Dronca, Roxana

Abstract Intro: Compared to white men, Black men bear the highest burden of prostate cancer, experiencing a higher incidence and mortality rate, and poorer survivorship outcomes. Although prioritized, survivorship and quality of life (QOL) are under-studied in the fight against prostate cancer disparities. To address this issue, clinicians, researchers, and community advocates have formed the Inclusive Cancer Care Research Equity (iCCaRE) Consortium for Black Men. iCCaRE’s goal is to advance the science and practice of survivorship focused on the needs of Black men and their loved ones affected by prostate cancer. Methods: We developed a survivorship care plan (SCP) tailored to the whole person's needs. IRB-approved qualitative methods to preliminarily gain evaluation and guidance on the SCP. The SCP presented content in the following areas: diagnosis and treatment, follow-up care/surveillance, family history, care team, major co-morbidities, symptoms and quality of life, survivorship concerns, and health advisories. Results: 23 Black prostate cancer survivors (PCS) participated and provided feedback on the SCP Mean age was 64 years. PCS diagnosed between 2018-2023 between stages 1-4. The Majority of PCS were provided information for follow-up and side effects. But none had received a comprehensive SCP All agreed that the SCP would contribute to enhancing cancer knowledge, patient activation, and shared decision, and their QOL, if the SCP was obtained. A survivor noted “having inspirational quotes throughout the SCP is important”. An unforeseen consequence to the interviews was the emotional release for the men, justifying the need for the SCP and an expansion of its scope. Domains that the men wanted more contents were social support, sexuality, masculinity, and maintaining a healthy lifestyle. All PCS understood the value of having trusted family and friends to bear the burden of the disease despite some not having a solid support system. PCS emphasized the role of family support stating, “my wife and children helped me stay positive”. Another critical lifestyle component that survivors mentioned was their sexuality and how it directly reflects their masculinity. Although PCS adapted to other forms of intimacy like couples’ activities and stronger communication with their partners, majority of men struggle with adapting to their sexual performance. A quote by a survivor encompasses the mindset expressed by many of the men fear “Like a track star in his prime who can’t run anymore”. Erectile Dysfunction can lead to fear and anxiety among survivors, ultimately affecting QOL. Lastly, PCS wanted more options to stay fit and healthy. Further research and resources are needed to address survivor concerns in this area. Discussion: Overall, PCS have acknowledged that the SCP can assist them in these areas of concern, but more research is required. Life after prostate cancer treatment is an ongoing process; while some survivors cope better than others, it is evident a need for more information and guidance is not being provided to all those affected. Citation Format: James Morrison, Kimlin Ashing, Gaole Song, John McCall, Timethia J. Bonner, Che Ngufor, Getachew A. Dagne, Arnold Merriweather, Ewan Cobran, Cassandra N. Moore, Fornati Bedell, Rotimi Oladapo, Floyd B. Willis, JoAnne S. Oliver, Ernie Kaninjing, Roxana Dronca, Folakemi T. Odedina. iCCaRE qualitative interviews for Black prostate cancer survivors and quality of life [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C042.

AbstractThe challenge of disease relapsed/refractory (R/R) remains a therapeutic hurdle in chimeric antigen receptor (CAR) T‐cell therapy, especially for hematological diseases, with chronic lymphocytic leukemia (CLL) being particularly resistant to CD19 CAR T cells. Currently, there is no approved CAR T‐cell therapy for CLL patients. In this study, we aimed to address this unmet medical need by choosing the B‐cell activating factor receptor (BAFF‐R) as a promising target for CAR design against CLL. BAFF‐R is essential for B‐cell survival and is consistently expressed on CLL tumors. Our research discovered that BAFF‐R CAR T‐cell therapy exerted the cytotoxic effects on both CLL cell lines and primary B cells derived from CLL patients. In addition, the CAR T cells exhibited cytotoxicity against CD19‐knockout CLL cells that are resistant to CD19 CAR T therapy. Furthermore, we were able to generate BAFF‐R CAR T cells from small blood samples collected from CLL patients and then demonstrated the cytotoxic effects of these patient‐derived CAR T cells against autologous tumor cells. Given these promising results, BAFF‐R CAR T‐cell therapy has the potential to meet the long‐standing need for an effective treatment on CLL patients.

Melanoma is the deadliest form of skin cancer. The median age at diagnosis is 66. While most patients are treated with immunotherapy, the use of targeted therapy is a valid alternative for patients whose tumors harbor a BRAF or c-KIT driver mutation. These agents, while effective, come with a variety of side effects which limit their use, especially in older patients. We sought to assess the efficacy and toxicity of these agents in older melanoma patients. Melanoma patients over 65 treated with BRAF/MEK or c-KIT inhibitors were retrospectively identified, and their data were analyzed for treatment efficacy and toxicity. All data were compared using the Chi-square test for categorical comparisons and the Kruskal–Wallis method for median comparisons. One hundred and sixteen patients were identified. One hundred and six patients were treated with BRAF/MEK inhibitors. The assessed response rate (RR) was 83% and was comparable across different subgroups, including advanced line patients and those with a more aggressive disease. The median progression free survival (PFS) was 7.9 months, and the median overall survival (OS) was 15.7 months. Twenty-seven percent experienced grade 3–4 toxicity leading to a 24% treatment discontinuation rate. Another 10 patients were treated with the c-KIT inhibitor imatinib, for whom the assessed RR was 55%. The median PFS was 4.3 months, and the median OS was 22.6 months. Forty percent needed dose reductions, yet none had to stop treatment due to adverse effects. The use of targeted therapy in older patients is effective yet challenging due to toxicity. Deploying mitigation strategies can help maximizing their usefulness.

The NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous ) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.

e23270 Background: Melanoma is the most lethal form of skin cancer which have seen drastic improvement in patient survival over the last decade. BRAF is the most common driver mutation in melanoma, seen in ≈50% of all patients (≈30% of patients > 65). The use of BRAF & MEK inhibitors yields high response rates, though it is limited by toxicity and development of acquired resistance. Acknowledging these limitations, we aimed at assessing the efficacy and toxicity of these agents in melanoma patients > 65. Methods: We identified electronic medical records of all melanoma patients > 65 that were treated with BRAF & MEK inhibitors at our institution over the years 2017-2023. Data was retrospectively collected including demographics, disease characteristics, treatment given, response patterns and toxicity. Results: 106 patients were identified. The median age was 71 (65-89), 55% were males. The median follow up was 28.9 months. 32 (30%) patients were treated at first line, 58 (55%) at second line and 16 (15%) at third line. 88 (83%) evaluable patients received treatment for unresectable/metastatic disease of which 84% had an objective response (60% partial response, 24% complete response). Response rate (RR) was 82%, 85% and 87% for first, second and third line respectively. RR was 86% for patients with an increased serum lactate dehydrogenase. 33% of patients had active central nervous system (CNS) metastases at treatment initiation, for whom the systemic RR was 80% and the CNS RR was 39%. The median progression free survival (PFS) was 7.9 months, with a PFS of 6, 8.3 and 13.4 months for first, second and third line respectively. The median PFS was 5.7 months for patients with active CNS disease. The median overall survival (OS) from treatment initiation was 15.7 months (12.5, 14.5, 31.9 for first, second & third line respectively). The median OS for patients with CNS disease was 9.8 months. 16 patients were treated in the adjuvant setting, of which 6 (37%) finished treatment as planned, 3 stopped due to disease progression (19%) and 6 stopped due to toxicity (37%). 88% of patients experienced adverse events (AEs) of any grade, with 27% having grade 3-4 toxicity. There were no grade 5 toxicities reported. 36% of patients experienced one AE, while 52% experienced two or more. 21% of patients stopped treatment due to toxicity, 28% needed a dose reduction and 20% changed to different BRAF/MEK inhibitors. 10% of patients needed systemic corticosteroids to treat AEs. The most common toxicities seen were fever (30%), fatigue (30%), skin rash (22%), elevated liver function tests (20%), arthralgia/myalgia (15%), nausea (14%) and diarrhea (11%). 7% had decrease in cardiac ejection fraction with one grade 3 leading to treatment discontinuation. Conclusions: Treatment with BRAF & MEK inhibitors is challenging in older patients, with a high prevalence of toxicity leading to treatment modifications and discontinuation. Efficacy seems to be the same as in the general population.

Abstract Background: The prognosis of patients with MM with CNS mets is poor. E6201 is an intravenous (IV) MEK inhibitor with activity against BRAF V600-mutated MM cell lines, including MAPK resistance alteration. A previous phase I trial demonstrated activity of E6201 in BRAF V600E mutated MM with a Maximal Tolerated Dose of 320mg/m2 given IV once a week x 3 weeks q 28 days. 2/23 (8.7%) of patients had a PR, 8/23 (34.8%) had SD. Two patients with MM and brain mets achieved near-CR which led to preclinical studies that demonstrated E6201 is unaffected by P-gp and BCRP transport and achieved higher brain to blood concentration (266%).In this trial, patients with BRAF mutation + MM with brain mets, single agent E6201 given at 320mg/m2 twice weekly x 3 weeks q 28 days was determined to be safe. One patient had CNS SD and a PR in lung mets, and a second patient achieved CNS stable disease and CR in a leg melanotic lesion. The drug was well-tolerated with one reversible AE thrombocytopenia (Gr 2). The final review showed intracranial response of SD in 2/4 (50%) patients and systemic SD in 3/4 (75%) patients. Methods: We are currently accruing to the dose escalation cohort of E6201 with dabrafenib 150 mg twice daily orally (n=up to 22 evaluable patients). E6201 is administered IV at 320mg/m2 twice weekly for 3 weeks every 28 days. Patients must have stage IV melanoma with BRAF mutation with at least one active lesion in the brain. Prior local therapy is allowed if done at least 3 weeks prior to cycle 1. Participants must be on a stable dose of steroids for at least 7 days and have an ECOG <!–=2. The study allows one prior BRAF/MEK inhibitor therapy. The primary objectives are to determine the MTD of E6201 when combined with dabrafenib and the response rate of brain mets. The secondary objectives include duration of response, extracranial response, progression free survival, overall survival, and impact of BRAF mutation subtype and safety of the combination. Clinicaltrials.gov: NCT05388877 References:1.Gampa G, et al. Brain distribution of a novel MEK inhibitor E6201: implications in the treatment of melanoma brain metastases. 2018. Drug Metab Dispos.2.Tibes R et al. Safety, pharmacokinetics, and preliminary efficacy of E6201 in patients with advanced solid tumors, including melanoma: results of a phase I study. 2018. Brit J of Cancer. 3.Babiker Gm et al, E6201, an intravenous MEK1 inhibitor, achieves an exceptional response in BRAF V600E mutated metastatic malignant melanoma with brain metastases. 2018. Inv New Drugs4.Gampa G, Kim M, Cook-Rostie N, Laramy JK, Sarkaria JN, Paradiso L, DePalatis L, Elmquist WF. Brain distribution of a novel MEK inhibitor E6201: Implications in the treatment of melanoma brain metastases. 2018. Drug Met Disp.–> Citation Format: Mahesh Seetharam, Roxana Dronca, Arkadiusz Z. Dudek, Garth Nelson, Matthew Block, Skylar Starling, Amber Baskin, Renee Bradshaw, Courtney Nelson, Kylee Andrews, Alisha Birgin, Cristina Watson, Yiyi Yan, Daruka Mahadevan, Svetomir Markovic, Tom Myers, Linda Paradiso, Hani Babiker. Phase 1 trial of MEK1 inhibitor E6201 plus dabrafenib in patients (pts) with BRAF V600-mutated metastatic melanoma (MM) with central nervous system (CNS) metastases (mets) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT157.

Abstract Background: Sub-Saharan African Immigrants (SSAI) represent one of the fastest-growing segments of the immigrant population in the United States (US). Between 2010 and 2018, the SSAI population in the US increased by 53%, significantly outpacing the 12% growth rate for the overall foreign-born population in the US during that time frame. Despite these growing numbers, little is published about the extent to which SSAIs adapt to health behaviors more common in the US or remain immersed in the values, beliefs and practices reflective of their country of origin. Importantly, no study has comprehensively examined the Social Determinants of Health (SDOH) among this population relative to their migration experiences and their influence on health-seeking behaviors and decision-making regarding prostate cancer care and treatment options. Methods: This qualitative study employed grounded theory and the social determinants of migrant heath framework to better understand the needs of SSAI prostate cancer survivors in the United States and how to effectively support these survivors. In-depth interviews were conducted with 8 survivors who live in the states of Florida and Minnesota. Findings: Some participants reported limited access to care and financial challenges paying for drugs. In terms of coping with diagnosis and treatment, most of the participants relied on their faith, a positive outlook about survivorship and support of family members. Some participants relied on the coaching and support of a loved one who experienced prostate cancer in the past. Erectile dysfunction severely impacted the sexual life of most participants as they experienced difficulty getting an erection. Conclusion: Participants expressed the benefit of belonging to support groups with other survivors for social and emotional support. As the number of immigrants from sub-Saharan continue to rise, so too will the demand for culturally tailored care to address and reduce disparities in survivorship among this sub-population. Citation Format: Ernest Kaninjing, Gladys Asiedu, Kaitlin Van Voorhis, Mary Ellen Young, Ebenezer Erefah, Emmanuel Agboola, Folakemi Odedina, Roxana Dronca, Kimlin Ashing, Solomon Rotimi, Che Ngufor, Arnola Merriweather, John McCall, Anthony Hill. Social determinants of migrant health factors impacting prostate cancer care and survivorship among sub-Saharan African immigrant men diagnosed with prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1310.

Abstract Introduction: Black men have the highest prostate cancer (CaP) mortality rates. The reason for this disparity is multifaceted, including the barriers that they face at the individual, provider, and health system levels. To address these challenges the iCCaRE for Black Men Consortium uses a multi-level approach to disseminating CaP information. This approach is rooted in research which shows that Black men prefer to receive information through multi-media channels tailored to their needs. In addition, studies have reported that CaP survivors were viewed as credible sources of information. This presentation reports on how iCCaRE Consortium is bridging the digital divide in minoritized communities to disseminate CaP information in a way that is meaningful to the community. Methodology: iCCaRE uses a multimedia method to reach Black men. This includes twitter post, Facebook, YouTube, ecancer and community lunch and learns. In addition to social media, we have partnered with LitTV Network, a locally owned digital TV platform, on which we have iCCaRE TV. On Lit TV network we have the ability to reach 11,000 homes in our catchment area. Furthermore, the consortium has produced informational flyers that are disseminated at outreach events and at the American Legion Post 197. On the twitter page the consortium post: (1) 2 scientific publications per day authored by members of the consortium, (2) 2 weekly “Did You Know” facts about prostate cancer with sources attached, (3) 2 weekly url post sharing a link to a video from the iCCaRE consortium YouTube page and (4) clips of CaP survivors sharing their experiences. On the YouTube page we currently have: videos series of a CaP survivor who is also a physician scientist, interview series with MPIs and members of the consortium, CaP survivor series including a barbershop interview with a survivor. Results: The iCCaRE Consortium multimedia efforts have a global reach, in less than a year we have gained 102 twitter followers. On average the twitter page receives 8,700 impressions during the CaP awareness month in September the twitter page garnered over 14,000 impressions. Our videos on the ecancer platform have a combined global view of 341 representing countries such as the United States, Nigeria, Cameroon, United Kingdom, Macedonia, and Mexico. The American Legion Post 197 in North Jacksonville has served a cumulative of 229 people through outreach and educational event called lunch and learns. Our YouTube channel has had almost 100 views in its first month of being active. Conclusion: Using a multi-level approach to reduce the burden of CaP for Black men is vitally important; without such efforts the disparate thread in mortality will continue to persist. Meeting Black men through the mediums they use for gathering health information removes barriers, increases access and will aid in the fight against CaP for Black Men. Citation Format: Vinessa Gordon, Folakemi Odedina, Kimling Tam Ashing, Arnold Merriweather, Roxana Dronca, Che Ngufor, Solomon Rotimi, Ernest Kaninjing, Abimbola Odedina, John McCall, Anthony Hill, Ayinde Yahaya, Emmanuel Agboola. Fighting prostate cancer with a multimedia approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 818.

Abstract The objective of our study is to evaluate the feasibility, acceptance, and impact of patient-centered home care (PCHC) on patient reported outcomes (PROs) and health-related quality of life (HQoL) of black men with advanced prostate cancer (CaP). Meeting patients where they are and offering treatment in or closer to their homes reduce psychological distress and increase treatment compliance, especially for disadvantaged patients in rural areas, those on low incomes, with poor access to transport, elderly and people with disabilities. In 2023, Mayo Clinic has developed the Cancer Care Beyond Walls (CCBW) program, a cancer care delivery model that integrates virtual with in facility treatment and provides a package of care to support administration of cancer-directed therapy (chemotherapy, immunotherapy, hormonal therapy) and/or supportive care in the patients’ homes. Our study will assess if patients and families are comfortable with cancer therapy at home, what factors influences their decision, and use this data to inform our understanding of the proportion of the black men with advanced CaP who would be willing to receive and would benefit from this level of care at home. Patients with advanced CaP from our practice requiring active anti-cancer therapy are administered a brief questionnaire regarding preference for location of therapy at the infusion center or in the home, with perceived difficulties and advantages of each approach. A focus group session with prostate cancer survivor advocates is also conducted to capture patients’ thoughts, feelings, attitudes, and questions towards cancer treatments being administered at home versus a hospital setting. In addition, we are conducting an observational study of 20 patients with advanced prostate cancer receiving supportive care/symptom management and/or anti-cancer therapy in the home as part of the Mayo Clinic CCBW Program to assess the safety of cancer directed therapy when administered at home by a home health provider with remote patient monitoring and command center support, and establish the impact of home cancer treatment administration on patient-reported function and global health/quality of life, patient-reported symptoms, clinical outcomes, and cost of care. Successful completion of the project will deliver data on patient understanding and acceptability of cancer care at home, strategies for overcoming barriers to care for underserved communities, and the foundation from which we discover, translate and apply new knowledge in administering personalized care to vulnerable populations. Citation Format: Roxana S. Dronca, Folakemi Odedina, Che Ngufor, Kimlin Ashing, Ernest Kaninjing, Solomon Rotimi. Feasibility of patient-centered home care (PCHC) to reduce disparities in high-risk black men with advanced prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 819.

Abstract Background: The point of prostate cancer (CaP) diagnosis (PPCD) instantly leads to a life changing experience for Black men, with diverse emotional reactions that includes fear, denial, overwhelmingness, cancer fatalism etc. Black men diagnosed with CaP expressed several needs at the PPCD, including time to reflect on the diagnosis, being comfortable, emotional support, psycho-oncology support and social determinants of health (SDOH) navigation. Given that Black men are diverse in terms of their needs at the PPCD, precision intervention is needed to support them. Aim: The aim was to develop, implement, and establish the acceptance and usability of a Virtual Reality Assistant (ViRA) that will provide precision intervention tailored to the needs of Black men at the PPCD. This study is one of the five iCCaRE for Black Men projects focused on survivorship care. Methodology: The development of the ViRA was guided by CaP survivors through qualitative study. Reflective, analytic, and interpretive memos were used to generate action plans for the development of the ViRA. Based on a comprehensive PPCD ViRA intervention guide created by the team, the ViRA prototype was developed with mobile immersive technologies that integrated SDOH navigation, standard CaP psycho-oncology support and emotional support. The goal was to have the intervention personalized to everyone based on participant-provided information. Alpha testing of the ViRA is ongoing and will be completed on November 20, 2023. Participants are three prostate cancer survivors and three clinicians. The assessments will confirm the accuracy of the ViRA predictions and the functionality of the ViRA. Results: We developed the ViRA SDOH screening and navigation tool to identify participants’ needs and appropriately connect them with relevant support services and resources in their communities. The emotional support intervention was based on four CaP survivors as virtual reality avatars, providing empathetic rapport through self-disclosure and sharing of survivorship stories in different settings (home, clinic, barbershop etc). The psycho-oncology support intervention was developed with the guidance of a psycho-oncologist, with her avatar providing psychoeducation about the PPCD experience, reify and concretize the PPCD experience, and foster hope using the basic tenets of Problem-Solving Therapy. The results of the alpha testing and the modified ViRA will be presented during the conference. Conclusion: Meeting the needs of Black men at the PPCD requires a personalized and decentralized approach, which would allow Black men to access support anywhere. The presentation will unveil the iCCaRE ViRA, a smart and connected personalized AR-enabled intervention that will deliver SDOH navigation, CaP psycho-oncology support and emotional support tailored to the needs of Black men. Citation Format: Folakemi T. Odedina, Che Ngufor, Arnold Merriweather, Deidre Pereira, Roxana Dronca, Ernest Kaninjing, Kimlin Ashing, Solomon Rotimi, Vinessa Gordon, iCCaRE for Black Men Consortium. Connecting Black men to point of prostate cancer diagnosis (PPCD) support using precision intervention based on Virtual Reality Assistant (ViRA) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2230.