stage III unresectable/stage IV patients (66 vs 57%). Conclusion: Patients accepted higher levels of pyrexia risk when they understood treatment benefit.

Abstract Background Over time, guidelines for dyslipidemia management in patients at high risk of atherosclerotic cardiovascular disease (CVD) changed with the goal of improving patient outcomes. Guidelines have been released by the European Joint Task Force in 2007, 2012 and 2016, European Society of Cardiology in 2011, 2016 and 2019, Joint British Societies in 2014, and National Institute for Health and Care Excellence in 2014. Purpose Evaluate cardiovascular risk factors, treatment patterns, and cardiovascular outcomes over time related to dyslipidemia management. Methods Ten prevalent cohorts of patients with documented CVD receiving lipid-lowering therapy (LLT) were created using Clinical Research Practice Datalink (CPRD) records as of January 1, each year from 2008 through 2017. For each cohort, we identified CVD risk factors and LLT, and estimated the 1-year composite rate of fatal and nonfatal myocardial infarction (MI), ischemic stroke (IS), or revascularization. Patient follow-up was censored at the earliest of one year, end of data, or the outcome of interest. Patients in each cohort were required to be ≥18 years old, have ≥1 years of available medical history, and have received ≥2 LLT prescriptions in the prior year. Documented CVD was defined as MI, IS, angina, revascularization, transient ischemic attack, carotid stenosis, abdominal aortic aneurysm, or peripheral arterial disease. Patients could be in multiple cohorts. Results Annual patient counts ranged from 170,501 to 179,137 through 2013 and declined to 94,418 by 2017 (due to fewer patients in the overall CPRD data). Comparing 2008, 2011 (when ESC guidelines were revised) and 2017 showed the following for CVD risk factors: mean age was 71.6, 72.3, and 72.5 years; males were 59.9%, 61.1%, and 63.1%; current smoking was 15.1%, 15.2%, and 13.9%; type 2 diabetes was 18.4%, 20.2%, and 22.4%; stage 3–5 chronic kidney disease was 22.4%, 25.1%, and 22.8%; history of MI was 22.5%, 23.9%, and 27.4%; history of IS was 5.5%, 6.6%, and 7.9%; LDL <1.8 mmol/L was 27.8%, 29.2% and 37.2%; and LDL <1.4 mmol/L was 9.9%, 10.1%, and 15.6%. In terms of treatment, high intensity statin use increased from 12.9% to 15.7% to 30.8%; atorvastatin 40–80 mg use increased from 12.9% to 15.5% to 30.5%; while simvastatin 20–40 mg use decreased from 55.4% to 58.8% to 36.7%. The 1-year cardiovascular event rate declined from 2.54 to 2.35 to 1.96 events per 100 person-years (Figure). Conclusions After 2011 in the UK, there was an increased use of high intensity statins, a greater proportion of patients with LDL levels <1.8 and <1.4 mmol/L, and lower 1-year cardiovascular event rates. While improved CVD management likely contributed to the event rate decline, less than 40% of very high-risk patients achieved an LDL <1.8 mmol/L, and the proportion with LDL <1.4 mmol/L, as recommended by the 2019 ESC guidelines, was less than 20%. Clinicians should continue their efforts to reduce LDL in these patients. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen

e22102 Background: Patients with BRAF+ metastatic melanoma (MM) have more options for treatment, including targeted therapy and immunotherapy. However, the risk of toxicities may contribute to lower treatment rates and duration. Pyrexia is a reversible adverse event commonly associated with BRAF/MEK inhibitors. However, little is known about the features, management strategies, as well as variations in pyrexia management in clinical practice. Methods: The study was conducted over two phases. Phase 1 was a qualitative study conducted with expert nurses to develop a pyrexia management questionnaire. The questionnaire was further enhanced through a pre-test with nurses to improve reliability and internal validity of the responses captured for this study. During Phase 2, a cross-sectional web-based questionnaire was administered to oncology registered nurses, nurse practitioners and physician assistants. All respondents were required to have managed pyrexia in patients with MM receiving dabrafenib+trametinib (D+T). Results: Respondents (N = 201, 57.2% academic center and 42.8% community based), on average, had 12.5 years of experience and >50% had managed more than 10 patients with BRAF-MEK inhibitor in the past 12 months. Almost all respondents (97.5%) discussed pyrexia with patients at D+T initiation. At the onset of the first episode of pyrexia in a patient, most respondents either try to keep patients on the starting dose (34.9% for D, 42.8% for T) or withhold the medication only temporarily (52.4% for D and 47.8% for T), even with a fever of 104°F. Mean time to treatment reinitiation was 1.5 days and, in more than half of the instances (52.3% for D and 51.4% for T), respondents would ask the patients to reinitiate at the starting dose. Respondents also asked patients to initiate antipyretics (87.5%) or corticosteroids (34.5%) to manage pyrexia symptoms. Even at pyrexia recurrence, respondents generally preferred keeping patients on treatment, with only 4.2% recommending permanent discontinuation. In general, respondents were very comfortable in managing pyrexia-related symptoms in their patients (mean score 7.8, 1 = very uncomfortable, 10 = very comfortable). Conclusions: In clinical practice, respondents were very comfortable in managing pyrexia. They tried to keep patients on D+T as long as possible. Experienced oncology nurses, nurse practitioners and physician assistants are able to manage pyrexia symptoms and keep patients on treatment for a longer duration to help obtain maximum clinical benefit.

Low-density lipoprotein cholesterol (LDL-C) is an important causal and modifiable risk factor for cardiovascular disease. We compared proportions of patients with controlled LDL-C levels and cardiovascular event rates in patients with a history of myocardial infarction (MI) receiving lipid-lowering therapy (LLT) in the United Kingdom from 2008 through 2017. We created 10 annual cohorts of patients with a history of MI receiving LLT, using Clinical Research Practice Datalink records. Each cohort was established as of January 1 of each year and included patients ≥18 years old, with ≥1 year of available medical history, and ≥2 LLT prescriptions in the prior year. For each cohort, we identified LLT use and serum LDL-C levels, and estimated the 1-year composite rate of fatal and nonfatal MI, ischemic stroke, or revascularization. Follow-up was censored at the earliest of one year, end of data, or the outcome of interest. Patients could be in multiple annual cohorts. From 2008 through 2017, mean age was 70.1 to 70.4 years, 68.7% to 70.9% were men, 17.7% to 21.9% had diabetes, 98.2% to 98.1% had hypertension, 23.3% to 20.3% had chronic kidney disease stage 3 or above. The proportion of patients on high-intensity statins increased from 17.1% to 46.5%. In 2008, 68.9% of patients had LDL-C ≥1.8 mmol/L and 88.5% ≥1.4 mmol/L; by 2017, these proportions went down to 58.3% and 81.3%, respectively. At the same time, the 1-year composite cardiovascular event rate declined from 3.7 to 2.8 events per 100 person-years. Despite substantial improvement, more than half of patients with a history of MI do not receive high-intensity statin therapy. Moreover, LDL-C levels in the majority of patients are above 1.4 mmol/L – the goal recommended by the 2019 European Society of Cardiology guidelines for management of dyslipidemias – showing substantial need for more intensive LLT.

Characterize treatment patterns and assess low-density lipoprotein cholesterol (LDL-C) control in patients at very high risk of cardiovascular events (CVE) receiving lipid-lowering therapy (LLT) in the United Kingdom. We identified patients registered in the Clinical Research Practice Datalink who were alive on January 1, 2017. We included patients ≥18 years old, with ≥1 year of available medical history, ≥2 prescriptions of LLT in the prior year, and with documented cardiovascular disease (CVD) (myocardial infarction (MI), ischemic stroke (IS), stable or unstable angina, revascularization, transient ischemic attack, abdominal aortic aneurysm, or peripheral arterial disease). We separately analyzed subgroups with history of MI and with recent MI (within 1 year). We also created an "other very high-risk" cohort of patients with either documented CVD but no MI or IS, or no documented CVD but with diabetes and microvascular disease, insulin use, duration of diabetes ≥10 years, or an estimated glomerular filtration rate ≤60 mL/min/1.73 m2. Among patients with documented CVD (N=94,418), 27.4% had a previous MI, of whom 11.9% experienced their MI during the previous year. 31.7% of documented CVD patients, 47.6% of MI patients, 65.5% of recent MI patients, and 25.8% of "other very high-risk" patients were receiving high-intensity statins. Fewer than 3% of studied patients received ezetimibe alone or with a statin. Most documented CVD patients had LDL-C levels above European Society of Cardiology (ESC) goals: 62.8% above 1.8 mmol/L and 84.4% above 1.4 mmol/L. These proportions were 58.3% and 81.3%, respectively, in the MI subgroup, 58.8% and 81.1% in the recent MI subgroup, and 62.3% and 86.0% in the "other very high-risk" cohort. Patients at very high risk of CVE need more intensive LDL-C lowering treatment to achieve ESC-recommended goals.

The 2013 ACC/AHA guidelines focus on statin intensity instead of LDL-C goals and suggest intensive treatment of elevated LDL-C among ASCVD patients. Duration of exposure to elevated LDL-C has been shown to increase risk of CV events demonstrating an urgency to lower uncontrolled LDL-C. The goal of

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) reduce low-density lipoprotein cholesterol (LDL-C) levels and are approved for patients with familial hypercholesterolemia or atherosclerotic cardiovascular disease who require additional LDL-C lowering.