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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. TPS1113-TPS1113
    Abstract: TPS1113 Background: Despite major improvement of overall survival of HER2+ MBC with effective HER2 targeted therapies, many patients experience significant toxicities and develop progressive disease during treatment. Therefore, new and more effective therapeutic options are needed. This novel approach will evaluate whether the combination of three immunotherapies in addition to trastuzumab: dendritic cell (DC) vaccination, anti-SEMA4D blocking antibody (pepinemab) and CD4+ T cell adoptive transfer can lead to improved outcomes for patients with MBC refractory to HER2-targeted agents. BC have been considered as immunologically cold which is attributed to immune evasion and suppression of host effector immune cells homing into tumor bed. Progressive loss of Th1 immunity against HER2 oncodriver correlates with poor prognosis. HER2 peptide pulsed type I dendritic cells (HER2-DC1) restored anti-HER2 CD4+ Th1 immune response and improved pathologic complete response (pCR) in HER2+ BC. Antibodies to SEMA4D have been shown to modulate the TME by increasing effector cell infiltration and reducing immunosuppression. In preclinical studies, treatment with anti-SEMA4D and HER2-DC1 in mice bearing established HER2+ tumors improved DC homing, expansion of CD4+ T cells, and complete tumor regression, compared to treatment with anti-SEMA4D or HER2-DC1 alone. Further, subsequent expansion and adoptive transfer of CD4+ T cells induced synergistic anti-tumor activity by activating CD8+ T mediated cytotoxicity. Pepinemab was well-tolerated and showed signs of anti-tumor activity in in immunotherapy-resistant and PD-L1 negative/low non-small cell lung cancer patients when combined with checkpoint inhibitor (avelumab). Methods: This open label Phase 1 study is enrolling up to 28 patients with HER2+ MBC. Patients will be treated with 6 weekly injections of dendritic cell (DC1) vaccines in combination with trastuzumab and pepinemab. We hypothesize these therapies may elicit CD4+ HER2-specific T cell responses. HER2-specific T cells will be expanded ex vivo and subsequently infused to patients following lymphodepletion with cyclophosphamide. Trastuzumab and pepinemab will be given as maintenance in addition to booster DC1 vaccines. Patients (ECOG 0,1) must have had disease progression while on trastuzumab for the treatment of HER2+ MBC and received no more than 3 lines of chemotherapy in the setting of metastatic disease. Dose escalation will consist of 3-6 patients each with increasing amounts of transferred CD4+ T cells, followed by dose expansion of 10 patients at the MTD. The primary objective is safety and tolerability; secondary objectives will include evaluation of T cell immunity and immune subsets, efficacy, PK/PD/ADA of pepinemab, and biomarker assessments. Clinical trial information: NCT05378464 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. TPS629-TPS629
    Abstract: TPS629 Background: Patients with breast cancers (BCs) harboring low expression of hormone receptors (HRs) and human epidermal growth factor receptor-2 (HER2) have poor outcomes. Results from the KEYNOTE-522 trial showed that activation of the immune system using a PD1/PD-L1-targeted approach improves outcomes of patients with these high-risk tumors. Antigen-presenting cells (eg, dendritic cells [DCs]) are pivotal for robust cytotoxic responses due to broader activation of the adaptive immune system (ie, CD4 + and CD8 + Th1) against tumor-associated antigens (ie, HER2 or HER3) expressed by high-risk BCs. Methods: DecipHER is a dose-escalation, dose-expansion phase 1 trial designed to assess the safety and the preliminary efficacy of autologous, HER2- and HER3-primed DCs in combination with KEYNOTE 522 regimen in 30 patients. Patients with clinical stage cT1cN1/2 or cT2-4cN0-2, HR 20, HER2-negative BCs are eligible. Patients with inflammatory BC cancer and uncontrolled immune mediated diseases are excluded. After collection through aphaeresis, autologous DCs will be primed ex vivo against 6 HER2 and 8 HER3 immunogenic peptides. Participants will receive alternating ultrasound-guided intratumoral HER2 and HER3 DC injections administered twice a week for 8 doses in total starting 2 weeks prior to neoadjuvant therapy with KEYNOTE 522 regimen. The dose-escalation phase of the study has 3 planned cohorts (10-20, 30-50, 80-100 million DCs) and follows a 3+3 design (maximum n=18). The 12 additional patients enrolled will be treated at the maximum tolerated dose (MTD) in the dose-expansion cohort. The MTD will be defined as the highest dose level at which 〈 2 of 6 patients experience dose-limiting toxicities (grade ≥ 3 non-hematologic, ; grade ≥ 3 hematologic toxicity thought be at least possibly related to DCs ; any grade 4 nausea, vomiting, or diarrhea [or grade 3 if duration 〉 3 days]) during the 5 weeks following treatment initiation with DCs. Secondary endpoints include the absolute risk of adverse events, clinical and pathological responses, and recurrence free survival. Tumor tissue, blood and stool samples will be collected for correlative analyses. The study is open at H. Lee Moffitt Cancer Center. Clinical trial information: NCT05504707 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    SAGE Publications ; 2021
    In:  American Journal of Hospice and Palliative Medicine® Vol. 38, No. 6 ( 2021-06), p. 671-677
    In: American Journal of Hospice and Palliative Medicine®, SAGE Publications, Vol. 38, No. 6 ( 2021-06), p. 671-677
    Abstract: Hospice and Palliative care benefits are infrequently realized by African American patients with cancer. With the increasing recognition of the critical role of early utilization of palliative services for optimal and quality patient care, it is important to acknowledge disparities and barriers to access that minority patients may face. The purpose of this paper is to discuss the status of palliative care delivery for African American patients within the structure and framework of the clinical practice guideline domains established by the National Consensus Project for Palliative Care. This perspectives paper describes the different aspects of palliative care and the interplay with African American culture. Here, we also attempt to identify the multilevel barriers (health care system and provider level) to palliative care among African Americans as a required step toward decreasing the disparities in access, coverage, utilization, and benefit of palliative care. Furthermore, this paper may serve as an educational guide for health care workers who care for African American patients with cancer.
    Type of Medium: Online Resource
    ISSN: 1049-9091 , 1938-2715
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
    detail.hit.zdb_id: 2236674-X
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  • 4
    In: Journal of Pain and Symptom Management, Elsevier BV, Vol. 60, No. 1 ( 2020-07), p. 10-19
    Type of Medium: Online Resource
    ISSN: 0885-3924
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 1500639-6
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  • 5
    In: Cancer, Wiley, Vol. 126, No. 16 ( 2020-08-15), p. 3606-3612
    Abstract: To successfully reduce high rates of oral anticancer medication nonadherence, the systems that govern drug policies and drug supply, provider reimbursement, prescribing biases, and adherence monitoring must be identified and addressed. This commentary highlights these systems and the challenges that they pose for providers and for patients to adhere to oral anticancer medication.
    Type of Medium: Online Resource
    ISSN: 0008-543X , 1097-0142
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 1479932-7
    detail.hit.zdb_id: 2599218-1
    detail.hit.zdb_id: 2594979-2
    detail.hit.zdb_id: 1429-1
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  • 6
    Online Resource
    Online Resource
    Mary Ann Liebert Inc ; 2021
    In:  Journal of Palliative Medicine Vol. 24, No. 11 ( 2021-11-01), p. 1714-1720
    In: Journal of Palliative Medicine, Mary Ann Liebert Inc, Vol. 24, No. 11 ( 2021-11-01), p. 1714-1720
    Type of Medium: Online Resource
    ISSN: 1096-6218 , 1557-7740
    Language: English
    Publisher: Mary Ann Liebert Inc
    Publication Date: 2021
    detail.hit.zdb_id: 2030890-5
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  • 7
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 29, No. 6_Supplement_2 ( 2020-06-01), p. A136-A136
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 29, No. 6_Supplement_2 ( 2020-06-01), p. A136-A136
    Abstract: Adjuvant endocrine therapy (AET) is associated with significant improvements in disease-free and overall survival for patients with hormone receptor positive (HR+) breast cancer and guidelines recommend initiation of AET within 12 months of diagnosis. Black women with HR+ breast cancer have poorer overall survival than their white counterparts and breast cancer is the leading cause of cancer death for Hispanic women. We aim to describe the relationship between race/ethnicity and prolonged time to AET and identify other predictors of delayed AET. This is a retrospective, population-based cohort study using the National Cancer Database, which captures more than 70% of incident cancer cases in the US. We examined 249,761 women who were diagnosed with invasive stage IB to III, HR+, HER2- breast cancer between 2004 and 2014, had cancer-directed surgery, and who were prescribed AET. Time to AET was defined as time from breast cancer diagnosis to initiation of AET. Delayed AET was defined as more than 12 months from date of breast cancer diagnosis. Multivariable logistic regression models were used to identify predictors of delayed AET. Eighty percent (186,197) of women were white, ~10% (22,841) were black, and 5% (12,101) were Hispanic. Among all patients, mean age at diagnosis was 58.5 years, 29% were diagnosed with stage IB, 43% with stage II, and 27% with stage III cancer, and median time to initiation of AET was 6.1 months. Mean age of black and Hispanic women at diagnosis was 56.4 and 53.9 years respectively, compared to 59.2 years for white women. Fourteen and 20% of black and Hispanic patients were insured by Medicaid, respectively, versus 4.4% of white women. Black and Hispanic women had almost twice the odds of delayed time from diagnosis to surgery compared to white women (OR 1.78, 95% 1.73-1.83 and OR 1.93, 95% CI 1.86-2.01, respectively). In univariate analyses, factors associated with delayed AET were black and Hispanic race/ethnicity, being uninsured or having Medicaid, older age (categorized as & gt; 70 years¬), higher tumor grade or stage, receipt of chemotherapy or radiation therapy, and delayed time to surgery or chemotherapy. Our final multivariable model adjusted for these significant factors, as well as comorbidities, urban/rural residence, and income and education (based on zip-code). In this model, being uninsured was no longer positively associated with delay in AET. Black patients had a 19% higher odds of delayed AET (OR 1.19, 95% CI 1.14-1.24) and Hispanic patients had 57% higher odds of delay compared to their white counterparts (OR 1.57, 95% CI 1.49-1.65). There are racial disparities in the quality of breast cancer care provided to patients in this study. Being of black or Hispanic race/ethnicity was associated with increased odds of delayed time to initiating AET beyond the recommended time frame of 12 months after diagnosis. Medicaid enrollment was also a predictor of delayed time to AET. Future efforts should be focused on improving delivery of quality breast cancer care measures to vulnerable populations. Citation Format: Kimberley T Lee, Vered Stearns, Lisa K Jacobs. Racial disparities in delayed initiation of adjuvant endocrine therapy among patients with breast cancer [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A136.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 8
    In: Future Oncology, Future Medicine Ltd, Vol. 18, No. 21 ( 2022-07), p. 2667-2682
    Abstract: Plain language summary Breast cancer is frequently diagnosed early, at a stage when patients can be cured. However, some patients have breast cancers (tumors) with a high risk of recurrence. When cancers come back, a cure is often not possible. This study looks at multiple high-risk tumor features and the risk of cancer returning, in the most common breast cancer type, known as hormone receptor-positive, HER2-negative breast cancer. In patients with high-risk tumors, breast cancer returned in about 11.9% of patients within 2 years and in 29.8% of patients at 5 years. The risk of recurrence or death was three-times higher in patients with high-risk tumors compared to patients with nonhigh-risk tumors. These results suggest better treatments are needed to prevent breast cancers from coming back in patients at high risk of recurrence.
    Type of Medium: Online Resource
    ISSN: 1479-6694 , 1744-8301
    Language: English
    Publisher: Future Medicine Ltd
    Publication Date: 2022
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  • 9
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 32, No. 1_Supplement ( 2023-01-01), p. B086-B086
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 32, No. 1_Supplement ( 2023-01-01), p. B086-B086
    Abstract: Post-operative or adjuvant endocrine therapy (AET) is the mainstay of treatment for hormone receptor-positive (HR+) breast cancer. When taken daily for 5-to-10 years, AET improves the time to disease recurrence and overall survival rates. However, past work has shown that Black women are less likely to begin prescribed AET treatments and less likely to take these medications as directed, often discontinuing treatment early. For hormone receptor-positive (HR+) breast cancer, rates of death from breast cancer are higher than those of similar White women. This study investigates the patient-, provider-, and practice-level barriers to AET initiation and adherence faced by Black women with the ultimate goal of developing an intervention to address these barriers. This study consists of qualitative semi-structured interviews with two populations, Black breast cancer survivors with HR+ breast cancer who were prescribed AET and cancer care providers (including medical doctors and advance-practice providers). All participants were recruited from the same comprehensive cancer center with a dedicated breast cancer clinic. Data collection is ongoing; thus far, the sample includes fifteen interviews with breast cancer survivors and nine with providers. Participants were asked about the barriers to care they (or their patients) face, their (or their patients’) perception of AET, and their views of possible interventions to improve clinical practices related to AET initiation and adherence. Preliminary findings include differences in perceived barriers to care between Black women and their providers. Providers understood barriers to AET initiation and adherence as minimal compared to other treatments, in terms of cost, toxicity, and burden of care. Meanwhile, patients understood the cost of the treatment as very high, largely due to side-effect. While the price of the medications were not a common barrier, the side effects (including brain fog, bone aches, fatigue, and depression) impact patients’ interpersonal relationships, employment, and/or ability to perform care work for family members, were seen as a heavy burden. In addition, patient interviews showed a need for higher quality education regarding how AET therapy works and its importance in preventing recurrence. While providers described the myriad ways in which they educate their patients about AET and its importance in breast cancer care, patients interviewed described gaps in their knowledge related to how AET works and why it is an essential aspect of their care. These findings point to a need for reframing barriers to breast cancer care for providers and the implementation of new clinical procedures to address and rectify racial disparities in AET use. Citation Format: Hayden J. Fulton, Dannelle R. Charles, Kimberley T. Lee. Barriers to use of adjuvant endocrine therapy among Black women with breast cancer: A qualitative investigation [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B086.
    Type of Medium: Online Resource
    ISSN: 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 10
    Online Resource
    Online Resource
    Harborside Press, LLC ; 2021
    In:  Journal of the National Comprehensive Cancer Network Vol. 19, No. 3.5 ( 2021-03-20), p. HSR21-058-
    In: Journal of the National Comprehensive Cancer Network, Harborside Press, LLC, Vol. 19, No. 3.5 ( 2021-03-20), p. HSR21-058-
    Type of Medium: Online Resource
    ISSN: 1540-1405 , 1540-1413
    Language: Unknown
    Publisher: Harborside Press, LLC
    Publication Date: 2021
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