Receiving 1L Treatment Research Articles

Evaluating transportability of overall survival estimates from US to UK populations receiving first-line treatment for advanced non-small cell lung cancer: a retrospective cohort study

ObjectivesThe objective of this study is to explore how the UK versus the USA compare in patient characteristics, treatment patterns and overall survival (OS) of patients with advanced non-small cell...

Real‐world impact of pembrolizumab availability for deficient mismatch repair metastatic colorectal cancer

AbstractBackgroundImmunotherapy has emerged as a standard treatment for deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC). Pembrolizumab became widely available as a first‐line (1L) option in Australia following the Pharmaceutical Benefits Scheme (PBS) listing in August 2021. The uptake of new treatment options can be lengthy.MethodsThe Treatment of Recurrent and Advanced Colorectal Cancer mCRC registry data at participating Australian sites was analysed from January 2015 (when MMR testing became routine). 1L treatment of dMMR cancers was compared with pre‐ and post‐PBS funding.ResultsOut of 2819 patients, 2344 (83%) had known MMR status. Of these, 162 (7%) were dMMR, which was associated with older age (median age 69 vs 63 years, P = 0.001), a right‐side primary (68% vs 31%, P < 0.001) and a BRAF V600E mutation (49% vs 11%, P < 0.001). Prior to August 2021, 85 out of 117 (73%) patients with dMMR received 1L treatment: 63 out of 85 (74%) chemotherapy and 20 out of 85 (24%) immunotherapy. Following approval, 39 out of 45 (87%) received 1L treatment and 39 out of 39 (100%) pembrolizumab. Of the patients 75 years and older, a significantly higher proportion of patients were treated with any 1L therapy post‐PBS listing (89% vs 60%, P = 0.036).ConclusionPreviously reported associations of dMMR were observed. The higher‐than‐expected proportion of patients with dMMR is likely driven by the inclusion of older patients in this real‐world study. Many patients were able to access immunotherapy prior to PBS listing, potentially through trials or access programs. Early uptake of pembrolizumab following PBS listing has been high, and this effective and well‐tolerated option has increased the proportion of elderly patients receiving active therapy.

Association between antibiotic use and mortality among older persons receiving first-line immune checkpoint inhibitors for non-small cell lung cancer (NSCLC).

e14607 Background: There is biologic plausibility that antibiotics (ABX) may reduce the effectiveness of cancer therapy, most notably immune checkpoint inhibitors (ICI). As ABX are commonly prescribed to older persons and more than a third of US persons with cancer are eligible for ICIs, use of ABX has important population health implications. We assess the association between ABX use and mortality among persons with NSCLC who receive first-line (1L) treatment. Methods: Using SEER-Medicare, we assembled a cohort of persons ≥66 years with NSCLC who received 1L treatment with platinum-based chemotherapy (PLT) or ICI (PLT without ICI, PLT with ICI, and ICI monotherapy) within one year of cancer diagnosis between 2017-2019. We assessed overall ABX exposure from 1 month to 1 year prior to treatment initiation and by ABX class. Primary outcome was all cause deaths within three years of treatment initiation or until 12/31/2020. Multivariable Cox proportional hazard models adjusting for individual-level characteristics (demographics, time-to-treatment, comorbidities, healthcare use, SEER registry, and neighborhood socioeconomic status) and landmark analyses of 1-6 months after cancer treatment were used to assess the association between ABX exposure and mortality. Results: Among 4,182 persons (mean age 75 years, 85% white, 68% chemo-immunotherapy within 2 months of NSCLC diagnosis), 63%, 18%, and 18% received PLT, PLT+ICI, and ICI, respectively. ICI+/-PLT increased in prevalence from 20% of treatments (2017) to 55% (2019). The mean age of persons who received ICI alone (78 years old) was higher than PLT or PLT+ICI. Prior to 1L treatment, 22% and 72% of persons received ABX within 30 days and 1 year prior to cancer treatment, respectively. The three most common ABX classes were fluoroquinolones (48%), penicillins (21%), and macrolides (18%). The cohort was followed for 3,274 person-years and included 2,958 deaths within 1 year and 4,144 deaths within 3 years of follow-up. Compared with persons who did not receive ABX within 3 months of cancer treatment, ABX use was associated with higher risk of death within 3 years for ICI alone [HR 1.24 (1.05-1.46) but not for PLT alone or PLT+ICI. Fluoroquinolones were associated with an elevated risk of mortality among persons who received ICI alone HR 1.41(95%CI: 1.1-1.8) and PLT alone HR 1.18 (95%CI: 1.05-1.32) but not PLT+ICI. Our findings were similar across definitions of ABX exposure (30 days to 1 year prior to treatment) and analytic landmarks after treatment initiation. Conclusions: Among patients with NSCLC who received 1L treatment, we identified an association between ABX exposure prior to treatment and increased mortality among persons who received ICI monotherapy but not PLT+ICI. As ICIs expand to more cancer types and earlier stages, ABX use may have a significant impact on outcomes and population health.

Real world impact of pembrolizumab availability for deficient mismatch repair metastatic colorectal cancer.

e15569 Background: Keynote 177 was a practice changing study, with pembrolizumab versus dealers’ choice chemotherapy +/- biologic significantly improving progression free survival in patients (pts) with previously untreated deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC). A high rate (29.4%) of pembrolizumab treated pts had stopped treatment at or before first response evaluation due to progressive disease as best response. Pembrolizumab availability in routine care is anticipated to benefit individual pts otherwise treated with chemotherapy. Additional pts not fit for chemotherapy, but fit for first line (1L) pembrolizumab, may be able to receive active treatment, which could increase the dMMR mCRC population benefit. Pembrolizumab availability may also drive increased MMR testing, which may impact the proportion of pts with dMMR mCRC. Methods: We analysed data from the TRACC registry of pts with mCRC in Australia comparing patient treatment across two cohorts. The first cohort was pts diagnosed from 1/1/2015 to 31/7/2021 when immunotherapy was only available via trial, self-funding or through a limited access program and the second cohort was pts diagnosed from 1/8/2021 to 23/1/2024, following the government’s Pharmaceutical Benefits Scheme reimbursement (PBSr) of pembrolizumab as 1L treatment for dMMR mCRC. We also examined early treatment discontinuation rates for pembrolizumab treated pts after PBSr. Results: Of 2819 mCRC pts overall, 2344 (83%) had known MMR status. Of pts tested 163 (7%) were dMMR. Pts with dMMR mCRC were older (mean age 66.6 vs 62.2, p < 0.01) and had more co-morbidities (59% vs 47% for modified Charlson Comorbidity Index ≥ 3, p < 0.01). They were also more likely to have a right side primary (67% vs 31%, p < 0.01), BRAF V600E mutation (49% vs 11%, p < 0.01) and peritoneal or brain metastases (34% vs 22%, p < 0.01). Before PBSr of pembrolizumab, 85 of 117 (73%) dMMR mCRC pts received 1L treatment; 62/85 (73%) chemotherapy, 19/85 (22%) immunotherapy and 4/85 (5%) combination BRAF inhibitor and EGFR inhibitor. Following PBSr, an increased proportion (40 of 46) of dMMR mCRC pts received any 1L treatment (87% vs 73%, p = 0.05), with 1/40 (2.5%) receiving chemotherapy and 39/40 (97.5%) pembrolizumab. In a landmark analysis of these 39 pts, 12 of 19 (63%) that had started treatment ≥ 6 months ago remained on pembrolizumab. Conclusions: A high proportion of Australian pts with mCRC are undergoing dMMR testing. Increasing testing, including of more elderly pts, may increase the proportion of mCRC pts that are dMMR compared to that reported for trial populations. dMMR mCRC pts have multiple adverse prognostic features. The broad availability of pembrolizumab, such as through the Australian PBSr, looks likely to lead to an increased proportion of pts receiving any 1L therapy. Early data suggests the expected clinical benefit, with a low rate of early treatment discontinuation.

Fruquintinib plus capecitabine versus capecitabine as first-line maintenance treatment of metastatic colorectal cancer (mCRC): Update results from the randomized, controlled, phase Ib/II study.

3567 Background: Capecitabine (Cap) is a standard first-line maintenance treatment option for colorectal cancer. Fuquinitinib (Fru) is a highly selective small molecule tyrosine kinase inhibitor that inhibits VEGFR1/2/3, which has been approved by the U.S. Food and Drug Administration (FDA) for adults with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and has recommended by NCCN guidelines as a standard treatment. Preliminary research results found that adding Fru to Cap as maintenance treatment was safe and improved progression-free survival (PFS, primary endpoint) for mCRC patients (pts). Methods: Eligible pts had been confirmed mCRC who achieved disease control (including CR/PR and SD) after at least six cycles of first-line standard chemotherapy. During phase Ib, pts received Fru (4 mg p.o. qd, 3 weeks on/1 week off, q4w]) plus Cap (850 mg/m2, p.o. bid, d1-7 and d15-21, q4w). In phase II, pts were randomized in a 1:1 ratio to receive either Fru (RP2D, 3mg, 3 weeks on/1 week off) plus Cap or Cap alone. The primary outcome was PFS 1 (defined as time from randomization to disease progression or death). Secondary were PFS 2 (defined as time from first time receiving 1L treatment to disease progression or death), ORR and DCR. Results: At data cutoff (Jan 23, 2024), 46 pts were enrolled and 38 pts who had at least one tumor assessment post treatment were randomly assigned in Fru plus Cap arm (n=20) and Cap arm (n=18). Of these pts, the median age was 59.5 (39-78) and 58.5 (32-75) years, 11 (55.0%) and 10 (55.6%) had left-sided tumors, respectively. Most pts had previously received bevacizumab therapy (65.0% /66.7%) or cetuximab (30% /22.2%). The median cycles of first-line treatment were 8 (5-12) and 8 (4-13), 8 (40.0%) and 8 (44.4%) achieved PR in the pts who had received first-line therapy, respectively. The median PFS 1 was 9.2 mo in Fru plus Cap arm and 3.1 mo in Cap arm (HR=0.385 [95% CI: 0.163 - 0.906], p=0.024). And PFS 2 was also significantly prolonged in Fru plus Cap vs Cap (16.8 vs 8.5 mo, HR=0.314 [95% CI: 0.125 - 0.788], p=0.0098). Consistently, ORR (15.0% vs 5.6%) and DCR (80% vs 55.6%) were improved in Fru plus Cap arm. The safety was similar to the previous results without new safety signals appearing. Conclusions: PFS was significantly prolonged and ORR was improved in mCRC pts treated with Fru plus Cap as first-line maintenance treatment. This trial is ongoing and updated data will be presented in the future. Clinical trial information: NCT05451719 .

Clinical Value of Timely Targeted Therapy for Patients With Advanced Non-Small Cell Lung Cancer With Actionable Driver Oncogenes.

A recent real-world study observed that 24% of patients with advanced non-small cell lung cancer (aNSCLC) with actionable driver oncogenes (ADOs) initiated nontargeted therapies before biomarker test results became available. This study assessed the clinical impact of the timing of first-line (1L) targeted therapies (TTs) in aNSCLC. This retrospective analysis of a nationwide electronic health record-derived deidentified database included patients aged ≥18 years diagnosed with aNSCLC with ADOs (ALK, BRAF, EGFR, RET, MET, ROS-1, and NTRK) from January 1, 2015, to October 18, 2022, by biomarker testing within 90 days after advanced diagnosis and received 1L treatment. Cohorts were defined by treatment patterns ≤42 days after test results: "Upfront TT" received 1L TT ≤42 days; "Switchers" initiated 1L non-TT before or after testing but switched to TT ≤42 days; and "Non-switchers" initiated non-TT before or after testing and did not switch at any time. Adjusted multivariate Cox regression evaluated real-world progression-free survival, real-world time to next treatment or death, and real-world overall survival. A total of 3540 patients met the study criteria; 78% were treated in a community setting, and 50% underwent next-generation sequencing (NGS). There was no significant difference in outcomes between Switchers and Upfront TT; inferior outcomes were observed in Non-switchers versus Upfront TT. Our findings demonstrated improved outcomes with upfront 1L TT versus non-TT in patients with aNSCLC with ADOs and observed timely switching to TT after biomarker test result had similar outcomes to Upfront TT. Opportunities remain to improve the use of NGS for early ADO identification and determination of 1L TT.

Evaluating Oncologists' Practice Patterns and Decision-Making in Locally Advanced or Metastatic Urothelial Carcinoma: The US Physician PARADIGM Study.

The treatment landscape for locally advanced/metastatic urothelial carcinoma (la/mUC) has evolved. This study examined US prescribing patterns and clinical decision-making for first-line (1L) and first-line maintenance (1LM) treatment. US-based oncologists (N = 150) completed an online survey on patient demographics, practice patterns, and important factors considered in 1L/1LM selection. Multivariable logistic regression was used to assess factors associated with more vs less frequent 1L/1LM prescribing. Physician reports estimated that 23% of patients with la/mUC had not received any systemic therapy in the previous 6 months; however, 46% received 1L, 32% received second-line, and 22% received subsequent-line systemic treatments. Of patients who were receiving 1L treatment, 72% were estimated to be receiving 1L platinum-based chemotherapy. Around 69% of patients eligible for 1LM received the treatment. Physicians categorized as frequent prescribers reported overall survival (OS), disease control rate (DCR), and rate of grade 3/4 adverse events (AEs) as factors associated with 1L treatment selection (all P < .05). OS, rate of grade 3/4 immune-mediated AEs, and inclusion in institutional guidelines were reported as attributes used in 1LM treatment selection (all P < .05). Multivariable analysis revealed OS, DCR, and rate of grade 3/4 AEs as important factors in oncologists' 1L treatment selection; academic practice setting and use of Response Evaluation Criteria in Solid Tumors version 1.1 were associated with 1LM use (all P < .05). OS and AEs were found to be relevant factors associated with offering 1L and 1LM treatment. Variability exists in physicians' decision-making in the real-world setting for la/mUC.

Treatment Patterns, Clinical Outcomes, Health Care Resource Utilization and Costs in Older Patients With Metastatic Castration-Resistant Prostate Cancer in the United States: An Analysis of SEER-Medicare Data.

Prostate cancer (PC) is more likely to develop in men ≥65 years old than in those <65 years old. This study aimed to generate real-world evidence on treatment patterns, clinical outcomes, health care resource utilization (HCRU), and costs among older patients with metastatic castration-resistant PC (mCRPC). A claims algorithm based on treatments expected for mCRPC was used to identify men ≥65 years old with mCRPC in the SEER-Medicare data between 2007 and 2019. The index date was defined as the date of the start of first-line therapy (1L). Treatment patterns and all-cause and PC-specific HCRU and costs were measured in the 12 months preindex period and the postindex follow-up period. Time to next treatment or death (TNTD) and overall survival (OS) were assessed in the follow-up period. A total of 4758 patients met the eligibility criteria and received 1L treatment. Among these 1L patients, 57.4% subsequently received second-line (2L) treatment; among patients receiving 2L treatment, 49.3% subsequently received third-line (3L) treatment. Abiraterone, enzalutamide, and docetaxel were most common regimens in 1L (41.9%, 22.0%, 22.0%, respectively), 2L (33.3%, 32.7%, 13.6%, respectively), and 3L (17.9%, 25.1%, 22.3%, respectively). On average, patients had 1.2 inpatient admissions, 1.1 emergency room visits, and 27.6 outpatient visits per year during follow-up. The mean total all-cause and PC-related costs during the follow-up period were $111,060 and $99,540 per-patient-per-year, respectively. Median TNTD was 9.3, 6.5, and 5.7 months for 1L, 2L, and 3L, respectively. Median OS from the start of 1L treatment for mCRPC was 21.5 months. Among older patients with mCRPC, high attrition from 1L to subsequent lines of therapy was observed. Median TNTD was <1 year and median OS was <2 years. These results highlight a need to introduce more effective mCRPC therapies in 1L to improve clinical outcomes for older patients.

Physicianreported treatment patterns and outcomes in metastatic bladder cancer in the USA: the CancerMPact® Survey 2020.

Aim: This study assessed physician-reported treatment patterns for metastatic bladder cancer. Materials & methods: A total of106 USA-based physicians were surveyed in 2020 using the CancerMPact® online survey. Results: Among cisplatin-eligible patients, 86.1% received first-line (1L) platinum-containing chemotherapy, most commonly cisplatin plus gemcitabine, and 9.8% received immune checkpoint inhibitor monotherapy. Among cisplatin-ineligible patients, 46.5% received 1L platinum-containing chemotherapy, most commonly carboplatin plus gemcitabine and 46.2% received 1L immune checkpoint inhibitor therapy. Approximately 44% of patients who received 1L treatment received second-line (2L) therapy after progression. Conclusion: Platinum-containing chemotherapy was the most widely reported 1L treatment approach. A high proportion of patients received no 2L therapy. Validation in an updated dataset is warranted following the practice-changing approvals of avelumab 1L maintenance and additional 2L options.

Real-world (RW) outcomes of patients (pts) with advanced breast cancer (aBC) with and without resistance alterations (alts) detected in cell-free circulating tumor DNA (ctDNA) prior to CDK4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET) treatment.

1081 Background: CDK4/6i plus ET is standard of care first-line (1L) therapy for hormone receptor positive (HR+), HER2- aBC. While molecular analyses from trials and pts have identified several mechanisms of resistance to CDK4/6i plus ET, currently, no biomarkers (outside of hormone status) are used for therapy selection. We utilized RW data to assess impact of putative baseline CDK4/6i+ET resistance alts (CDK4/6i+ET-R) on clinical outcomes among pts with aBC treated with CDK4/6i. Methods: Pts with aBC were identified via the Guardant INFORM database; those with a ctDNA test within 90 days prior to CDK4/6i start were included in this analysis. Based on previous studies, oncogenic or likely oncogenic alterations (as characterized by OncoKB) in the following genes were considered CDK4/6i+ET-R alts: RB1, PTEN, AKT1, CCNE1, ERBB2, FGFR1, FGFR2, and KRAS. Pts with &gt;1 CDK4/6i+ET-R alt were compared to pts without any CDK4/6i-R alts. Kaplan-Meier plots, log-rank tests (LR) and multivariate Cox proportional hazards models (HR) adjusted (adj) for age, sex, year of ctDNA test and line of therapy were used to assess differences in time to next treatment (TTNT) and overall survival (OS). Results: 1075 pts with aBC treated with CDK4/6i (27% receiving 1L treatment) met inclusion criteria, 293 of whom (27%) had &gt;1 alt in a CDK4/6i+ET-R gene. Pts with CDK4/6+ETi-R alts had significantly shorter TTNT (8.7 mos vs 14.2 mos, LR p=0.001; adj HR 1.36, 95%CI 1.11-1.66, adj p=0.003) and OS (28.3 mos vs 60.9 mos, LR p=&lt;0.0001; adj HR 2.19, 95%CI 1.69-2.82, adj p=&lt;0.0001) compared to those without. This divergence was more pronounced for patients receiving 1L CDK4/6i (TTNT: 10.7 mos vs 24.6 mos, LR p=0.006, adj HR 1.84, 95%CI 1.18-2.87, adj p=0.007; OS: 23.8 mos vs 67.3 mos, LR p&lt;0.0001, adj HR 3.27, 95%CI 1.89-5.62, adj p&lt;0.0001). Individual gene contributions towards less favorable TTNT are shown. Conclusions: We demonstrate via RW data that patients with &gt;1 pre-treatment ctDNA alt in a curated list of CDK4/6i+ET-R genes have significantly worse outcomes on CDK4/6i plus ET treatment, a difference more pronounced among patients receiving 1L therapy. This data is among the first successful efforts to validate a clinically useful multi-gene clinical biomarker that has the potential to predict CDK4/6i plus ET resistance. Further exploration of this signature’s prognostic and predictive utility for CDK4/6i plus ET use is ongoing to better refine personalized treatment selection in HR+/HER2- aBC. [Table: see text]

Impact of EML4-ALK fusion variant and co-occurring TP53 mutation on treatment duration of first-line next-generation ALK TKIs in ALK fusion+ NSCLC.

9029 Background: Molecular biomarkers such as EML4-ALK fusion variant 3 (V3) and TP53 mutation are associated with poor prognosis in patients (pts) with anaplastic lymphoma kinase fusion positive ( ALK+) non–small cell lung cancer (NSCLC). We evaluated the effect of EML4-ALK fusion variants and TP53 mutation status on time to treatment discontinuation (TTD) of first-line (1L) treatment with a next-generation ALK tyrosine kinase inhibitor (TKI) in pts with ALK+ NSCLC in the real-world setting. Methods: Pts with advanced/metastatic NSCLC who were ALK+ in circulating tumor DNA by Guardant360 (G360) liquid biopsy test from Jan 1, 2018, to Dec 31, 2021, and received 1L monotherapy with a next-generation ALK TKI (alectinib, brigatinib, ceritinib, lorlatinib) were identified in the Guardant INFORM clinical-genomics database. Median TTD of 1L ALK TKI treatment was determined by Kaplan-Meier (KM) methods. The impact of EML4-ALK fusion variant and TP53 mutation status on TTD was evaluated. Results: Database search identified 495 pts with advanced/metastatic NSCLC who had ALK fusion by G360; of these, 214 pts received 1L treatment with a next-generation ALK TKI; 164 had G360 testing before treatment (alectinib, n=147; brigatinib, n=7; ceritinib, n=2; lorlatinib, n=8). Among these 164 pts, median age was 58.6 y, 53% were female, and 29% had baseline brain metastases. Median follow-up from start of 1L treatment was 14.8 mo. Median TTD was 19.6 mo (95% CI: 13.6–not reached [NR]). TP53 mutations were detected in 66 pts (40%). Median (95% CI) TTD in pts with TP53 mutation vs WT was 17.1 (9.5–28.5) vs 21.9 mo (14.3–NR; log-rank P=0.1712). Of 130 pts with EML4-ALK fusion variant type detected, 63 (48%) had V1, 54 (42%) V3, 8 (6%) V2, 4 (3%) V5, and 1 (1%) V8. In pts with EML4-ALK fusion V1 vs V3, median (95% CI) TTD was 19.0 (13.6–NR) vs 21.8 mo (8.7–NR; HR: 0.73; log-rank P=0.3039), with the KM plot showing numerically longer TTD in pts with V1 vs V3 during the first 18 mo and lines crossing at the tail end. Of 117 pts with both an EML4-ALK fusion variant (V1/V3) and TP53 data, 21 (18%) had both V3 and a TP53 mutation. Pts with co-occurring EML4-ALK V3 and TP53 mutation had the shortest TTD (median TTD 8.7 [3.9–NR; HR: 2.59; P=0.0219]; Table). Conclusions: Among pts with NSCLC and ALK fusion, co-occurrence of EML4-ALK V3 and TP53 mutation is common and associated with poor prognosis and high risk of early discontinuation of 1L treatment with a next-generation ALK TKI, most likely due to disease progression. Additional novel or combination therapies are warranted for this subpopulation. [Table: see text]

Dosing patterns and treatment patterns in real-world patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who received FOLFIRINOX in the first line.

e16255 Background: While FOLFIRINOX (FFX) demonstrated a significant overall and progression-free survival benefit vs. gemcitabine in the PRODIGE 4/ACCORD 11 trial among previously untreated patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC), treatment with FFX was associated with a higher rate of grade 3/4 adverse events (AEs). In an effort to reduce toxicity, modified FFX (mFFX) regimens that employ lower doses of components of the regimen have been developed. To better understand the frequency and degree of dose modifications in practice, we examined real-world (RW) dosing patterns among mPDAC pts receiving FFX in first line (1L). Methods: This retrospective observational study utilized the Ontada Clinical Data View: Pancreatic Cancer database. Adult pts diagnosed with mPDAC between January 2015 and November 2022 who initiated treatment with FFX or mFFX within 90 days of their diagnosis for metastatic disease (1L) were included in the study. Pts were required to have an available body surface area measurement within 7 days of the index date. Doses of each FFX component were measured during cycles in which pts received all four components of the FFX regimen on the same date. mFFX was defined as administration of &lt; 150mg/m2 of irinotecan or &lt; 2,720mg/m2 5-FU total during cycle 1. Results: Of the 1,326 pts eligible meeting inclusion criteria and receiving 1L treatment with FFX or mFFX, 1,325 received mFFX and 1 received FFX. The median age at 1L initiation was 65yr (IQR: 58–70), 57% (754 pts) were male, 69% (916 pts) were white, 15% (197 pts) had an ECOG score of 0, 42% (550 pts) had an ECOG score of 1, and 78% (1028 pts) were stage IV at diagnosis. The bolus of 5-FU was frequently omitted—only 20% (262 pts) received it in the first cycle. If pts received the bolus, they did not receive the 5-FU infusion, with the exception of 1 pt. For pts receiving at least two cycles, the percentage of pts with dose reductions of ≥10% (≥20%) between the first and last cycle were 20% (11%) for the 5-FU infusion, 18% (13%) for the 5-FU bolus, 34% (21%) for irinotecan, 12% (9%) for leucovorin, and 40% (28%) for oxaliplatin. Median starting doses were 2400, 401, 152, 399, and 85 mg/m2 for the 5-FU infusion, bolus 5-FU, irinotecan, leucovorin, and oxaliplatin components, respectively. The median number of cycles was 5 (IQR: 3–10) and the median dose intensity per week was 940 mg/m2 for 5-FU, 179 mg/m2 for leucovorin, 38 mg/m2 for oxaliplatin, and 73 mg/m2 for irinotecan. Conclusions: In a RW cohort of pts with mPDAC treated with 1L FFX, almost all received a modified version of the regimen. The 5-FU bolus was omitted for most pts. Doses of other components fell over time for a notable percentage of patients, which may reflect clinician efforts to manage FFX toxicity.

Adverse events in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who received FOLFIRINOX in the first line.

e16295 Background: Quality of life is particularly important for patients (pts) with short life expectancy, such as those with metastatic pancreatic ductal adenocarcinoma (mPDAC). While first line (1L) FOLFIRINOX (FFX) is recommended by treatment guidelines for pts with mPDAC and good performance status, the regimen is known to be associated with significant toxicity that impacts quality of life. More than half of pts experience adverse (AEs)—such as nausea and vomiting, diarrhea, fatigue, neuropathy, anemia, thrombocytopenia, and neutropenia—during treatment with FFX. Efforts to reduce AEs have led to the use of modified FFX (mFFX) regimens that utilize lower doses of components of the regimen. Additional evidence on AEs associated with FFX and mFFX in the real world (RW) is needed. We assessed AEs in a RW cohort of mPDAC pts treated with FFX or mFFX in 1L. Methods: This retrospective observational study utilized the Ontada Clinical Data View: Pancreatic Cancer database. Adult pts diagnosed with mPDAC between January 2015 and November 2022 who initiated treatment with FFX or mFFX within 90 days of their diagnosis for metastatic disease (1L) were included in the study. Pts were required to have an available body surface area measurement within 7 days of the index date. mFFX was defined as administration of (i) &lt; 150mg/m2 of irinotecan, or (ii) &lt; 2,720mg/m2 5-FU total during cycle 1. Diarrhea, fatigue, nausea and vomiting, and neuropathy were available in the data as ungraded AEs abstracted from clinician notes. Assessment of hematologic and hepatic AEs were based on observed lab values and were graded according to the Common Terminology Criteria for Adverse Events version 5. Results: Of the 1,326 pts meeting study inclusion criteria and receiving 1L treatment with FFX or mFFX, 1,325 received mFFX and 1 received FFX. The median age at 1L initiation was 65yr (IQR: 58–70), 57% (754 pts) were male, 69% (916 pts) were white, 15% (197 pts) had an ECOG score of 0, 42% (550 pts) had an ECOG score of 1, and 78% (1028 pts) were stage IV at diagnosis. The median number of cycles was 5 (IQR: 3–10) and the median dose intensity per week was 940 mg/m2 for 5-FU, 179 mg/m2 for leucovorin, 38 mg/m2 for oxaliplatin, and 73 mg/m2 for irinotecan. Notable grade 3/4 AEs were: 16.4% neutropenia, 4.4% thrombocytopenia, 5.7% anemia, 4.7% elevated ALT, 4.9% elevated AST, and 10.6% elevated ALP. Of the ungraded AEs reported in clinician notes, 17.3% of pts experienced diarrhea, 10.9% fatigue, 10.9% nausea and vomiting, and 11.9% neuropathy. Conclusions: In a RW cohort of mPDAC pts treated with 1L FFX or mFFX, nearly all were treated with mFFX. The burden of serious AEs for mPDAC pts during 1L treatment with FFX or mFFX was high, with 30% (403 pts) experiencing at least one grade 3/4 AE.

Clinical value of timely targeted therapy (TT) for patients with advanced non-small cell lung cancer (aNSCLC) with actionable driver oncogenes (ADO).

6507 Background: Recent real-world studies observed that some aNSCLC pts with ADO initiated non-targeted therapy (non-TT) before biomarker test results became available. This study assesses the clinical impact of the timing of first line (1L) TT in aNSCLC pts with ADO. Methods: In a retrospective analysis of the nationwide Flatiron Health electronic health record-derived de-identified database, pts aged ≥18 years, diagnosed (Dx) with aNSCLC between 1/1/2015-10/18/2022, had ADO (ALK, BRAF, EGFR, RET, MET, ROS-1, or NTRK) based on biomarker testing ≤ 90 days of advanced Dx, and received 1L treatment (tx) were included. Cohorts were defined by tx patterns after test result: Cohort 1 received 1L TT ≤ 42 days; Cohort 2 initiated 1L non-TT before or after testing but switched to TT ≤ 42 days; Cohort 3 initiated non-TT before or after testing and did not switch to TT ≤ 42 days. Pts were followed from test results + 42 days until 11/30/2022 or death, whichever earliest. Multivariate Cox regression evaluated real-world progression-free survival (rwPFS) and overall survival (OS) between cohorts. Results: A total of 5156 aNSCLC pts with ADO were included: 79% were treated in the community setting and 56% received NGS testing. Most common ADO were EGFR and ALK for both Cohort 1 (78% and 13%) and Cohort 2 (67% and 24%); EGFR (39%) and BRAF (35%) for Cohort 3. Cohort 3 included more rare mutations (MET, NTRK, RET). Statistically significant differences were observed in gender, race/ethnicity, practice type, and area-level socioeconomic status across all cohorts. There was no significant difference in outcomes observed between Cohort 2 and 1, but significantly inferior outcomes in Cohort 3 vs 1. Conclusions: Our findings demonstrated better outcomes with upfront 1L TT vs non-TT in aNSCLC pts with ADO. The comparable outcomes between pts who received 1L TT after test result and pts who switched to TT ≤ 42 days of test result available underscore the importance of timely tx decisions based on ADO detection in lieu of tx-switch at progression. Opportunities remain to improve utilization of NGS to identify all ADO upfront to inform the appropriate 1L TT when indicated. [Table: see text]

RET testing and treatment patterns among patients with aNSCLC in US clinical practice.

9091 Background: Biomarker testing, including for rearrangement during transfection (RET), is recommended and important in selecting efficacious targeted therapy for patients with advanced non-small cell lung cancer (aNSCLC). This retrospective cohort study characterized RET testing and treatment patterns among aNSCLC patients in clinical practice. Methods: We used the nationwide Flatiron Health electronic health record-derived de-identified database to select patients diagnosed with aNSCLC (stage ≥IIIB) from 2017-2022. We measured rates of RET testing (test result ≤90 days after advanced diagnosis). We used logistic regression to identify baseline characteristics predictive of timely testing. Finally, we described treatment patterns for patients with RET+ aNSCLC before and after the US approval of RET inhibitors. Results: Among 26,329 aNSCLC patients, rates of RET testing ≤90 days after advanced diagnosis increased from 25% (2017 Q1) to 73% (2022 Q1). Patients were less likely to receive RET testing within 90 days if they were Black (multivariate odds ratio [OR] 0.8) or Hispanic (OR 0.8) compared to White, or had Medicare (OR 0.9; all p&lt;0.001) compared to commercial insurance. Patients were more likely to receive RET testing within 90 days if they were in the highest socioeconomic quintile (OR 1.4), had de novo disease (OR 2.1), or no history of smoking (OR 1.3; all p&lt;0.001). Between 2017 and 2022, there were increases in the use of next-generation sequencing (66% to 89%) and blood samples for biomarker testing (25% to 49%) and a decrease in mean days from diagnosis to test result (33 to 28) for the first RET test among those who had testing within 90 days. Among all patients with aNSCLC tested within 90 days (n=12,275), 73 were RET+ and received 1L treatment ≤90 days after advanced diagnosis. The most common 1L treatments before (n=35) and after (n=38) RET inhibitor approval were chemotherapy (40%) and RET inhibitor (42%), respectively (Table). Conclusions: RET testing has increased over time, but certain patient subgroups are less likely to receive timely RET testing and therefore may not be optimally treated. Among patients with RET+ aNSCLC identified after RET inhibitor approval, only 42% were treated with a RET inhibitor in the 1L setting. These results suggest both disparities in access to RET testing and unmet medical need among patients with RET+ aNSCLC. [Table: see text]

Patient-reported outcomes (PROs) among men receiving talazoparib (TALA) + enzalutamide (ENZA) vs placebo (PBO) + ENZA as first-line (1L) treatment for metastatic castration-resistant prostate cancer (mCRPC): Results from a phase 3 study (TALAPRO-2).

5013 Background: TALAPRO-2 (NCT03395197) showed statistically significant improvement in radiographic progression free survival with TALA + ENZA (n=402) vs PBO + ENZA (n=403) (HR=0.63 95% CI 0.51-0.78; P&lt;0.001) in men receiving 1L treatment for mCRPC. Here we report PRO endpoints from TALAPRO-2. Methods: PROs were assessed at day 1 (baseline) and at scheduled visits until radiographic progression (every 4 weeks until week 53, and then every 8 weeks) using the EORTC QLQ-C30 and its prostate cancer module, QLQ-PR25. Prespecified PRO analyses included overall mean change from baseline (per longitudinal repeated measures mixed-effects model) and time to definitive clinically meaningful (≥10-point change) deterioration (TTD). Between-arm comparisons of TTD were made using a stratified log-rank test and a Cox proportional hazards model. Results: Of the 805 men randomized and treated, 793 had a baseline score followed by at least 1 post-baseline score; TALA + ENZA (n=395), PBO + ENZA (n=398). Although the treatment effect on global health status (GHS)/quality of life (QoL) significantly favored PBO + ENZA, the predefined threshold of clinical meaningfulness was not met; moreover, no significant differences between the arms were observed in any functioning scales. A significantly longer TTD in GHS/QoL was observed for TALA + ENZA; HR=0.780 (95% CI: 0.62, 0.99), P=0.038; median: 30.8 months vs 25.0 months. A numerical greater delay in TTD in urinary symptoms was longer for TALA + ENZA; HR=0.759 (95% CI: 0.543, 1.061), P=0.105; median not reached vs 35.9 months. Additional PRO results will be presented. Conclusions: Compared with PBO + ENZA, in the TALA + ENZA arm there was 1) a modest deterioration disfavoring GHS/QoL (deterioration was not clinically meaningful based on the predefined threshold), and 2) a maintenance in all functioning scales. TTD in GHS/QoL was significantly longer with TALA + ENZA vs PBO + ENZA, reflecting improved disease control. These results complement the benefit-risk assessment of TALAPRO-2. Clinical trial information: NCT03395197 . [Table: see text]

Abstract 924: The prognostic impact of the KRAS G12C-mutation in non-small cell lung cancer (NSCLC): a real-world analysis

Abstract Background: KRAS mutations occur in ~30% of NSCLC; KRAS G12C is the most common subtype (~40%). Limited data exist on the prognostic impact of KRAS G12C in NSCLC. Methods: This retrospective study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine Clinico-Genomic Database (FH-FMI CGDB; January 1, 2011-March 31, 2022). De-identified data originated from ~280 US cancer clinics (~800 sites of care). Patients (pts) were aged ≥18 years; had advanced (adv)/metastatic NSCLC; and had received 1L treatment (tx) initiated on or after October 1, 2016. Pts with EGFR, ALK, ROS1, BRAF, MET, or NTRK alterations were excluded. Key endpoints were overall survival (OS) and real-world progression-free survival (rwPFS). Propensity score matching and a multivariate Cox hazard model were used. Results: Analyses included pts with KRAS G12C (n=847) and KRAS wild-type (WT; n=2679) NSCLC. In comparison to WT, pts with KRAS G12C were more likely to be female (56% vs 40%), former/current smokers (97% vs 93%), have non-squamous disease (91% vs 52%), have Stage IV disease at initial diagnosis (64% vs 56%), have brain metastases (22% vs 16%), have low (&amp;lt;10 mut/Mb) tumor mutational burden (59% vs 51%), and have high (≥50%) PD-L1 expression (43% vs 23%). Overall, 39% of KRAS G12C, and 33% of WT received chemo (CT) + immunotherapy (IO) as 1L tx. More pts with KRAS G12C vs WT did not receive 2L tx (61% vs 54%). No significant differences were seen in rwPFS and OS between KRAS G12C and WT (Table 1). In pts receiving 1L CT + IO (n=1218), pts with KRAS G12C had shorter rwPFS compared with pts with WT (adjusted hazard ratio: 1.22; p=0.04). In pts with KEAP1 or STK11 mutations, co-mutation with KRAS G12C was associated with shorter OS. Conclusions: Pts with KRAS G12C and WT had similar overall prognosis; however, those with KRAS G12C had worse rwPFS with CT + IO tx, as opposed to a trend in the opposite direction for pts treated with IO mono. KRAS G12C imposed worse prognosis vs WT in pts with STK11 or KEAP1 mutations. Table 1. OS and rwPFS in the overall population and subgroups PSM-based comparisona KRAS G12C KRAS WT OS N 847b 1318b Median, months (95% Cl) 11.8 (10.2-14.1) 12.5 (11.6-14.0) HR (95% CI); p value 1.05 (0.91-1.21); 0.47 rwPFS N 846b,c 1317b,c Median, months (95% Cl) 5.5 (4.9-6.2) 5.6 (5.2-5.9) HR (95% CI); p value 1.06 (0.94-1.20); 0.33 Multivariate Cox proportional hazard modela Multivariate HRd (95% CI), KRAS G12C vs KRAS WT; p value OS All pts (N=3526) 1.05 (0.92-1.10); 0.47 KEAP1 mutation (n=506) 1.64 (1.17-2.00); &amp;lt;0.01 STK11 mutation (n=523) 1.38 (1.02-1.86); 0.04 IO monotherapy in 1L (n=752) 0.86 (0.64-1.15); 0.32 CT + IO in 1L (n=1218) 1.15 (0.92-1.44); 0.22 rwPFS All pts (N=3526) 1.06 (0.94-1.20); 0.35 KEAP1 mutation (n=506) 1.51 (1.11-2.05); &amp;lt;0.01 STK11 mutation (n=523) 1.25 (0.97-1.61); 0.09 IO monotherapy in 1L (n=752) 0.91 (0.71-1.17); 0.46 CT + IO in 1L (n=1218) 1.22 (1.01-1.49); 0.04 aRisk factors included in PSM and the multivariate Cox model: age, gender, race, ECOG performance status, smoking status, histology, stage at initial diagnosis, presence of brain metastases, PD-L1 expression category, and 1L treatment; bAll pts in KRAS G12C and WT populations in PSM (1 to up to 2 match); cAll patients with atleast 1 progression assessment; dMultivariate Cox model HR was based on complete case analyses, i.e., pts with non-missing data. CI, confidence interval; HR, hazard ratio; PSM, propensity score matching. Citation Format: Lova Sun, Julia Kim, Shetal A. Patel, Yehrim Kang, Vincent Pretre, Nydia Caro, Stefanie Knoll, Rafael Caparica, Fen Ye, Karen L. Reckamp. The prognostic impact of the KRAS G12C-mutation in non-small cell lung cancer (NSCLC): a real-world analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 924.

Abstract P4-01-21: Phase 2 Study of the CDK4/6 Inhibitor FCN-437c in Combination With Fulvestrant or Letrozole and Goserelin in Patients With HR+, HER2– Advanced Breast Cancer

Abstract Background: FCN-437c is a second-generation CDK4/6 inhibitor. Phase 1b clinical results indicated improved antitumor activity in patients (pts) with HR+, HER2– advanced breast cancer (ABC), treated with FCN-437c + letrozole. Methods: This Phase 2, multicenter, open-label clinical study evaluated the antitumor activity, pharmacokinetics (PK), and safety of FCN-437c + fulvestrant in post-menopausal pts (Cohort 1, treatment-naïve or 2L), FCN-437c + letrozole + goserelin in pre-menopausal pts (Cohort 2, treatment-naïve). Pts received FCN-437c (200 mg QD) in a 21-day-on and 7-day-off schedule either in combination with fulvestrant (500 mg D1) or letrozole (2.5 mg QD) + goserelin (3.6 mg once per cycle) in 28-day cycles. The primary endpoint was overall response rate (ORR) and secondary endpoints were progression-free survival (PFS), overall survival (OS), PK, and safety. Results: At study cutoff (Feb 7, 2022), 36 pts were enrolled in Cohort 1 and 31 pts were in Cohort 2; 42 (62.7%) pts had visceral metastases and 9 (13.4%) pts had bone-only metastases. In Cohort 1, 18 pts were treatment-naïve, 15 pts had received 1L treatment, and 3 pts had received ≥2L treatment. In Cohort 2, 25 pts were treatment-naïve and 6 pts had received 1L treatment. Overall, 27 pts in the per-protocol set achieved partial response (PR), resulting in an ORR of 40.9% (95% CI, 29.0-53.7). Median follow-up was 12.8 months, and median PFS (mPFS), OS, and DOR were not reached. However, at 12 months, the PFS rate was 67.7% (95% CI, 53.2-78.6) and the OS rate was 95.9% (95% CI, 84.5-99.0); the 6-month DOR rate was 96.0% (95% CI, 74.8-99.4). In Cohort 1 (n=35), 11 pts achieved PR: the ORR was 31.4% (16.9-49.3%) and mPFS was 12.9 months (95% CI, 9.2-NR); the 6-month DOR rate was 100%. In Cohort 2 (n=31), 16 pts achieved PR: the ORR was 51.6% (95% CI, 33.1-69.9%). mPFS, OS, and DOR were not reached; the 6-month DOR rate was 92.9% (95% CI, 59.08-98.96) (Table). Treatment-emergent adverse events (TEAEs) were observed in all pts. Majority of AE were G1 or 2 except for hematological TEAE. 58 (86.6%) pts reported grade ≥3 TEAEs, mainly neutropenia (74.6%), leukopenia (49.3%), hypertriglyceridemia (6.0%), lymphocyte count decrease (4.5%), and γ-glutamyltransferase increase (3.0%): most were reversed through dose interruption and symptomatic therapy. Steady-state PK parameters were analyzed after 15-21 days of QD administration: Cohort 1: median Tmax was 3 h, geomean T1/2 was 44.6 h, geomean Cmax was 1650.7 ng/mL, and geomean AUC0-24h was 29,148.08 h*ng/mL; the geomean accumulation ratios of AUC0-24h and RCmax were 2.18 and 1.74, respectively, compared with first dose. Cohort 2: median Tmax was 4 h, geomean T1/2 was 35.7 h, geomean Cmax was 1314.34 ng/mL, and geomean AUC0-24h was 22,889.96 h*ng/mL; the geomean accumulation ratios of AUC0-24h and RCmax were 1.95 and 1.63, respectively, compared with first dose. Conclusion: FCN-437c in combination with fulvestrant or letrozole + goserelin demonstrates antitumor activity and safety and is well tolerated in pts with HR+, HER2– ABC. This combination therapy will be further investigated in 2 ongoing Phase 3 trials (NCT05438810 and NCT05439499). Clinical trial number: NCT05004142. Research Sponsor: Avanc Pharmaceutical Co., Ltd Table. Clinical outcomes for patients in the per-protocol set. Citation Format: JiaJie Shi, Wei Li, Zhongsheng Tong, Aimin Zang, Xiaohua Zeng, Shui Wang, Tao Huang, Ying Wang, Yanqiu Song, Lihua Kang, Zheng Lv, Yehui Shi, Hua Yang, Jing Wu, Yongmei Yin, Yan Liang, Jie Tan, Jie Ming, Yaping Yang, Simin Luo, Xiujuan Gui, Ai-Min Hui, Zhuli Wu, Ling Tian, Yuchen Yang, Lei Diao, Wenjing Zhang, Yongjiao Zhang, Yunjiang Liu. Phase 2 Study of the CDK4/6 Inhibitor FCN-437c in Combination With Fulvestrant or Letrozole and Goserelin in Patients With HR+, HER2– Advanced Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-21.

Abstract P3-02-05: Interim Analysis Results from a European Disease Registry Study Aimed to Prospectively Observe Treatment Patterns and Outcomes in Patients with HER2+ Unresectable Locally Advanced or Metastatic Breast Cancer

Abstract BACKGROUND: Metastatic breast cancer (MBC) is incurable, with the primary goal of treatment being to extend survival while preserving quality of life. Treatment options available to patients (pts) with human epidermal growth factor receptor-2 positive breast cancer (HER2+ BC) may vary between countries, in terms of both the drugs used and the sequence in which they are used. There is limited data available on the clinical characteristics and outcomes in pts with unresectable locally advanced (LA) BC. This study aimed to capture real-world data on treatment patterns and clinical outcomes in HER2+ unresectable LABC and MBC. METHODS: SAMANTHA (NCT02913456) is an ongoing, prospective, multicentre non-interventional study designed to observe pts with HER2+ unresectable LABC or MBC for a period of up to 8 years on study. The primary objectives are progression-free survival (PFS), assessed according to standard medical practice, and the treatment received. Secondary objectives included overall survival (OS), duration of response and safety. This pre-planned interim analysis reports baseline characteristics, treatment regimens received, first-line (1L) PFS by advanced BC status and the incidence of adverse events (AEs). RESULTS: The study enrolled 647 pts from five European (EU) countries (Nov 2016-Nov 2019); 629 received 1L treatment and were included in data analysis. At data cut-off date (16 Nov 2021), median follow-up on study was 30.4 months (mo; range: 0.1; 60.0); 342 (54%) pts discontinued 1L treatments, of whom 170 (50%) pts received 2L treatments, 74 pts died, 49 pts were lost to follow-up, 35 pts withdrew consent and 14 pts withdrew due to physician decision. The full analysis set (FAS) included 222 (35%) LABC pts and 407 (65%) MBC pts [Table]. Pertuzumab/trastuzumab based regimens were given as 1L in the majority of pts [462 (73 %)]. The FAS Median (m) PFS in 1L was 41.3 mo (95% CI: 36.1, 54.1) for LABC and 23.5 mo (95% CI: 20.6, 27.6) for MBC. Median OS was not reached. In the FAS, any AEs were reported in 352 (56%) pts; of these 212 (34%) had a grade 3 or higher AE. Serious (S) AEs were reported in 135 (22%) pts; of whom, 36 (6%) pts had treatment related SAEs. CONCLUSIONS: This interim analysis of SAMANTHA provides a snapshot of LABC/MBC treatment practices in five EU countries, where pertuzumab/trastuzumab based regimens appear to be the most used 1L treatment options, which aligns with the recommended standard of care. The mPFS is consistent with previous literature although higher than what was reported in the pivotal clinical trial CLEOPATRA. Given the good outcome observed in 1L and the current follow-up period of 30.4 mo, the data are not yet mature enough to provide complete insights into the treatment sequencing patterns and the clinical outcomes associated with these treatments. Acknowledgments: The study is sponsored by F. Hoffmann-La Roche Ltd. Table: Demographics and baseline disease characteristics of patients by status of advanced BC Citation Format: Marija Balic, Luis Costa, Joseline Ojaimi, Cristina Marinela Oprean, José L. Passos Coelho, Isabel Pazos, Fabio Puglisi, Thibaut Sanglier, Giuseppa Scandurra, Michael Schenker, Laurentia A. Wahyudi, Georgi Zhbantov, Constanta Timcheva. Interim Analysis Results from a European Disease Registry Study Aimed to Prospectively Observe Treatment Patterns and Outcomes in Patients with HER2+ Unresectable Locally Advanced or Metastatic Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-02-05.

Real world (rw) homologous recombination repair (HRR) gene mutation testing trends in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) in the United States (US).

98 Background: Previous research suggests that HRR mutations may have prognostic value in mCRPC. Additionally, HRR mutations are therapeutically relevant and can inform treatment decisions. Limited information is available on HRR mutation testing rates in the US. This study assessed rw HRR testing patterns in pts with mCRPC in the US and described characteristics associated with HRR testing. Methods: Retrospective data from pts with mCRPC initiating first line (1L) treatment between 2014 – 2021 was obtained from the nationwide Flatiron Health electronic health record-derived de-identified database. Pt demographic and clinical characteristics were summarized descriptively across subgroups by HRR gene testing status (tested vs not tested). A multivariable logistic regression model was used to assess factors associated with receiving HRR testing, and included covariates for demographic, clinical, and treatment characteristics. Results: A total of n=8,166 pts with mCRPC receiving 1L treatment were identified. The mean age of the cohort was 72.9 (standard deviation (SD) 8.1) years. Overall, 2,122/8,166 (26%) were known to have received HRR mutation testing. Pts who did not receive HRR testing were older compared to HRR tested pts (mean age 73.7 (SD 8.5) vs 70.6 (SD 7.5) years). A higher proportion of HRR tested were receiving treatments from an academic medical center vs community practice (14.5% vs. 7.7%). Multivariable logistic regression indicated age &gt; 65 (vs &lt; 65 years), Black race (vs White), being treated in the community (vs academic), and having de novo metastatic disease (vs recurrent) were associated with a statistically significant lower odds of HRR mutation testing. In contrast, a higher socioeconomic status and being diagnosed with mCRPC after 2018 were associated with a statistically significant increased odds of HRR mutation testing. Conclusions: In this rw study, a minority of US pts with mCRPC received HRR mutation testing. Disparities in HRR mutation testing exist, and focused efforts to increase HRR testing should be developed, especially among Black pts, pts with lower socioeconomic status, pts treated in the community setting, and pts &gt; 65 years of age. [Table: see text]