Representativeness of Study Participants

PURPOSE:Subprotocol K2 (EAY131-K2) of the NCI-MATCH platform trial was an open-label, single-arm, phase II study designed to evaluate the antitumor efficacy of the oral FGFR1-4 inhibitor, erdafitinib, in patients with tumors harboring FGFR1-4 mutations or fusions. METHODS:Central confirmation of tumor FGFR1-4 mutations or fusions was required for outcome analysis. Patients with urothelial carcinoma were excluded. Enrolled subjects received oral erdafitinib at a starting dose of 8 mg daily continuously until intolerable toxicity or disease progression. The primary end point was objective response rate (ORR) with key secondary end points of safety, progression-free survival (PFS), and overall survival (OS). RESULTS:Thirty-five patients were enrolled, and 25 patients were included in the primary efficacy analysis as prespecified in the protocol. The median age was 61 years, and 52% of subjects had received ≥3 previous lines of therapy. The confirmed ORR was 16% (4 of 25 [90% CI, 5.7 to 33.0], P = .034 against the null rate of 5%). An additional seven patients experienced stable disease as best-confirmed response. Four patients had a prolonged PFS including two with recurrent WHO grade IV, IDH1-/2-wildtype glioblastoma. The median PFS and OS were 3.6 months and 11.0 months, respectively. Erdafitinib was manageable with no new safety signals. CONCLUSION:This study met its primary end point in patients with several pretreated solid tumor types harboring FGFR1-3 mutations or fusions. These findings support advancement of erdafitinib for patients with fibroblast growth factor receptor-altered tumors outside of currently approved indications in a potentially tumor-agnostic manner.

Adequate nutrition is paramount for proper growth and musculoskeletal, neurocognitive, and immunological development in infants, toddlers, and young children. Among breastfeeding mother-child dyads, this critical window of development, is impacted by both maternal and offspring dietary patterns. For mothers, their dietary patterns impact not only their own health and well-being, but also the nutrition of their breast milk - which is recommended as the sole source of food for the first 6 months of their infant's life, and as a complementary source of nutrition until at least 2 years of age. For infants and toddlers, the breast milk, formulas, and first foods they consume can have both short-term and long-term effects on their health and well-being - with important impacts on their taste perception, microbiome composition, and immune function. According to dietary intake data in the US, infants and young children meet a greater number of nutrient requirements than older children and adults, yet numerous disparities among socially disadvantaged racial/ethnic groups still provide significant challenges to achieving adequate nutrition during these early life stages. For example, Black children are at greater risk for disparities in breastfeeding, age-inappropriate complementary feeding patterns, nutrient inadequacies, food insecurity, and obesity relative to most other racial/ethnic groups in the US. For infants who do not receive adequate breast milk, which includes a disproportionate number of Black infants, dairy-based infant formulas are considered the next best option for meeting nutritional needs. Fermented dairy foods (e.g., yogurt, cheese) can serve as ideal first foods for complementary feeding, and cow's milk is recommended for introduction during the transitional feeding period to help meet the nutrient demands during this phase of rapid growth and development. Low dairy intake may put children at risk for multiple nutrient inadequacies and health disparities - some of which may have lifelong consequences on physical and mental health. A burgeoning body of research shows that in addition to breast milk, cow's milk and other dairy foods may play critical roles in supporting physical growth, neurodevelopment, immune function, and a healthy gut microbiome in early life. However, most of this research so far has been conducted in White populations and can only be extrapolated to Black infants, toddlers, and young children. Therefore, to better understand and support the health and development of this population, greater research and education efforts on the role of milk and dairy products are urgently needed. This review presents the current evidence on health disparities faced by Black children in the US from birth to four years of age, and the role that dairy foods can play in supporting the normal growth and development of this vulnerable population.

PURPOSE The National Cancer Institute Molecular Analysis for Therapy Choice trial is a signal-finding genomically driven platform trial that assigns patients with any advanced refractory solid tumor, lymphoma, or myeloma to targeted therapies on the basis of next-generation sequencing results. Subprotocol E evaluated osimertinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in patients with EGFR mutations. METHODS Eligible patients had EGFR mutations (T790M or rare activating) and received osimertinib 80 mg once daily. Patients with lung cancer with EGFR T790M were excluded. The primary end point was objective response rate (ORR), and the secondary end points were 6-month progression-free survival (PFS), overall survival, and toxicity. RESULTS A total of 19 patients were enrolled: 17 were evaluable for toxicity and 13 for efficacy. The median age of the 13 included in the efficacy analysis was 63 years, 62% had Eastern Cooperative Oncology Group performance status 1, and 31% received >three previous systemic therapies. The most common tumor type was brain cancers (54%). The ORR was 15.4% (n = 2 of 13; 90% CI, 2.8 to 41.0) and 6-month PFS was 16.7% (90% CI, 0 to 34.4). The two confirmed RECIST responses were observed in a patient with neuroendocrine carcinoma not otherwise specified ( EGFR exon 20 S768T and exon 18 G719C mutation) and a patient with low-grade epithelial carcinoma of the paranasal sinus ( EGFR D770_N771insSVD). The most common (>20%) treatment-related adverse events were diarrhea, thrombocytopenia, and maculopapular rash. CONCLUSION In this pretreated cohort, osimertinib did not meet the prespecified end point threshold for efficacy, but responses were seen in a neuroendocrine carcinoma with an EGFR exon 20 S768T and exon 18 G719C mutation and an epithelial carcinoma with an EGFR D770_N771insSVD mutation. Osimertinib was well tolerated and had a safety profile consistent with previous studies.

Abstract The Promise Fund is creating a systemic change in healthcare service delivery through its Continuum of Care model in which patients are provided health education, navigation for breast and cervical health, affordable early detection screenings, diagnostics, treatment, and/or support services through an established network of providers, reducing healthcare costs, alleviating the burden of our complex healthcare system, and improving patient outcomes. This model, established in Palm Beach County, has potential to be scaled across Florida and beyond. The Promise Fund's primary focus is to eliminate preventable deaths and stop the progression of breast and cervical cancer among women in South Florida. The region faces significant healthcare disparities, with over 80,000 uninsured women in Palm Beach County alone. Disproportionately affecting minority groups, these women often experience delayed diagnoses and higher mortality rates compared to White women. Barriers such as transportation, translation, education, and childcare further contribute to suboptimal survival rates, despite high cure rates exceeding 95% for breast and cervical cancer. Through public and private partnerships, the Promise Fund established a Women's Health Center co-located at a Palm Beach County Federally Qualified Health Center (FQHC). FHQCs are community-based facilities that provide comprehensive primary care services to uninsured or low-income individuals in areas of high need. At this strategically selected FQHC, the Promise Fund supplies state-of-the-art equipment for breast and cervical cancer screenings, such as a 3D Genius Mammography Machine, donated by Hologic, Inc., ultrasounds, LEEP, and colposcopy. To facilitate access, the Promise Fund employs over 20 patient navigators positioned in FQHCs, free clinics, and community-based organizations across South Florida. These navigators connect women to resources, engage in outreach, and enroll at-risk individuals into the program. The impact of the navigators is significant, with over 20,000 women engaged, over 80 cancers treated, more than 5,000 women finding medical homes, and over 19,000 women receiving education and outreach. Additionally, the program has facilitated over 4,000 mammograms and 2,000 pap tests, all provided at little to no cost to the patients. Promise Fund Patient Navigators are well-trained, culturally competent, and bilingual. They help patients overcome barriers to care, arranging transportation, childcare, and translation services. Our navigators are carefully selected from the community and undergo rigorous training in breast and cervical health, navigation, and reporting. Moreover, the Promise Fund supports patients throughout their cancer journey by brokering low-cost or free treatment from private hospitals. Despite the prevailing healthcare disparities, the Promise Fund's patient-centered approach has yielded positive outcomes. Over 98% of women navigated by the organization comply with receiving their screening mammogram, drastically surpassing the national average. Research has consistently demonstrated that patient navigators significantly improve patient outcomes by facilitating early screening and timely access to treatment, thus reducing disease progression and healthcare costs. Additionally, the Promise Fund’s expansive Continuum of Care model effectively decreases the time patients have to wait between diagnosis and starting treatment, as well as decreases the overall treatment time for patients. The success of the Promise Fund's inaugural Women's Health Center has led to the replication of this model in three additional FQHCs in Palm Beach and Broward County, ensuring that no woman in these areas should go without essential breast and cervical cancer resources. Citation Format: Nancy Brinker, Donna Shalala, Edith Mitchell, Haywood Brown, Wayne Frederick, Jane Mendez, Deeptee Jain, David Dodson, David Brodsky, Lillie Shockney. Developing a Continuum of Care Model to Address Healthcare Disparities in Breast and Cervical Cancer: The Promise Fund's Approach [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-10-10.

Supplementary Table S2: All Grades Treatment Related Toxicities (CTCAE v4).

Supplementary Table S4: HAQ Scores at different time points (n=970).

LBA503 Background: Black women experience higher rates of TIPN compared to White women when receiving weekly paclitaxel (WP) for early-stage breast cancer. This disparity impacts health equity, as TIPN leads to more frequent dose reductions and higher recurrence rates in Black women. Conversely, disparities in TIPN by race are not seen in women receiving every three-week docetaxel (3D). Further, retrospective analyses have identified specific genotypes associated with differential risk of grade 2-4 TIPN in women of African ancestry receiving WP . The primary aim of EAZ171 was to prospectively validate germline predictors of TIPN in Black women receiving WP. Secondary objectives included comparing rates of TIPN and dose reductions in Black women receiving WP compared to 3D. Methods: Women with early-stage breast cancer who self-identified as Black and were planned by physician choice to receive (neo)adjuvant WP (80mg/m2 x 12 doses) or 3D (75 mg/m2 x 4-6 doses) were eligible. Genotyping determined germline neuropathy risk, defined as high ( FCAMR homozygous wt or SBF2 mutated) or low (variant allele in FCAMR and SBF2 wt). Grade 2-4 TIPN by physician-reported CTCAE v.5 was compared between high vs. low risk genotypes, and between the WP vs. 3D arms at one year using Fisher exact tests with two-sided alpha of 0.1. Patient-rated TIPN was captured using PRO-CTCAE items, and patient-reported outcomes (PROs) assessed TIPN symptoms and functional interference (FACT/GOG-NTx, EORTC CIPN20). Results: 249 patients were enrolled between 6/27/19-3/31/22, including 121 receiving at least one dose of WP and 118 receiving a dose of 3D. Of those with genotype data, 91/117 (77.8%) in the WP arm and 87/118 (73.7%) in the 3D arm were classified as high risk. Physician-reported grade 2-4 TIPN was not significantly different in the high vs. low risk genotype groups with WP (47% vs. 35% p=0.27) nor with 3D (28% vs. 19% p=0.47). Grade 2-4 TIPN was significantly higher in the WP vs. 3D arm by physician-rated CTCAE (45% vs. 29% p=0.02) and PRO-CTCAE (40% vs. 24% p=0.03). Trends in worsening neuropathy scores were similar over time using the FACT/GOG-NTx and EORTC CIPN20 questionnaires, but were not significantly different between the two arms at 1 year. Patients receiving WP required more dose reductions due to TIPN (28% vs. 9% p<0.001) or due to any cause (39% vs. 25% p=0.02) than patients receiving 3D. Conclusions: In this prospective trial enrolling only Black women with breast cancer, germline variation did not significantly impact risk of TIPN with WP or 3D. However, 3D was more tolerable evidenced by less grade 2-4 TIPN and fewer dose reductions compared to WP. Given the disparate burden of TIPN and its potential impact on cure rates, this trial suggests docetaxel should be considered the preferred taxane for Black women with early-stage breast cancer. Clinical trial information: NCT04001829 .

Decades of health data show major health disparities occurring at every life stage between Black and White Americans. These disparities include greater mortality rates among Black mothers and their offspring, higher levels of malnutrition and obesity among Black children and adolescents, and a higher burden of chronic disease and lower life expectancy for Black adults. Although nutrition is only one of many factors that influence human health and well-being across the life continuum, a growing body of research continues to demonstrate that consuming a healthy dietary pattern is one of the most dominant factors associated with increased longevity, improved mental health, improved immunity, and decreased risk for obesity and chronic disease. Unfortunately, large percentages of Black Americans tend to consume inadequate amounts of several essential nutrients such as vitamin A, vitamin D, calcium, and magnesium; and simultaneously consume excessive amounts of fast foods and sugar-sweetened beverages to a greater degree than other racial/ethnic groups. Therefore, strategies that can help improve dietary patterns for Black Americans could make up a major public health opportunity for reducing nutrition-related diseases and health disparities across the life course. A key intervention strategy to improve diet quality among Black Americans is to focus on increasing the intake of nutrient-rich dairy foods, which are significantly underconsumed by most Black Americans. Compared to other food group, dairy foods are some of the most accessible and affordable sources of essential nutrients like vitamin A, D, and B12, calcium, magnesium, potassium, selenium, and zinc in the food supply, as well as being some of the primary sources of several health-promoting bioactive compounds, including polar lipids, bioactive proteins and peptides, oligosaccharides, and live and active cultures in fermented products. Given the complex relationships that many Black Americans have with dairy foods, due to issues with lactose intolerance, and/or negative perceptions about the health effects of dairy foods, there is still a need to examine the role that dairy foods play in the health and well-being of Black Americans of all ages and life stages. Therefore, the National Medical Association and its partners have produced multiple reports on the value of including adequate dairy in the diet of Black Americans. This present summary paper and its associated series of evidence reviews provide an examination of an immense amount of research focused on dairy intake and health outcomes, with an emphasis on evidence-based strategies for improving the health of Black Americans. Overall, the findings and conclusions from this body of research continue to indicate that higher dairy intake is associated with reduced risk for many of the most commonly occurring deficiencies and diseases impacting each life stage, and that Black Americans would receive significantly greater health benefits by increasing their daily dairy intake levels to meet the national recommendations than they would from continuing to fall short of these recommendations. However, these recommendations must be considered with appropriate context and nuance as the intake of different dairy products can have different impacts on health outcomes. For instance, vitamin D fortified dairy products and fermented dairy products like yogurt - which are low in lactose and rich in live and active cultures - tend to show the greatest benefits for improved health. Importantly, there are significant limitations to these research findings for Black Americans, especially as they relate to reproductive and child health, since most of the research on dairy intake and health has failed to include adequate representation of Black populations or to sufficiently address the role of dairy intake during the most vulnerable life stages, such as pregancy, lactation, fetal development, early childhood, and older age. This population and these life stages require considerably more research and policy attention if health equity is ever to be achieved for Black Americans. Sharing and applying the learnings from this summary paper and its associated series of evidence reviews will help inform and empower nutrition and health practitioners to provide more evidence-based dietary recommendations for improving the health and well-being of Black Americans across the life course.

BACKGROUND:Early studies showed promise of combined anti-epidermal growth factor receptor (EGFR) plus anti-vascular endothelial growth factor (VEGF) antibodies for advanced colorectal cancer (CRC), yet this was later rejected as toxic and ineffective in studies not selected for RAS status. We studied advanced KRAS wild-type CRC, as second-line treatment, using irinotecan-cetuximab with or without the anti-VEGF receptor antibody ramucirumab. METHODS:Patients with 1 prior regimen including fluoropyrimidine, oxaliplatin, and bevacizumab, with KRAS wild-type tumors were stratified by Eastern Cooperative Oncology Group Performance Score, time since last chemotherapy, and progression on oxaliplatin to irinotecan-cetuximab (IC) (180 mg/m2 and 500 mg/m2 every 2 weeks) vs modified ICR (irinotecan-cetuximab with ramucirumab 150 mg/m2 and 400 mg/m2 plus 6 mg/kg, respectively). A total of 102 patients were compared for progression-free survival (PFS) as primary endpoint (85% power for 70% improvement in median PFS from 4.5 to 7.65 months). RESULTS:Of the 102 enrolled, 44 treated with irinotecan-cetuximab and 45 with modified ramucirumab were evaluable. Median PFS was 6.0 months vs 9.2 months, respectively (hazard ratio = 0.75, P = .07; statistically significant by study design for P < .128). Response rate was 23% vs 36% (P = .27), and disease-control rate was 52% vs 73% (P = .05). Grade 3 or higher toxicity was equivalent. Overall survival was not significantly different at approximately 19 months. CONCLUSION:Previous phase 3 trials without RAS genotyping rejected combining anti-epidermal growth factor receptor and anti-VEGF drugs. In this randomized multicenter phase 2 study for KRAS wild-type CRC (all previously bevacizumab treated), the addition of ramucirumab to irinotecan and cetuximab improved PFS and disease control rate, showing the combination is feasible and effective. Further, phase 3 trials with appropriate patient-selection are required. (NCT01079780).

Objective: Health disparities in lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+), or sexual and gender minority (SGM) people are known. SGM people have higher cancer risk, but lower rates of screenings, resulting in a higher likelihood of late-stage disease. This study evaluates medical students' clinical cultural awareness in cancer care of SGM patients to identify gaps in education. Methods: This was a cross-sectional survey distributed to medical students at a academic center. There were 38 questions on demographics, attitudes, and knowledge of SGM topics. Descriptive statistics were used for demographic information and stratified analyses assessed responses by demographic subgroups. Results: There were 238 responses from 1145 students (response rate = 20.7 %). Of the responders, 91.2 % and 79 % were comfortable treating lesbian, gay, bisexual (LGB) and transgender patients respectively. Only 28.6 % and 21.8 % were confident treating LGB and transgender patients respectively after taking the survey. 91.2 % of students were interested receiving education regarding SGM health needs. Conclusion: While most medical students are comfortable treating LGBTQ+ patients, most are not confident in their knowledge. This difference is most profound in knowledge of transgender patients. Practice implications: Schools must provide more education in SGM topics to improve student knowledge to produce competent providers.

Supplementary Table S5: Association between clinicopathological variables and treatment discontinuation due to AIMSS.

AbstractPurpose: Aromatase inhibitor (AI)–associated musculoskeletal symptoms (AIMSS) are common and frequently lead to AI discontinuation. SNPs in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate the association between 10 SNPs and AI discontinuation due to AIMSS. Patients and Methods: Postmenopausal women with stage I to III hormone receptor–positive breast cancer received anastrozole 1 mg daily and completed patient-reported outcome measures to assess AIMSS (Stanford Health Assessment Questionnaire) at baseline, 3, 6, 9, and 12 months. We estimated that 40% of participants would develop AIMSS and 25% would discontinue AI treatment within 12 months. Enrollment of 1,000 women with a fixed number per racial stratum provided 80% power to detect an effect size of 1.5 to 4. SNPs were found in ESR1 (rs2234693, rs2347868, and rs9340835), CYP19A1 (rs1062033 and rs4646), TCL1A (rs11849538, rs2369049, rs7158782, and rs7159713), and HTR2A (rs2296972). Results: Of the 970 evaluable women, 43% developed AIMSS and 12% discontinued AI therapy within 12 months. Although more Black and Asian women developed AIMSS than White women (49% vs. 39%, P = 0.017; 50% vs. 39%, P = 0.004, respectively), the AI discontinuation rates were similar across groups. None of the SNPs were significantly associated with AIMSS or AI discontinuation in the overall population or in distinct cohorts. The OR for rs2296972 (HTR2A) approached significance for developing AIMSS. Conclusions: We were unable to prospectively validate candidate SNPs previously associated with AI discontinuation due to AIMSS. Future analyses will explore additional genetic markers, patient-reported outcome predictors of AIMSS, and differences by race.

PURPOSE:Black women experience higher rates of taxane-induced peripheral neuropathy (TIPN) compared with White women when receiving adjuvant once weekly paclitaxel for early-stage breast cancer, leading to more dose reductions and higher recurrence rates. EAZ171 aimed to prospectively validate germline predictors of TIPN and compare rates of TIPN and dose reductions in Black women receiving (neo)adjuvant once weekly paclitaxel and once every 3 weeks docetaxel for early-stage breast cancer. METHODS:Women with early-stage breast cancer who self-identified as Black and had intended to receive (neo)adjuvant once weekly paclitaxel or once every 3 weeks docetaxel were eligible, with planned accrual to 120 patients in each arm. Genotyping was performed to determine germline neuropathy risk. Grade 2-4 TIPN by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 was compared between high- versus low-risk genotypes and between once weekly paclitaxel versus once every 3 weeks docetaxel within 1 year. Patient-rated TIPN and patient-reported outcomes were compared using patient-reported outcome (PRO)-CTCAE and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity. RESULTS:Two hundred and forty of 249 enrolled patients had genotype data, and 91 of 117 (77.8%) receiving once weekly paclitaxel and 87 of 118 (73.7%) receiving once every 3 weeks docetaxel were classified as high-risk. Physician-reported grade 2-4 TIPN was not significantly different in high- versus low-risk genotype groups with once weekly paclitaxel (47% v 35%; P = .27) or with once every 3 weeks docetaxel (28% v 19%; P = .47). Grade 2-4 TIPN was significantly higher in the once weekly paclitaxel versus once every 3 weeks docetaxel arm by both physician-rated CTCAE (45% v 29%; P = .02) and PRO-CTCAE (40% v 24%; P = .03). Patients receiving once weekly paclitaxel required more dose reductions because of TIPN (28% v 9%; P < .001) or any cause (39% v 25%; P = .02). CONCLUSION:Germline variation did not predict risk of TIPN in Black women receiving (neo)adjuvant once weekly paclitaxel or once every 3 weeks docetaxel. Once weekly paclitaxel was associated with significantly more grade 2-4 TIPN and required more dose reductions than once every 3 weeks docetaxel.

Supplementary Table S6: Allele frequency and Hardy-Weinberg equilibrium test result, by patient cohort.

Abstract This review describes the barriers and challenges faced by older adults of color with cancer and highlights methods to improve their overall care. In the next decade, cancer incidence rates are expected to increase in the United States for people aged ≥65 years. A large proportion will be older adults of color who often have worse outcomes than older White patients. Many issues contribute to racial disparities in older adults, including biological factors and social determinants of health (SDOH) related to healthcare access, socioeconomic concerns, systemic racism, mistrust, and the neighborhood where a person lives. These disparities are exacerbated by age‐related challenges often experienced by older adults, such as decreased functional status, impaired cognition, high rates of comorbidities and polypharmacy, poor nutrition, and limited social support. Additionally, underrepresentation of both patients of color and older adults in cancer clinical research results in a lack of adequate data to guide the management of these patients. Use of geriatric assessments (GA) can aid providers in uncovering age‐related concerns and personalizing interventions for older patients. Research demonstrates the ability of GA‐directed care to result in fewer treatment‐related toxicities and improved quality of life, thus supporting the routine incorporation of validated GA into these patients' care. GA can be enhanced by including evaluation of SDOH, which can help healthcare providers understand and address the needs of older adults of color with cancer who face disparities related to their age and race.

INTRODUCTION:Targeted therapy has improved clinical outcomes for various types of cancer. However, their use is associated with dermatologic adverse events that impact quality of life and consistent therapies. OBJECTIVES:The US Cutaneous Oncodermatology Management (USCOM) multidisciplinary-guided algorithm for preventing and managing cutaneous targeted therapy-related adverse events provides practical recommendations for cancer patients and survivors. METHODS:The USCOM advisory board (panel) identified 6 commonly occurring cutaneous adverse events associated with targeted therapies. Practical recommendations for prevention and management were developed based on the results of a literature search, clinical expertise, and opinion. RESULTS:Acneiform rash, pruritus, xerosis, paronychia, hyperpigmentation, and hand-foot skin reaction were selected as common targeted therapy-related cutaneous adverse events. The panel provides practical steps for preventing and treating these cutaneous conditions. CONCLUSIONS:The USCOM multidisciplinary-guided algorithm is for healthcare providers treating oncology patients receiving targeted therapies. Cutaneous targeted therapy-related adverse events necessitate prompt and accurate diagnosis and multidisciplinary management that includes a dermatologist and the oncologic team, limiting disruption of cancer treatment and optimizing quality of life and treatment outcomes. J Drugs Dermatol. 2024;23:12(Suppl 1):s3-14.