Citations

e13828 Background: Disparities in cancer outcomes between rural and urban populations are often linked to limited healthcare resources in rural areas. However, the impact of socioeconomic factors, particularly income inequality, requires further investigation. Methods: We analyzed cancer mortality rates using the Surveillance, Epidemiology, and End Results (SEER) database, focusing on rural-urban continuum codes and median county income, the proportions of patients with de novo metastatic disease at diagnosis, those aged 80 and older, and those experiencing a treatment delay of three months or more. Results: Our findings indicate that non-metropolitan counties (56.7%, 95% CI: 56.6%, 56.8%) and those with lower median incomes (54.9%, 95% CI: 54.8%, 55.1%) have significantly lower cancer survival rates than metropolitan counties (62.6%, 95% CI: 62.5%, 62.6%) and higher-income rural counties (62.6%, 95% CI: 62.6%, 62.7%), a trend consistent over the observation period. Higher proportions of de novo metastatic disease and increased treatment delays were observed in counties with lower income and greater rurality, with these counties also demonstrating higher annual percentage rates of change for both de novo metastatic disease (P < 0.05) and treatment delays (P < 0.05). Conclusions: Lower county-level median household income is associated with higher cancer mortality rates, increased de novo metastatic disease, and longer treatment delays. These results underscore the need to appreciate the role of income disparities in cancer outcomes and to improve access to oncology care in underserved rural populations.

e13809 Background: Endometrial cancer significantly impacts the Appalachian population compared to the overall United States population. Evidence supports that this difference may be due to health disparities, which includes access to affordable healthy food, obesity, and metabolic syndromes in addition to care disparities. Methods: We queried the Kentucky Cancer Registry’s online public Cancer Incidence and Mortality Registry to determine changes in age adjusted invasive corpus uteri cancer incidence and mortality rates in Appalachian (AK) and Non-Appalachian Kentucky (NAK) counties over time. Incidence rate ratios were used to analyze the difference in endometrial cancer incidence and mortality between AK and NAK populations across several time periods. The z-test for two population proportions was used to analyze differences in incidence and mortality between AK and NAK. Results: Incidence of endometrial cancer was higher in AK vs. NAK at the beginning (P < 0.002) and end (P < 0.001) of the period examined, although there was no statistically significant difference in mortality between AK vs NAK. Incidence and mortality increased in both AK (P < 0.01) and NAK (P < 0.001) across the period studied. Conclusions: Incidence in endometrial cancer in Appalachian Kentucky was significantly higher than non-Appalachian Kentucky, although mortality was not higher in the final years studied. Lower socioeconomic status, access to affordable nutritious foods, and health likely contributed to an increased incidence of endometrial cancer. With an increase in chronic diseases such as obesity prevailing in AK, there is increased exposure to unopposed estrogen, which increases the risk for developing endometrial cancer and may be reflected in these results. Education and lack of access to healthcare also are contributing factors. Although the cancer care disparities seen in Appalachia are commonly viewed as byproducts of the region’s unique culture, they can also be viewed as local expression of challenges in global oncology facing resource poor, rural regions around the world. Efforts to reduce the risk in Appalachia will require addressing the underlying problems seen in other communities worldwide with rising endometrial cancer incidence – poverty, health literacy, obesity, rising rates of diabetes, exercise and environmental pollution. Year Incidence AK (/100,000) Incidence NAK (/100,000) % Higher Incidence AK Mortality AK (/100,000) Mortality NAK (/100,000) % Higher Mortality AK 2001-2005 25.3 21.0 20.5% 1.6 1.6 0.0% 2006-2010 27.2 22.1 23.1% 1.5 1.6 -6.3% 2011-2015 30.3 24.7 22.7% 2.0 1.7 17.6% 2016-2020 31.8 26.0 22.3% 2.5 2.6 -3.8%

e13808 Background: Cancer is a leading cause of death for Latinos. They experience higher rates than their white peers of preventable, infectious-agent-causing-cancers, such as stomach & liver cancer. Latina women have experienced a 1% rise in cancer cases since 2011 & Latino children & adolescents experience higher rates of leukemia than any other racial/ethnic group. Latinos face disparities in access to healthcare, cancer screening & treatment, medical representation & experience lower rates of survival due to late-stage cancer diagnosis. Methods: To combat these inequities & identify equitable interventions for Latino health, the Institute of Health Promotion Research & the Mays Cancer Center established the Advancing the Science of Cancer in Latinos (ASCL) Conference. The fourth ASCL Conference convened in San Antonio, TX from February 21-23, 2024. The conference objectives were 1) Examine the intersection of health equity & biological underpinnings in cancer control, prevention, and treatment 2) Foster collaborative initiatives among attendees aimed at addressing cancer-related health disparities within the Latino community. The conference hosted 286 participants (speakers, researchers, physicians, healthcare professionals, patient advocates & students). It comprised of 23 sessions (3 keynotes, 6 plenaries, 6 breakouts, 3 general sessions, 1 special session, 1 lunch panel session) featuring insights from 51 speakers, a poster session highlighting 80 research abstracts & a rapid-fire session tailored for early-career investigators. Sessions focused on multiple topics relevant to Latino cancer research, clinical trials, survivorship, patient advocacy, climate change impacts on cancer, precision medicine, health policy & social determinants of health. Results: A post-conference survey from a cohort of 48 respondents underscored high levels of satisfaction, with 90% expressing contentment regarding the conference experience. Nearly all respondents (98%) rated the relevance of conference content to Latino cancer science as excellent, with 93% regarding the conference as an exceptional platform for information exchange. Impressions regarding session quality were positive, with 90% of respondents indicating a high level of satisfaction, & all survey respondents acknowledging the objectivity, balance & absence of commercial bias in the session content. Conclusions: Results showed that the resounding positivity in attendee feedback reflects the conference's success in fostering meaningful engagement among attendees. The ASCL conference facilitated an understanding of cultural nuances and barriers specific to the Latino community, stimulating collaborative efforts aimed at enhancing Latino health outcomes. Overall, this analysis affirms the conference's success in achieving its stipulated objectives and underscores the need of having consistently coordinated research endeavors to reduce Latino health disparities.

Patients receiving opioid analgesics may experience constipation [ie, opioid-induced constipation (OIC)], require treatment to induce laxation, and may be at risk for gastrointestinal perforation, an uncommon but potentially life-threatening condition. Management of OIC includes treatment with over-the-counter laxatives and peripherally acting μ-opioid receptor antagonists (PAMORAs; methylnaltrexone, naloxegol, naldemedine). In patients receiving treatment for OIC, gastrointestinal perforation may result from the laxation process, causing disruption of the gastrointestinal lining that may already have compromised integrity. A PubMed literature review and a search of the US Food and Drug Administration Adverse Event Reporting System database identified several cases of gastrointestinal perforation (life-threatening or with mortality) across the range of agents administered for the treatment of OIC or other constipation types. Methylnaltrexone in the subcutaneous form was the first PAMORA approved for OIC. Its real-world use in the ∼6 years before the availability of another OIC-indicated PAMORA helped establish the adverse-event profile of the class, and experience has been gained in identifying and treating appropriate patient populations. Class labeling of PAMORAs includes a contraindication in patients with known or suspected gastrointestinal obstruction or increased risk of recurrent obstruction. Appropriate patient selection during laxation therapy for OIC, regardless of treatment plan, involves consideration of the overall risk versus benefit in patients at increased risk of perforation due to comorbid medical conditions, concurrent medications, or recent gastrointestinal procedures. After initiating treatment for OIC, clinicians should assess the effectiveness of laxation therapy and carefully monitor for signs of gastrointestinal perforation.

TPS6111 Background: Human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) has surpassed cervical cancer as the most common HPV-related cancer in the US, with the majority being caused by HPV16. Persistent expression of HPV16 oncoproteins E6 and E7 by host genome may promote HNSCC. HPV16-positive HNSCC may be associated with poor clinical outcomes in the recurrent/metastatic (R/M) setting. PDS0101 (Versamune HPV) is an HPV16-immunotherapy that generates a potent, targeted T cell attack against HPV16 E6 & E7. In a Phase 2 study, PDS0101 plus pembrolizumab has shown encouraging safety and survival benefit in patients with HPV16-positive R/M HNSCC. (Weiss J et al. ESMO 2024. Poster 879P. NCT04260126). Methods: VERSATILE-003 is a global Phase 3, randomized, controlled, open-label study evaluating PDS0101 plus pembrolizumab vs. pembrolizumab in patients with HPV16-positive R/M HNSCC with PD-L1 positive disease (CPS ≥1). Key eligibility criteria include age ≥18-years-old, histologically- or cytologically-confirmed diagnosis of R/M HNSCC with primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx and no prior systemic anticancer treatment in the R/M setting, HPV16 tumor positivity (centrally tested), PD-L1 positivity defined as CPS ≥ 1 using FDA-approved PD-L1 IHC 22C3 pharmDx kit, and measurable disease based on RECIST 1.1 confirmed by blinded independent central review (BICR). Patients will be randomized 2:1 to receive pembrolizumab 200 mg IV Q3W with PDS0101 1 mL SC administered concurrently during Cycles 1, 2, 3, 4, and 12 (investigational arm), or pembrolizumab 200 mg IV Q3W alone (control arm). The primary objective is to compare overall survival (OS) between the investigational and control arms. Secondary objectives include objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and progression-free survival (PFS) using RECIST 1.1 and assessed by BICR. Exploratory objectives include tumor response assessed by investigator and by irRECIST, PFS2, quality of life as assessed by EQ-5D, QLQ-C30, and QLQ H&N35, and assessment of ctHPVDNA. Updated enrollment data will be provided. Clinical trial information: NCT06790966 .

e12502 Background: In March 2022, the United States Food and Drug Administration approved olaparib as adjuvant treatment (tx) for patients with germline BRCA1/2 pathogenic or likely pathogenic variants and HER2-negative eBC at high risk of recurrence who have been treated with neo-adjuvant or adjuvant chemotherapy. Approval was based on results from the OlympiA trial which demonstrated a significant increase in invasive-disease free survival [hazard ratio, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001] and overall survival [hazard ratio, 0.68; 99% CI, 0.47-0.97; P=0.009] with olaparib vs placebo. To date, there has been limited real-world data for eBC on olaparib utilization patterns and characteristics of olaparib users. Methods: This retrospective analysis using closed claims from KHM included adult pts with HER2-negative eBC receiving first olaparib prescription (index date) from March 11, 2022 to Nov 30, 2023. Continuous medical and pharmacy enrollment of ≥12 months pre-index and ≥30 days post-index was required. Pt characteristics were summarized descriptively, and Kaplan-Meier (KM) analysis was conducted for time-to-event utilization outcomes. Outcomes were evaluated for pts overall and stratified by hormone receptor (HR) status and race/ethnicity. Non-persistence was defined as minimum of 2 consecutive missed prescription fills. Medication possession ratio (MPR) was calculated as the sum of days of olaparib supply, divided by the total number of days from olaparib initiation to the last claim plus days of olaparib supply in the last claim. Results: We identified 176 pts with HER2-negative eBC who received olaparib. Median age was 44 years, and the majority (66.5%) had commercial insurance. KM-calculated median persistence on olaparib was 11 months (95% CI: 9.2-12.2); overall, adherence measured by MPR ≥80% was 74.2% by month 6 of olaparib use; adherence is higher among Caucasian than non-Caucasian pts (Table). While the majority of HR+/HER2- pts (77.9%, N=53/68) took olaparib concurrently with other (88.7% hormonal) adjuvant tx, most TNBC pts (70.4%, N=76/108) received olaparib alone. Among TNBC pts who took olaparib concurrently with other adjuvant tx (N=32/108), 81.3% received olaparib combined with immunotherapy. Conclusions: Our study provides evidence of favorable persistence and adherence to adjuvant olaparib in a real-world setting and data on utilization of olaparib concurrently with other tx. Recent approvals of other adjuvant tx for HER2- high-risk eBC warrants further research on the efficacy of olaparib used alone, versus olaparib combined or sequenced with other treatments. Olaparib MPR ≥80% by follow-up time points between Caucasians and non-Caucasians. Cohorts 30 days 60 days 180 days 365 days Caucasians (N=70) 92.5% 71.7% 80.6% 90.9% Non-Caucasians(N=55) 88.7% 66.7% 70.0% 50.0%

7507 Background: CARTITUDE-1 evaluated cilta-cel in pts with heavily pretreated RRMM who historically have an expected median progression-free survival (PFS) of <6 months (mo) and median overall survival (OS) of ~1 year (y). At 33.4 mo median follow-up, median PFS was 34.9 mo, and median OS was not reached (36-mo OS rate, 62.9%; Lin et al, ASCO 2023). We report OS, ≥5 y progression-free outcomes, and safety with a median study follow-up of 60.3 mo. Methods: Pts in CARTITUDE-1 received a single cilta-cel infusion. Correlative analyses were performed utilizing drug product, baseline, and postinfusion samples. Pts are followed for progression, survival, and safety in a 15-y follow-up study, CARTinue (NCT05201781), with pt evaluations per local standard of care (reported annually at a minimum). Results: Of 97 pts treated, 32 (33.0%) remain alive and progression free for ≥5 y after cilta-cel, without further MM treatment. For these 32 pts, prior to enrollment in CARTITUDE-1, median time from start of last line of therapy (LOT) to progression was 4.0 mo (range, 0.7–48.6). Among the 32, median age was 60 y (range, 43–78), median number of prior LOT was 6.5 (range, 3–14), 23.3% had high risk cytogenetics, 12.5% had extramedullary disease (EMD), 90.6% were triple-class refractory, and 46.9% were penta-drug refractory. Baseline characteristics of pts who were progression free for ≥5 y, including those with high-risk cytogenetics and EMD, were comparable to pts with progressive disease (PD) within 5 y. Compared with pts who had PD within 5 y, biomarkers significantly associated with ≥5 y progression free status included a higher fraction of naïve T cells in the drug product, lower neutrophil to T cell ratio, higher hemoglobin and platelets at baseline, and higher effector-to-target ratio (Cmax to sBCMA at baseline). At Cmax, these pts also had significantly higher CD4 central memory CAR+ T cell subsets and CAR+ T cells that were positive for the activation markers CD38, CD25, and PD-1. Data were collected on a subset of pts from a single center where local serial MRD assessments were performed. All 12 pts at this center who were progression free for ≥5 y were MRD negative at 10 –6 and imaging negative by PET/CT yearly for 5 y. Overall, at 60.3 mo median follow-up in CARTITUDE-1 (N=97), median OS was 60.6 mo (95% CI, 41.9–NE). With continued follow-up, 3 additional pts reported a second primary malignancy (1 of which was acute myeloid leukemia; onset, 2.8 y after infusion). No new cases of movement and neurocognitive disorders were reported. Conclusions: The median OS for pts enrolled in CARTITUDE-1 was 5 y, and 33% of pts remain progression free for ≥5 y following a single cilta-cel infusion. These data provide the first evidence that cilta-cel is potentially curative in pts with RRMM. Clinical trial information: NCT03548207 , NCT05201781 .

7506 Background: IV Isa-Pd is approved to treat RRMM patients (pts) based on the ICARIA-MM study. A Phase 1b study showed safety and efficacy of Isa SC via an OBDS, an investigational wearable bolus injector, plus Pd, in RRMM pts. Isa SC offers shorter duration, fixed dose and smaller administration volume. Here, we report results of the IRAKLIA trial (NCT05405166); Isa SC vs IV + Pd in RRMM pts, the first Phase 3 myeloma trial reporting the use of an OBDS. Methods: This multicenter, open-label study enrolled pts aged ≥18 years with ≥1 prior line of therapy (LOT). Pts were randomized 1:1 to Isa SC (1400 mg) or Isa IV (10 mg/kg) weekly in Cycle (C)1, then every 2 weeks + P (4 mg/day, Day [D]1–21) + d (40 mg [20 mg if age ≥75 years] weekly). Pts had 4-week cycles until progression, unacceptable toxicity or patient request. Co-primary endpoints were overall response rate (ORR; non-inferiority [NI] margin of 0.839) and Isa trough level (C trough ) at steady state (predose at C6D1; NI if lower limit of 90% CI of geometric mean ratio ≥0.8). Results: 531 pts (SC n=263; IV n=268 [4 not treated]) were randomized. Baseline characteristics were balanced (median age 66 years; median 2 prior LOT). After median 12 months follow-up, ORR was 71% (SC arm) and 71% (IV arm; relative risk [95% CI] = 1.008 [0.903–1.126]; lower CI > NI margin). Mean (SD) C trough at C6D1 was 499 (259) μg/mL for SC and 340 (169) μg/mL for IV. C trough geometric mean ratio (90% CI) was 1.532 (1.316–1.784); lower CI > NI margin. Co-primary and all 4 key secondary endpoints including pt experience are in the Table. Grade ≥3 treatment-emergent adverse events occurred in 82% (SC) and 76% (IV) of pts; with treatment discontinuation rates of 8% and 9%. Injection site reactions (ISRs) occurred in 4% (11/263) of the SC arm and in 19 (0.4%) of 5145 SC injections (all Grade 1–2). 99.9% of OBDS injections were completed without interruption. Conclusions: IRAKLIA met its co-primary endpoints, showing efficacy and pharmacokinetic NI between Isa SC vs IV + Pd. No new safety signal besides a low ISR incidence was observed, showing excellent Isa SC tolerability. Far fewer infusion reactions and higher pt satisfaction were also noted for SC vs IV. Efficacy and safety are comparable to Isa IV in ICARIA-MM. These results support potential use of Isa SC delivered via the OBDS, designed to improve pt experience and practice efficiency. Clinical trial information: NCT05405166 . Isa SC + Pd Isa IV + Pd Efficacy, % N=263 N=268 ORR 71 71 ≥VGPR 46 46 PK*, µg/mL N=131/121 N=126/121 Geometric mean Isa C trough at C2D1 / C6D1 360/426 277/278 Safety, % N=263 N=264 All grade IR 2 25 Pt satisfaction with injection method at C5D15, % 70 53 *PK was analyzed at C6D1 with PP PK population and at C2D1 with PP CT4W population. CT4W, C trough at 4 weeks; IR, infusion reaction; PK, pharmacokinetics; PP, per protocol; VGPR, very good partial response.

e13887 Background: Oncology and Hematology patients in rural areas lack access to specialty care. We report a successful implementation of a virtual care model in this specialty. The initial pilot was conducted in Tomah Wisconsin, a Mayo Clinic Health System site. The clinic was scheduled for two afternoons per month. We report the data on the practice during the first quarter of 2023 where these patients were seen using a Teladoc Mini device and virtual care platform. A total of 18 Teladoc physician visits were completed with 14 unique patients seen using this technology. During that period, six patients received intravenous or injectable treatments for cancer with a total of 21 treatments given. The patient time saved was 90 mins per encounter for travel. Most of the patients were older, with half the patients aged 75 or older and one third of the patients 80 years or older. Based on the suceessful inital implementation, the platform was expanded to 3 additional rural Wisconsin Sites: Arcadia WI, Sparta WI, and Prarie du Chein WI. The system then expanded to other sites within the Mayo Clinic Health System in Wisconsin. Methods: A retrospective, 3-month longitudinal analysis of the patients seen via Teladoc for Oncology and Hematology from January 2023 through March 2023 in Tomah Wisconsin. Results: Over the period of analysis, 14 unique patients were seen for a total of 18 physician Teladoc visits. Of those 14 patients, six were on treatment for their cancer (either intravenous or injection). A total of 21 treatments were completed. The patients ranged in age from 52 to 89 with an average age of 72. Eight patients were male and six were female. Conclusions: With the looming oncology workforce shortage, access to specialty care for rural populations will be even more difficult in the coming years. In the current marketplace, virtual care in oncology and hematology is limited to expert opinion rather than implementation of Teladoc technology. Creative ideas are needed to improve the efficiency of the workforce and the access for patients in rural populations. Using the Teladoc technology allows for improved access to the oncology and hematology service line in the Tomah Wisconsin area of the Mayo Clinic Health System. Most of the patients that were seen in this analysis were 75 years or older. This technology not only saves time for patients, but also their caregivers that often must accompany the patients for treatment. Nearly half the patients seen with Teladoc technology were given some form of IV or injectable therapy. This technology decreases the burden on patients and family members, particularly the accompanying family members that are non-salary (e.g., hourly) employees. The patients that favored the Teladoc technology were those who had limited access to technology and high-speed internet access. Based on the successful implementation, the Teladoc technology was expanded to other sites for the oncology and hematology service line.

e12568 Background: Modern preventive screening have made it possible to identify ductal carcinoma in situ (DCIS). Progression of DCIS to invasive disease is known to be driven by somatic evolution and affected by clinical interventions. Yet studies indicate that only 20–30% of the cases of DCIS will progress further if not treated, implying that a large portion of patients are over treated. Recognizing which pre-cancerous tumors are likely to progress to cancer or recur as DCIS after initial treatment is of great importance to optimize treatment options, lower associated risks and allocate healthcare efforts to patients that most benefit from early treatment. Methods: This study consists of a retrospective cohort of 158 patients, 57 of which had a DCIS recurrence over 2 to 228 months after treatment, and 45 progressed to invasive disease over 12 to 180 months. We generated a digital pathology library consisting of hematoxylin and eosin (H&E) stained whole slide images (WSI), and applied machine learning methods to perform duct and nuclear segmentation followed by cell classification. We then computed a set of spatial statistics from landscape ecology to characterize each sample. We used LASSO on half of the data (the training set) to select a Cox proportional hazards model that predicted recurrence of DCIS or cancer and used the other half of the data (the test set) to validate the predictors in the Cox model. Results: When considering the time to recurrence as disease-free survival (DFS), the type of DCIS treatment stratifies patients between Lumpectomy Only and More than Lumpectomy groups (log-rank test p-value < 0.0001), recapitulating previous results. When the subset of patients that had more than a lumpectomy was analyzed using spatial landscape ecology metrics, a decrease in the interaction between tumor cells and fibroblasts and between tumor cells and lymphocytes, measured by the mean nearest neighbor distance, were associated with improved DFS (concordance = 0.717) in the model validation set. Stratification of samples by the median risk is discriminatory with a p-value < 0.001. Alternatively, decreased nearest neighbor distance between lymphocytes and fibroblasts was associated with the time to invasive disease (p-value < 0.05). Conclusions: Integrating spatial ecological statistics of cell distributions enhances risk stratification of DCIS samples beyond the known effects of early treatment. Our results highlight the importance of ecological mechanisms in recurrence, progression and treatment resistance. The risk associated with spatial interactions of lymphocytes and fibroblasts suggests previously unknown ecological interactions may be associated with early micro-metastases that result in breast cancer even after mastectomy or lumpectomy with radiation in patients with DCIS.