Jiang, Changchuan

TPS5130 Background: Patients with prostate cancer and deleterious HRRa have poorer prognosis but derive benefit from poly (ADP-ribose) polymerase (PARP) inhibition. However, prevalence of HRRa and response to PARP inhibition are less well defined in racial/ethnic minorities. We designed the HARMONY trial to evaluate the efficacy of N/AA/P in HL and NHB patients with mHSPC and deleterious HRRa. Methods: This multicenter, open label, phase II study is open through the Hoosier Cancer Research Network in the United States. The trial enrolls patients who self-identify as HL or NHB and have mHSPC with HRRa including BRCA 1/2, BRIP1, CHEK2, FANCA, PALB2, RAD51B, and/or RAD54L. Eligible patients will have hormone sensitive, treatment naïve or minimally treated prostate cancer (i.e., bicalutamide ≤ 45 days, androgen deprivation therapy [ADT] ± AA plus P ≤ 45 days allowed). Prostate cancer variants, other therapy in mHSPC setting, or symptomatic brain metastases are exclusionary. Enrolled patients will receive 24 weeks (w) of ADT plus N/AA dual action tablet (DAT) plus P, followed by an adaptive approach based on prostate specific antigen (PSA) response. Subjects in Arm A (PSA > 4.0 ng/mL at 24 w) can continue ADT/N/AA/P for max 2 years or stop N and escalate therapy to ADT/AA/P plus 6 cycles of docetaxel followed by standard of care (SOC) therapy. Subjects in Arm B (PSA ≤ 4.0 ng/mL at 24 w) will continue ADT/N/AA/P for a total of 12 months. At 12 months in Arm B, subjects with PSA ≥ 0.2 ng/mL will continue ADT/N/AA/P for max 2 years, and subjects achieving PSA < 0.2 ng/mL have the option to continue ADT/N/AA/P for max 2 years or discontinue all therapy with the option to start SOC treatment at disease progression. PSA decline to < 0.2 ng/mL at 24w (primary endpoint) will be evaluated for each racial/ethnicity group against a historic rate of 50%. Thirty patients per racial/ethnic cohort will give 80% power at 0.1 significance to determine noninferiority with a no-inferiority margin of 0.185. Estimating 5% drop out, 64 patients will be enrolled (n=32 HL and n=32 NHB). Key secondary/exploratory endpoints include PSA reduction ≥ 90%, overall response rate, PSA/radiographic progression free survival, overall survival, time to subsequent anti-cancer therapy, quality of life and safety. Key genomic correlatives will be evaluated. ClinicalTrials.gov: NCT06392841. Study support of drug and funding: Janssen Scientific Affairs LLC. Clinical trial information: NCT06392841 .

9009 Background: International Medical Graduates (IMGs) are a vital component of the US oncology workforce, representing nearly half of practicing medical oncologists. However, systemic barriers may influence their career trajectories differently. Understanding these challenges is essential for addressing workforce disparities and optimizing cancer care delivery across diverse geographic regions. Methods: We conducted a cross-sectional study of 13,497 medical oncologists using the 2024 Dec CMS Provider Dataset linked with the 2023 Rural-Urban Continuum Codes (RUCC). Medical oncologists were identified by their self-reported primary specialties, including Hematology/Oncology, Medical Oncology, and Hematopoietic Cell Transplant. Physicians were categorized by graduation origin (based on their self-reported medical school), career stage (early: 0–10 years, mid: 11–30 years, late: >30 years post-medical school graduation). The primary outcomes included practice at Main Campus of NCI Designated Cancer Centers (as an indicator of academic practice) and the geographical location of their practice (Metro, Non-Metro, Mixed). We employed chi-squared tests for statistical comparisons and performed stratified analyses by career stage to evaluate transition patterns over time. Results: 6920 IMGs constituted 48.7% of the oncology workforce, with similar gender distributions between IMG and non-IMG oncologists (37.9% vs 36.5% female, p=0.068). Notably, early career oncologists were less likely to be IMGs (IMG vs non-IMGs: 8.2% vs 12.5%, p<0.001). Compared to Non-IMGs, IMG oncologists are less likely to practice at main campuses of NCI Center (19.9% vs. 27.7%, p<0.001), especially as their career advances (all p<0.01). (Table). IMGs had higher representation in non-metropolitan areas than non-IMGs (11.4% vs 9.1%, p<0.001), particularly in late-career stages (14.7% vs 12.3%, p=0.033), indicating their unique role in serving underserved regions. (Table). Conclusions: Our findings reveal that, IMGs are less likely to practice at main campuses of NCI-Cancer Center than their non-IMG colleagues. Meanwhile, IMG oncologists are disproportionately serving rural communities. Supporting IMG pathways in oncology is critical to ensure a balanced cancer care delivery across the United States. Practice setting distribution and academic affiliation among international medical graduates (IMGs) and US graduates (USGs) by career stage. IMG (N=6,577) Non-IMG (N=6,920) IMG (N=6,577) Non-IMG (N=6,920) NCI Center Other NCI Center Other Metro Non-Metro/Mixed Metro Non-Metro/Mixed Total 19.9% 80.1% 27.7% 72.3% 88.6% 11.4% 90.9% 9.1% Career Stage Early (0-10y) 29.1% 70.9% 36.1% 63.9% 91.1% 8.9% 95.4% 4.6% Mid (11-30y) 21.3% 78.7% 28.8% 71.2% 90.1% 9.9% 91.6% 8.4% Senior (30+y) 15.0% 85.0% 22.0% 78.0% 85.3% 14.7% 87.7% 12.3%

Background: Hormone receptor (HR)–negative, HER2-positive (also called HER2-enriched) breast cancer has no worse prognosis than other breast cancers if it is treated with HER2-targeted therapy. Medicaid expansion under the Affordable Care Act (ACA) has been shown to be associated with improved access to care and outcomes for many cancers, but its association with receipt of care for HR-negative, HER2-positive breast cancer is unknown. We examined the association of Medicaid expansion with receipt of guideline-concordant treatment, time to treatment initiation, and survival among nonelderly women newly diagnosed with HR-negative, HER2-positive breast cancer. Patients and Methods: Women aged 18 to 62 years newly diagnosed with HR-negative, HER2-positive breast cancer between 2010 and 2018 were identified from the National Cancer Database. Outcomes included receipt of stage-based guideline-concordant treatment, timely initiation of treatment (<30 days, <60 days, <90 days from diagnosis), and stage-specific 2-year overall survival. A difference-in-differences (DID) analytic approach compared outcome changes following Medicaid expansion in expansion versus nonexpansion states. Multivariable linear probability models were used to estimate treatment outcomes, and flexible parametric survival models were used to evaluate survival, adjusting for sociodemographic and clinical confounders. Results: A total of 31,401 patients were included. Medicaid expansion was associated with an increase of 0.58 percentage points (ppt; 95% CI, 0.01–1.16) in receipt of guideline-concordant treatment overall, a 2.43-ppt (95% CI, 0.68–4.18) increase in initiating guideline-concordant treatment <60 days after diagnosis, and a 1.17-ppt (95% CI, 0.02–2.32) increase in 2-year survival rate. The increase in 2-year survival associated with Medicaid expansion was most prominent for patients with stage III disease (DID, 3.81; 95% CI, 0.82–6.80). Conclusions: Medicaid expansion was associated with improved care and survival for patients with HR-negative, HER2-positive breast cancer, an aggressive cancer type for which prognosis largely depends on access to effective treatment.

8555 Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung cancer (NSCLC), with historically poor outcome. Excellent response of metastatic PSC to immunotherapy was previously reported, but its outcome compared with other NSCLCs is unknown in the immunotherapy era. Methods: NCDB was queried for stage IV NSCLC diagnosed from 2016 to 2020. Patients who were treated with chemotherapy only or immunotherapy only in the first course of treatment were included. Log-rank was used for survival analysis and adjusted by cox regression for age, gender, race, academic/integrated center, insurance, and comorbidity. Results: A total of 37,617 patients were identified, including 201 PSCs and 37,416 other NSCLCs. Pleomorphic (54%) was the most common PSC subtype. There was significant interaction between the survival effect of treatment and histology (interaction p = 0.024). When treated with immunotherapy alone, no significant difference was found between PSC and other NSCLCs (median survival 11.4 vs 12.4 months, logrank p = 0.56, HR 1.02, 95% CI 0.81 – 1.30). However, when treated with chemotherapy alone, PSC remained significantly associated with worse survival (median survival 4.5 vs. 8.5 months, logrank p <0.001, HR 0.67, 95% CI 0.54 – 0.83). Among PSC subtypes, spindle/giant cell PSCs were more likely to benefit from immunotherapy alone than pleomorphic PSCs (interaction p = 0.005), when compared with chemotherapy (Spindle/giant cell subtype: HR 0.24, 95% CI 0.14 – 0.42; Pleomorphic subtype: HR 0.60, 95% CI 0.37 – 0.99). Conclusions: Compared with other NSCLCs, PSC may not be associated with worse survival when treated with immunotherapy alone as it was when treated with chemotherapy. Distinct PSC subtypes may respond differently to immunotherapy and warrants further research. [Table: see text]

6539 Background: HER2-enriched breast cancer (estrogen and progesterone receptors negative and HER2-positive) has no worse prognosis than other breast cancers if it is treated with HER2-targeted therapy. Medicaid expansion under the Affordable Care Act (ACA) has been shown to be associated with improved access to care and outcomes for many cancers, but its impact on care for HER2-enriched breast cancer is unknown. To fill this gap, we examined the association of Medicaid expansion with receipt of guideline-concordant treatment, time to treatment, and survival among newly diagnosed nonelderly women with HER2-enriched breast cancer. Methods: Women aged 18-62 years newly diagnosed with HER2-enriched breast cancer between 2010 and 2018 were identified from the National Cancer Database. Our primary outcomes included receipt of stage-based guideline-concordant treatment, initiation of treatment <60 days, and stage-specific 2-year overall survival. A difference-in-differences (DD) approach compared outcome changes following the expansion in Medicaid expansion vs. non-expansion states. A linear probability model estimated treatment outcome, and a flexible parametric survival model evaluated survival. All models were clustered at the state level and adjusted for age group, race/ethnicity, rurality of residence, zip code-level income, comorbidity, and diagnosis year. Results: A total of 31,354 patients with HER2-enriched breast cancer were included, including 19,255 in expansion states and 12,099 in non-expansion states. Compared to patients in expansion states, patients in non-expansion states were more likely to be racial/ethnic minorities, uninsured, and diagnosed at late-stage. Medicaid expansion was not significantly associated with changes in receipt of surgery for stage I-III disease but was associated with an increase of 4.42 percentage points (ppt, 95% CI: 0.09, 8.74) in receipt of chemotherapy/targeted therapy for stage IV disease, with an increase from 90.4% pre-expansion to 92.8% post-expansion in expansion states and a decrease from 93.7% to 91.9% in non-expansion states. Medicaid expansion was also significantly associated with a 2.41 ppt increase in initiating guideline-concordant treatment within 60 days (95% CI: 0.66, 4.17; 83.5% to 82.5% in expansion states vs. 86.6% to 83.7% in non-expansion states), and a 1.18 ppt increase in two-year survival rate (95% CI: 0.03, 2.33; 94.0% to 94.9% in expansion states vs. 94.3% to 94.1% in non-expansion states). The increase in two-year survival associated with Medicaid expansion was most prominent for stage III patients (DD=3.63 ppt; 95% CI: 0.64, 6.62). Conclusions: Medicaid expansion was associated with increased receipt of timely treatment and improved 2-year survival among nonelderly women newly diagnosed with HER2-enriched breast cancer.

Abstract Aims This observational study characterized cardiovascular disease (CVD) mortality risk for multiple cancer sites, with respect to the following: (i) continuous calendar year, (ii) age at diagnosis, and (iii) follow-up time after diagnosis. Methods and results The Surveillance, Epidemiology, and End Results program was used to compare the US general population to 3 234 256 US cancer survivors (1973–2012). Standardized mortality ratios (SMRs) were calculated using coded cause of death from CVDs (heart disease, hypertension, cerebrovascular disease, atherosclerosis, and aortic aneurysm/dissection). Analyses were adjusted by age, race, and sex. Among 28 cancer types, 1 228 328 patients (38.0%) died from cancer and 365 689 patients (11.3%) died from CVDs. Among CVDs, 76.3% of deaths were due to heart disease. In eight cancer sites, CVD mortality risk surpassed index-cancer mortality risk in at least one calendar year. Cardiovascular disease mortality risk was highest in survivors diagnosed at &lt;35 years of age. Further, CVD mortality risk is highest (SMR 3.93, 95% confidence interval 3.89–3.97) within the first year after cancer diagnosis, and CVD mortality risk remains elevated throughout follow-up compared to the general population. Conclusion The majority of deaths from CVD occur in patients diagnosed with breast, prostate, or bladder cancer. We observed that from the point of cancer diagnosis forward into survivorship cancer patients (all sites) are at elevated risk of dying from CVDs compared to the general US population. In endometrial cancer, the first year after diagnosis poses a very high risk of dying from CVDs, supporting early involvement of cardiologists in such patients.