Citations

6557 Background: Trials that inadequately include underrepresented minority (URM) populations widen inequities in cancer care. We assessed reporting patterns, representation, and trends of URM representation in breast cancer (BC) trials. Methods: We analyzed all phase 2/3 trials for age disparity and trials recruiting from the US for racial/ethnic disparity amongst BC RCTs (1990-2021). Enrollment-incidence ratios (EIR), which compare trial proportions (TP) from age subgroups against global estimates of incidence in the corresponding age group (from Global Burden of Disease) and racial/ethnic subgroups against US-population-based incidence in the corresponding racial/ethnic group (from SEER 22), were calculated. Individual-trial EIRs were pooled using random-effects meta-analyses. EIRs of <0.80 indicated meaningful underrepresentation, while EIRs >1.20 indicated meaningful overrepresentation. Meta-regression was used to explore associations between key trial characteristics and EIR, and trends in EIR over the last three decades. Results: Of 842 global trials with 490,657 participants, 232 (27.6%) reported the number of participants in specific age strata and 144 (17.1%) reported outcomes by age. Only 60 trials recruited exclusively from the US. Of these, 41 (68.3%) reported race and 24 (40.0%) reported ethnicity, and 2 (3.3%) analyzed outcomes by race. Older adults aged ≥65 years (TP: 24.3%; EIR: 0.53 [95% CI: 0.47-0.60]) and Hispanic women (TP: 5.3%; 0.54; 0.40-0.75) were underrepresented across global trials and US-only trials respectively. Black women were significantly underrepresented in trials that led to FDA approval (0.38; 0.25-0.58) but not in US-only trials. Stratified analysis by BC subtype (with subtype-specific population incidence) showed underrepresentation of Black women in US-only trials for HER2+ BC (0.66; 0.47-0.93), Hispanic women in ER+ BC (0.42; 0.20-0.90), Asians in triple-negative BC (0.24; 0.11-0.53), and older women in HER2+ BC (0.35; 0.31-0.40) and triple-negative BC (0.36; 0.29-0.45). From 1990-2021, the representation of older women declined significantly (meta-regression coefficient for EIR: -0.4 per 10 years), while Black and Hispanic representation showed no significant change. Black (p = 0.02) and Hispanic representation (p = 0.05) worsened significantly in larger trials. Conclusions: Published reports of BC trials do not consistently report the inclusion of URM. Older and Hispanic women were consistently underrepresented, whereas Black women were underrepresented in large, practice-changing trials. [Table: see text]

6551 Background: Despite recent advances in lung cancer therapeutics leading to considerable improvement in survival, disparities continue to persist among socially disadvantaged populations. Although the reasons underlying this phenomenon are uncertain, we posit that neighborhood-level factors could play a role. Furthermore, neighborhood disadvantage may lead to epigenetic changes which promote malignant progression. This study aimed to determine the effects of neighborhood-deprivation index (NDI), a validated 13-factor-based measure, that combines income, education, employment, and housing in a neighborhood, on lung cancer mortality. Methods: A retrospective cohort study assessed the relationship of NDI with survival weighted by age, stage, and DNA methylation among biopsy-proven lung cancer from two U.S. medical centers, Johns Hopkins University and the University of Illinois Chicago, between 2008-2020. In our analysis, U.S.-standardized NDI values for each year of sample collection were computed at the U.S. census tract level and categorized into quartiles. Participants’ residential addresses were geocoded to U.S. census tracts and linked to NDI quartiles. DNA extraction from liquid biopsy samples was performed for quantification of DNA methylation. Results: The study included 184 lung cancer patients, with 89 in the low-deprivation group and 95 in the high-deprivation group. The high-deprivation group had a higher percentage of females (57% vs. 48%), a higher percentage of African Americans (AA) (50% vs. 36%), a lower pack-year smoking history (30 vs. 39 median pack-years), and a higher percentage with stage IV disease (28% vs. 20%) than the low-deprivation group. Overall, NDI was significantly higher among AA when compared with Whites (p=0.003) and associated with lung cancer stage at diagnosis with an odds ratio of 1.17 (p=0.02). There was a significant correlation between DNA methylation and stage for HOXA7, SOX17, ZPF42, TAC1 and HOXA9. Only HOXA7 DNA methylation correlated with NDI (p=0.003).The high-deprivation group had a significantly shorter survival duration compared to the low-deprivation group, with a 1-year survival rate of 79% vs. 90%, a 2-year survival rate of 70% vs. 84%, and a 5-year-survival rate of 51% vs. 73% (p=0.02). After adjusting for age at diagnosis, stage, and DNA methylation status, belonging to the high-deprivation group was associated with a higher mortality risk with a hazard ratio of 2.02 (p=0.04). Conclusions: Neighborhood-level socioeconomic status and DNA methylation may be associated with late stage lung cancer at diagnosis; whereas NDI shows a potential association with shorter survival and increased mortality risk. Higher neighborhood deprivation among AA suggests that changes in health care policy that account for neighborhood-level indices of socioeconomic deprivation may enable more equitable improvement of lung cancer mortality.

6548 Background: National organizations (ASCO, ACS, ACCR) have advocated for routine collection of sexual orientation and gender identity (SOGI) in cancer clinics to advance cancer health equity. In 2017, only 24% of NCI Community Oncology Research Program (NCORP) practices collected sexual orientation (SO) data, while 10% collected gender identity (GI) data; recent progress in collection is unknown. Methods: In 2022, NCORP practices again completed a Landscape Assessment to assess research capacity (funding support from 2UG1CA189824) and were asked whether they routinely collect SOGI data in the electronic health record (EHR). The proportions of practices reporting collection of SO and/or GI data and population level differences over time were calculated using Fisher’s exact tests. Univariate associations between SOGI data collection and site-related variables were evaluated using logistic regression; significant associations were then tested in separate multivariate logistic regression models. Results: 271 practices responded to the Landscape Assessment; 42% (114) reported that they routinely collect SO data, 58% (157) reported that they collect GI data; both were significantly higher than 2017 (p<0.001). Compared to other regions, practices in Northeastern states were significantly more likely to report collecting GI, but not SO. Practices with higher proportions of White patients were also more likely to collect GI (p < 0.001). Practices with community outreach staff were more likely to collect SO (Table 1). There were no significant differences in SOGI collection by Medicaid/Medicare patients, new cancer cases per year, or practice ownership. In both 2017 and 2022, sites in Southern states were less likely to collect GI than sites in other regions. Conclusions: Progress was made in SOGI collection between 2017 and 2022, but fewer than half of NCORP sites routinely collect SOGI data, in spite of national guidelines. Further examination of the cultural context of SOGI collection could inform efforts to improve data collection in the South and other regions. The lack of data on sexual and gender minority patients in the EHR contributes to health inequity and deficiencies in patient-centric care. [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.

6526 Background: In the current literature, the association between social determinants of health (SDH) and head & neck-nervous system cancer (HNNsC) is limited by the narrow scope of SDH assessed and the broad classifications of HNNsC. Our study utilizes the CDC-Social Vulnerability Index (SVI) to assess both the individual and collective impact of four social determinant themes on various HNNsC in US adults. Methods: This study utilized the SEER database to evaluate 116,373 adult patients from 1975-2017 who presented with HNNsC. Patients were assigned SVI scores based on county-of-residence at the time of diagnosis, encompassing total-SVI score and 4 sub-scores of socioeconomic status, minority-language status, household composition, and housing-transportation. Using these scores, univariate linear regressions were used to assess patient care (months of follow-up) and prognosis (months of survival). Results: As total-SVI score increased, decreases in months of follow-up (MOF) and months of survival (MOS) were observed for many HNNsC tumors (p less than 0.001) when comparing the lowest to highest vulnerability cohorts. There was a decrease ranging from 3.55-36.6% in the MOF, with the largest decreases occurring in embryonal, anaplastic oligodendroglioma, and anaplastic ependymoma tumor types, with the largest sub-score contribution coming from socioeconomic status for these three disease classes. Similarly, there was a decrease ranging from 6.90-45.81% in the MOS, with the largest decreases occurring in anaplastic ependymoma, anaplastic astrocytoma, and pilocytic astrocytoma tumor types with the largest sub-score contribution coming from socioeconomic status for these three disease classes. Increases in vulnerability within SDH themes contributed significantly to these total-SVI trends in MOF and MOS, with each social determinant impacting different disease classes to varying extents. Socioeconomic status was the most impactful sub-score for MOF in nine of fourteen disease classes, followed by housing-transportation and household composition, each leading the impact of two of fourteen disease classes, and minority-language status leading the impact of one of fourteen disease classes. Similarly, socioeconomic status was the most impactful sub-score for MOS in eight of fourteen disease classes, followed by housing-transportation leading the impact of three of fourteen disease classes, household composition leading the impact of two of fourteen disease classes, and minority-language status leading the impact of one of fourteen disease classes. Conclusions: The results of this study show that with increasing social vulnerability, there is a significant decrease in both the care (follow-up) and the prognosis (survival) of US adults with HNNsC and highlight which SDH contributes more to disparities.

6520 Background: Increased patient engagement in decision making may mitigate disparities in breast cancer surgical care. Socioeconomically disadvantaged patients disproportionately experience barriers to engagement. Decision aids (DA) increase engagement by providing information, establishing role expectations during the consult, and increasing confidence in surgeon interactions. The objective was to test the effectiveness of a surgical web-based DA in increasing engagement among breast cancer patients in clinics that care for a high proportion of socioeconomically disadvantaged patients. Methods: A stepped wedge trial was conducted with 10 NCI Community Oncology Research Program clinics (Alliance for Clinical Trials in Oncology Research Base, 6/19-12/21). Clinics were randomized to time of transition from usual care (UC) to delivery of a web-based DA. Patients with stage 0-3 breast cancer eligible for surgery provided consent prior to a surgical consult. Socioeconomic disadvantage was assessed with the Area Deprivation Index measured at the zip+4 level and dichotomized. Patient engagement was measured by Patient’s Self-Efficacy in Patient-Physician Interactions (PEPPI-5, follow-up survey) and count of Active Patient Behaviors (Street protocol, audio recorded consult). Intervention effects were tested with linear mixed-effects models, accounting for surgeon and clinic-level clustering, time, and enrollment post-COVID. Heterogeneity of treatment effect by socioeconomic disadvantage was assessed with an interaction term. Results: 573 patients enrolled. 44% (136/309) reviewed the DA. No significant difference in engagement was observed comparing DA and UC for PEPPI-5 (-0.80 [95% CI -2.13, 0.54], p = 0.24) or Active Patient Behaviors (2.52 [CI -4.11, 9.15], p = 0.46). Enrollment post-COVID was associated with increased Active Patient Behaviors (9.59 [CI 1.76, 17.43], p = 0.02) but no change in PEPPI-5 (-1.31 [CI -2.88, 0.26], p = 0.10). No heterogeneity of treatment effect was observed. Conclusions: In this trial conducted in clinics that serve diverse populations, no significant relationship was observed between a web-based DA and patient engagement. Conducting this stepped wedge trial during the pandemic was challenging. Future analyses will explore the impact of COVID on outcomes and effect of the decision aid for patients who reviewed it. UG1 CA189823; AHRQ R01HS025194; https://acknowledgments.alliancefound.org . Clinical trial information: NCT03766009 . [Table: see text]

6509 Background: Accrual of underrepresented populations (URPs-racial and ethnic minorities, women, rural populations, and younger and older populations) to clinical trials has been historically low, hampering progress in cancer treatment, symptom intervention and prevention for all. In 2018, the Alliance for Clinical Trials in Oncology (Alliance), as a part of the NCI's National Clinical Trials Network (NCTN) and a Research Base for the NCI Community Oncology Research Program (NCORP) began a multi-pronged strategy to increase accrual of underrepresented minorities by race and ethnicity (URMs) to both treatment and cancer control trials conducted by the Alliance. Methods: Alliance leadership set a goal of 20% accrual for racial and ethnic minorities to all trials in 2018. The Health Disparities Committee (HDC) implemented several strategies over time including leadership promotion/expectation of goals; funding junior investigators and special projects focusing on URPs; working groups for specific populations in HDC; HDC co-chairs to selected protocols; translation services of patient facing materials; opening studies at NCORP Minority Underserved Sites; real time monitoring of accrual demographics, by Alliance and by site; protocols addressing aims for specific populations; closing protocol enrollment to majority populations; and increasing the study sample size to enroll additional minority participants to allow for analyzing intervention effects by subgroups. Results: Accrual data from 117 NCTN and NCORP trials led by Alliance was included from 2014-2022. Over time, accrual of racial and ethnic minorities increased from 13.6% to 25.3% for treatment and 13% to 21.5% for cancer control trials. This results in overall increase from 13.5 % to 23.6% of URMs for all trials, a 74.8% improvement. Conclusions: Intentional approaches to increase URMs has led to an increase in URM accruals to Alliance trials. Future strategies include implementation of the Alliance Patient Questionnaire to prospectively measure the prevalence of specific social determinants of health among patients enrolled to further expand the understanding and address the needs of unique population accrued to Alliance trials. In addition, accrual of women, rural populations, and younger and older adults (65+ years) are now being monitored over time to increase all URP accruals.

e18097 Background: Sorafenib and lenvatinib are FDA-approved MKIs for locally recurrent or metastatic, progressive, DTC refractory to radioactive iodine treatment. Cabozantinib showed a survival benefit in radioiodine-refractory DTC previously treated with sorafenib and/or lenvatinib and was granted FDA approval. Our study aims to investigate the benefit of other MKIs in DTC beyond the first-line setting. Methods: DTC patients (pts) treated with multiple lines of MKIs from August 2018 to July 2022 at Mayo Clinic across all sites were identified. Electronic medical records were reviewed. 6-month, 12-month, and 18-month progression-free survival (PFS) were calculated for all lines of therapy using RECIST 1.1 criteria. Results: Among the 9 pts identified, 4 were male. The median age was 65 years (43-75). Most pts (60%) had papillary thyroid cancer. All pts received lenvatinib as first line treatment. The 6, 12 and 18-month PFS were 89%, 89%, and 55% respectively. 6 pts discontinued lenvatinib due to progression of disease (PD). 3 pts discontinued it due to adverse effects (AEs), which included hemoptysis (1 pt), severe rash (1 pt) and multiple psychiatric manifestations (1 pt). 8 pts received pazopanib, and 1 patient received cabozantinib with ipilimumab (1 dose) and nivolumab (6 months - discontinued due to myocarditis) as second-line therapy. Among them, 1 patient received pembrolizumab plus everolimus for 2 months before receiving pazopanib. The 6, 12 and 18-month PFS were 55%, 22%, and 11% respectively. All pts ceased treatment due to eventual PD, and there were no toxicity-related discontinuations. 5 pts subsequently received third-line MKIs, including cabozantinib (3 pts), pazopanib (1 pt), and lenvatinib (1 pt). The pt who received lenvatinib had discontinued it as first line therapy due to toxicity. The 2 pts treated with third-line cabozantinib and the pt rechallenged with lenvatinib showed no PD at 12-months and no toxicity related discontinuation. Conclusions: Pazopanib was associated with durable PFS and good tolerability when offered after PD or intolerance on lenvatinib in this retrospective analysis, warranting a randomized prospective study. [Table: see text]

6036 Background: E3311 is a phase II randomized study of intermediate risk HPV+ OPC patients who underwent TOS by credentialed surgeons and were then treated by pathology-guided, deintensified post-operative treatment. Recent retrospective population data suggest that time to post-operative radiotherapy (PORT) > 6 weeks is associated with worse progression-free survival (PFS). Methods: We retrospectively analyzed demographics, pathologic characteristics, and oncologic outcomes in E3311 by time to initiation of PORT (short vs long, exploring both 6 and 7 weeks postop as the cutpoint). Binary and categorical variables were compared using a chi-square test (or a Fisher’s exact test for small sample sizes). Ordinal variables were compared using a Wilcoxon rank sum test. PFS and overall survival (OS) were estimated using the Kaplan-Meier method and compared using a log-rank test, which was stratified by intermediate- (Arms B/C) vs high-risk (Arm D). Results: Among 321 evaluable patients, the median time to initiation of PORT was 5.1 weeks (range 0.7-15.7); 5.0 (0.7-15.7) for Arm B, 5.1 (2.4-7.0) for Arm C, 5.6 (3.6-7.9) for Arm D. No significant difference in PFS or OS was observed whether PORT commenced by 6 or 7 weeks postoperatively, compared with longer time to initiation of PORT (p = 0.62 and 0.65, p = 0.30 and p = 0.41, respectively). 3-yr PFS rates were 93.5% (95% CI: 89.4%, 96.0%) among those treated ≤6 weeks, and 91.2% (95% CI: 81.4%, 95.9%) among those treated > 6 weeks; 3-yr OS rates were 96.1% (95% CI: 92.7%, 98.0%) among those treated ≤6 weeks, and 94.1% (95% CI: 84.9%, 97.8%) among those treated > 6 weeks. No significant differences in outcomes were observed between intermediate risk treatment arms (deintensified (50Gy) or standard dose (60Gy) RT). Additional demographic and pathologic characteristics, including primary site, margin status, histologic grade, stage, and extranodal extension were not significantly different between those with short vs long time to PORT, whether 6 or 7 weeks was used as the cutpoint. There were more T2 tumors in those treated > 7 weeks postop (84% vs. 49%, p = 0.007). PS = 1 patients were more numerous among those with shorter time to PORT (10% vs 0%, with the 7 week cutpoint). Conclusions: In contrast to retrospective NCDB data, intermediate- and high-risk HPV+ OPC patients enrolled on E3311 had favorable 3-yr PFS and OS rates that were not significantly worse when adjuvant therapy was started > 6 wks or > 7wks. These results argue against a survival advantage for initiation of PORT within 6 or 7 weeks for early-stage HPV+ OPC managed with high-quality transoral resection. The optimal time window to initiate PORT in HPV+ OPC patients remains to be determined. Clinical trial information: NCT01898494 .

6012 Background: Up to 70% of oropharyngeal cancers in the US are reported to be HPV-mediated with most caused by HPV16 infection. First line treatment for patients with unresectable, recurrent or metastatic (R/M) disease is pembrolizumab with or without chemotherapy, but most patients eventually experience disease progression. PDS0101 is a novel, investigational HPV16-targeted immunotherapy that stimulates a potent, targeted T cell attack against HPV16-positive cancers. Methods: VERSATILE-002 (NCT04260126) is an open-label, non-randomized, Simon 2-stage study evaluating the combination of PDS0101 and pembrolizumab in subjects with HPV16-positive R/M HNSCC in 2 cohorts: ICI-naïve and ICI-refractory. All subjects receive pembrolizumab IV Q3W with PDS0101 SC administered concurrently during Cycles 1, 2, 3, 4, and 12 (max 5 doses). The primary endpoint of the study is confirmed Best Overall Response per RECIST 1.1. Herein we update the safety, PFS, and OS data for the ICI-naïve subjects. Results: Forty-eight subjects who received at least one cycle of combination therapy (safety population) had a median age of 62.5 (range 45 – 83), were 93.8% male, 93.8% White, and 62.5% ECOG 0. Among this population, the median overall treatment duration in months was 3.5 (range 0.0 – 19.5). The median number of PDS0101 doses was 4 (range 1 – 5); 56.3% received 4 doses and 22.9% received 5 doses. The median number of pembrolizumab doses was 5 (range 1 – 29); 27.1% received ≥10 doses. Efficacy was evaluated in 34 subjects (47.1% with CPS ≥20) who had assessment of tumor response following treatment (efficacy population). Tumor reduction (maximum percent change from baseline) was seen in 23 (67.6%) subjects. Nine subjects (26.5%) had confirmed response including 1 CR and 8 PR, 15 subjects had SD (44.1%), and 9 subjects had PD (26.5%). One subject was not evaluable (2.9%). The median PFS was 10.4 months (95% CI 4.2, 15.3). Among the safety population, median overall survival was non-estimable due to the ongoing survival status of study subjects. The estimated 12-month OS rate was 87.1%. Thirty-three (68.5%) subjects had mild or moderate (Grade 1 or 2) PDS0101-related TEAE (TRAE); the most common were fatigue and injection site reactions (ISRs). Only 3 subjects (6.3%) had Grade 3 TRAEs: fatigue, ISR, blood alkaline phosphatase increased, and hyperglycemia. No subjects had Grade 4 or 5 TRAE. No subject came off study due to toxicity. Conclusions: PDS0101 with pembrolizumab is well tolerated in this ICI naïve R/M HPV-associated HNSCC population. Median PFS was 10.4 months which compares favorably to published median PFS of 2-3 months for approved ICIs when used as monotherapy in patients with similar PD-L1 levels. The estimated 12-month OS of 87.1% is promising compared to published results of about 36-50%. These results justify a confirmatory randomized, controlled study. Clinical trial information: NCT04260126 .