Cancer Clinical Trials Research Articles

Unleashing patient voices: empowering adverse event assessment with complete patient-reported outcomes.

The 124-item patient reported-outcome common terminology criteria for adverse events (PRO-CTCAE) questionnaire, assessing 78 symptoms, is widely used in cancer clinical trials to identify side effects. However, its regular use in routine cancer care is rarely reported. We aimed to investigate the feasibility of weekly PRO-CTCAE completion over 9 weeks in a prospective study with 30 patients with cancer undergoing chemotherapy. Participants were asked to complete electronic surveys with reminders, but no feedback or incentives. Only 136 (50%) of the planned 270 time points at which a PRO-CTCAE self-report was expected were completed, with an additional 21 (8%) partially completed, and represents a failure to achieve the expected level of completion. Patients reported experiencing up to 51 and a median of 30 symptoms across all time points, highlighting the complexity of symptom assessment in acute cancer care. While weekly implementation of the PRO-CTCAE may not be feasible outside of clinical trial settings, this study highlights the breadth of symptoms experienced.

Implementing an educational resource for patients participating in cancer clinical trials during the pandemic.

This research is centred in the specialty of early phase cancer research - the branch of clinical research that focuses on phase one and phase two clinical trials. The aim was to gain an understanding of the complexity of work involved in implementing an educational intervention within the clinical pathway for newly referred early phase cancer clinical trial patients. The May and Finch Normalisation Process Theory (NPT) was used to understand, develop and evaluate the process of embedding an educational resource at referral hospital sites. Elements emerged from the evaluation that provide insights into the complexity of the implementation work that took place. The main elements were: pandemic-related challenges, change management, leadership, shared purpose, teamwork, workforce capacity and patient outcomes. The findings shed light on the barriers to or facilitators of the implementation of the educational resource.

The Polyamine Analogue Ivospemin Increases Chemotherapeutic Efficacy in Murine Ovarian Cancer.

Polyamines are small polycationic alkylamines that are absolutely required for the continual growth and proliferation of cancer cells. The polyamine analogue ivospemin, also known as SBP-101, has shown efficacy in slowing pancreatic and ovarian tumor progression in vitro and in vivo and has demonstrated encouraging results in early pancreatic cancer clinical trials. We sought to determine if ivospemin was a viable treatment option for the under-served platinum-resistant ovarian cancer patient population by testing its efficacy in combination with commonly used chemotherapeutics. We treated four ovarian adenocarcinoma cell lines in vitro and found that each was sensitive to ivospemin regardless of cisplatin sensitivity. Next, we treated patients with ivospemin in combination with four commonly used chemotherapeutics and found that ivospemin increased the toxicity of each; however, only gemcitabine and topotecan combination treatments were more effective than ivospemin alone. Using the VDID8+ murine ovarian cancer model, we found that the addition of ivospemin to either topotecan or gemcitabine increased median survival over untreated animals alone, delayed tumor progression, and decreased the overall tumor burden. Our results indicate that the combination of ivospemin and chemotherapy is a worthwhile treatment option to further explore clinically in ovarian cancer.

Decline in Smartphone-Assessed Physical Activity Level is Associated With Clinical Outcomes in Phase I/II Clinical Cancer Trials.

A decline in physical function may be an early predictor for complications of cancer treatment. This study examined whether repeated objective smartphone measurements of physical activity and exercise capacity in patients with cancer are feasible during early-phase clinical trials (EPCTs) and whether a decline in physical function is associated with clinical outcomes. Physical activity (steps/day) and exercise capacity (6-minute walk test [6MWT]) were measured with a smartphone before EPCT start (T0) and after 4 weeks (T1) and 8 weeks (T2). Univariable logistic regression analyzed associations between a decline in step count (≥20%), 6MWT distance (≥10%), or deterioration of ECOG performance status (PS) and trial discontinuation at 8 weeks and 90 days. Cox proportional hazards models were used to examine associations with progression-free survival (PFS) and overall survival (OS), adjusting for trial phase (I vs II), cancer type (hematologic malignancy vs solid tumor), and PS (0 vs ≥1). Among 117 included patients, valid step count and 6MWT measurements were available for 96.6% and 76.7% of patients at T0, 74.4% and 53.3% at T1, and 89.7% and 54.4% at T2, respectively. Patients experiencing step count decline between T0 and T1 had higher odds of trial discontinuation at 8 weeks (odds ratio, 8.67; 95% CI, 1.94-61.43), and decline between T1 and T2 was associated with discontinuation at 90 days (odds ratio, 5.20; 95% CI, 1.43-21.14). Step count decline was significantly associated with shorter PFS (hazard ratio, 3.54; 95% CI, 2.06-6.08) and OS (hazard ratio, 2.31; 95% CI, 1.26-4.23). Declines in 6MWT distance or deterioration in ECOG PS were not associated with trial discontinuation or survival. Repeated smartphone measurements of physical activity are feasible in patients participating in EPCTs. Additionally, physical activity decline is significantly associated with trial discontinuation, PFS, and OS. Hence, we envision that objective smartphone measurements of physical activity will contribute to optimal treatment development for patients with cancer.

The mitochondrial protease ClpP is a druggable target that controls VSMC phenotype by a SIRT1-dependent mechanism

Vascular smooth muscle cells (VSMCs), known for their remarkable lifelong phenotypic plasticity, play a pivotal role in vascular pathologies through their ability to transition between different phenotypes. Our group discovered that the deficiency of the mitochondrial protein Poldip2 induces VSMC differentiation both in vivo and in vitro. Further comprehensive biochemical investigations revealed Poldip2's specific interaction with the mitochondrial ATPase caseinolytic protease chaperone subunit X (CLPX), which is the regulatory subunit for the caseinolytic protease proteolytic subunit (ClpP) that forms part of the ClpXP complex – a proteasome-like protease evolutionarily conserved from bacteria to humans. This interaction limits the protease's activity, and reduced Poldip2 levels lead to ClpXP complex activation. This finding prompted the hypothesis that ClpXP complex activity within the mitochondria may regulate the VSMC phenotype.Employing gain-of-function and loss-of-function strategies, we demonstrated that ClpXP activity significantly influences the VSMC phenotype. Notably, both genetic and pharmacological activation of ClpXP inhibits VSMC plasticity and fosters a quiescent, differentiated, and anti-inflammatory VSMC phenotype. The pharmacological activation of ClpP using TIC10, currently in phase III clinical trials for cancer, successfully replicates this phenotype both in vitro and in vivo and markedly reduces aneurysm development in a mouse model of elastase-induced aortic aneurysms. Our mechanistic exploration indicates that ClpP activation regulates the VSMC phenotype by modifying the cellular NAD+/NADH ratio and activating Sirtuin 1. Our findings reveal the crucial role of mitochondrial proteostasis in the regulation of the VSMC phenotype and propose the ClpP protease as a novel, actionable target for manipulating the VSMC phenotype.

Study Participants, Future Patients, and Outcomes That Matter in Cancer Clinical Trials

Study Participants, Future Patients, and Outcomes That Matter in Cancer Clinical Trials

Anticancer Mechanism of Astragalus Polysaccharide and Its Application in Cancer Immunotherapy.

Astragalus polysaccharide (APS) derived from A. membranaceus plays a crucial role in traditional Chinese medicine. These polysaccharides have shown antitumor effects and are considered safe. Thus, they have become increasingly important in cancer immunotherapy. APS can limit the spread of cancer by influencing immune cells, promoting cell death, triggering cancer cell autophagy, and impacting the tumor microenvironment. When used in combination with other therapies, APS can enhance treatment outcomes and reduce toxicity and side effects. APS combined with immune checkpoint inhibitors, relay cellular immunotherapy, and cancer vaccines have broadened the application of cancer immunotherapy and enhanced treatment effectiveness. By summarizing the research on APS in cancer immunotherapy over the past two decades, this review elaborates on the anticancer mechanism of APS and its use in cancer immunotherapy and clinical trials. Considering the multiple roles of APS, this review emphasizes the importance of using APS as an adjunct to cancer immunotherapy and compares other polysaccharides with APS. This discussion provides insights into the specific mechanism of action of APS, reveals the molecular targets of APS for developing effective clinical strategies, and highlights the wide application of APS in clinical cancer therapy in the future.

Enhancing Understanding and Engagement: Investigating the Impact of Education on Cancer Clinical Trial Participation

Enhancing Understanding and Engagement: Investigating the Impact of Education on Cancer Clinical Trial Participation

Social Determinants of Health and the Availability of Cancer Clinical Trials in the United States

This cohort study investigates whether county-level social determinants of health are associated with cancer clinical trial availability in the United States.

Management of patients with diffuse intrinsic pontine glioma in Australia and New Zealand: Australian and New Zealand Children's Haematology/Oncology Group position statement.

The main mission of the Australian and New Zealand Children's Haematology and Oncology Group (ANZCHOG) is to develop and facilitate local access to the world's leading evidence-based clinical trials for all paediatric cancers, including brain tumours, as soon as practically possible. Diffuse intrinsic pontine gliomas (DIPGs) - a subset of a larger group of tumours now termed diffuse midline glioma, H3K27-altered (DMG) - are paediatric brain cancers with less than 10% survival at two years. In the absence of any proven curative therapies, significant recent advancements have been made in pre-clinical and clinical research, leading many to seek integration of novel therapies early into standard practice. Despite these innovative therapeutic approaches, DIPG remains an incurable disease for which novel surgical, imaging, diagnostic, radiation and systemic therapy approaches are needed. All patients with DIPG should be discussed in multidisciplinary neuro-oncology meetings (including pathologists, neuroradiologists, radiation oncologists, neurosurgeons, medical oncologists) at diagnosis and at relapse or progression. Radiation therapy to the involved field remains the local and international standard of care treatment. Proton therapy does not yield a superior survival outcome compared with photon therapy and patients should undergo radiation therapy with the available modality (photon or proton) at their treatment centre. Patients may receive concurrent chemotherapy or radiation-sensitising agents as part of a clinical trial. Biopsy should be offered to facilitate consideration of experimental therapies and eligibility for clinical trial participation. After radiation therapy, each patient should be managed individually with either observation or considered for enrolment on a clinical trial, if eligible, after full discussion with the family. Re-irradiation can be considered for progressive disease. Every child diagnosed with DIPG should be offered enrolment on a clinical trial where available. Access to investigational drugs without biological rationale outside the clinical trial setting is not supported. In case of potentially actionable target identification with molecular profiling and absence of a suitable clinical trial, rational targeted therapies can be considered through compassionate access programs.

Abstract PO3-27-08: Geographic Distribution and Accessibility of Clinical Trials for Advanced-Stage Breast Cancer in the United States: A Focus on Rural and Minority Health Disparities

Abstract Background: Our research examines the geographical distribution and accessibility of clinical trials for metastatic breast cancer patients in the U.S., spotlighting the challenges faced by rural communities and minority groups. Prior research indicated nearly half of these patients would have to commute over an hour to reach a trial site. [1] Our study provides a refreshed perspective on this issue, offering a more comprehensive analysis. Methods: Utilizing the ClinicalTrials.gov portal, we identified active interventional clinical trials for metastatic breast cancer patients as of November 25, 2022. We obtained distinct zip codes linked to these trials and, using 2020 census data, estimated the proportion of the U.S. populace residing within specific distances from these sites. Our analysis encompassed ethnicity, and other socio-economic parameters. Using GIS software, we also developed illustrative maps to visually represent the U.S. clinical trial accessibility landscape. Results: The majority of Americans diagnosed with metastatic breast cancer have clinical trials within their reach. A significant 81.8% of the U.S. populace resides within a 30-mile radius of a relevant clinical trial site. However, there is significant variation among ethnic groups, especially among American Indians, where 56.5% live within 30 miles of a clinical trial site. Conclusions: While a commendable 81.8% of the U.S. population resides within 30 miles of a metastatic breast cancer clinical trial site, our data underscores the uneven geographical spread of these trials. Our findings underscore the need for strategic initiatives to ensure clinical trials are within reach for every individual, irrespective of their location or background. Reference: 1. Galsky MD, Stensland KD, McBride RB, Latif A, Moshier E, Oh WK, Wisnivesky J. Geographic accessibility to clinical trials for advanced cancer in the United States. JAMA Intern Med. 2015 Feb;175(2):293-5. PMID: 25437434. Map of 30-, 60-, and 120-mile buffers from clinical trial sites open to patients with metastatic breast cancer. The U.S. Population living withing 30-, 60-, and 120-miles of an open clinical trial site for patients with metastatic breast cancer. Citation Format: Emily Westergard, Abigail Swenson, Zachary Schroeder, Wade Swenson. Geographic Distribution and Accessibility of Clinical Trials for Advanced-Stage Breast Cancer in the United States: A Focus on Rural and Minority Health Disparities [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 PO3-27-08.

Abstract PO3-09-10: Minority participation in breast cancer therapeutic trials at an NCI-CCC affiliated safety-net system: Advancing equity in clinical research

Abstract Authors: Nasir Qureshi, MBBS Fabian Robles, MS Mai Badran, MBBS Nisha Unni, MD Hsiao C Li, MD Samira Syed, MD Glenda Delgado-Ramos, MD Sangeetha Reddy, MD Heather McArthur, MD Navid Sadeghi, MD Title: Minority participation in breast cancer therapeutic trials at an NCI-CCC affiliated safety-net system: Advancing equity in clinical research. Introduction: Participation of under-represented minorities (URMs) in clinical trials enhances the generalizability of the findings and can also improve clinical outcomes. Multiple factors, such as access, language barrier, distrust, and misconceptions, negatively impact URM enrollments in cancer clinical trials. Here we describe our approach to increase participation of breast cancer URMs in therapeutic trials at an academic-affiliated safety-net system. Methods: Parkland Health (PH) is a large safety-net system in Dallas County, Texas, and is affiliated with the NCI-CCC designated Harold C. Simmons Comprehensive Cancer Center (SCCC) at UT Southwestern. A dedicated team of SCCC research coordinators support the clinical trial operations at PH. In 2020, several steps were taken to increase access and enrollment of URMs in breast cancer trials at PH including review and optimization of the trial portfolio (more trials in curative intent setting), proactive screening, increasing provider awareness, and addition of a bilingual (English/Spanish) patient navigator to the research team. Data for 2018-2019 (pre-intervention) and 2021-2022 (post-intervention) is presented here. Data for 2020 is excluded due to the impact of COVID-19 pandemic on trial operations. Results: Racial and ethnic minorities composed the majority of breast cancer patients at PH (52% Hispanics, 32% Blacks). Ten percent of new patients at PH presented with metastatic disease. In 2018-2019, PH's portfolio included 13 therapeutic trials, 5 of which (38%) were in metastatic setting and 3 required a biomarker. A total of 47 breast cancer patients were enrolled in 11 therapeutic trials at PH, accounting for an average annual accrual rate of 6.1% (7.6% in 2018 and 4.5% in 2019). Accrual to trials in the metastatic setting accounted for 11% (5/47) of enrollments. Two trials in the metastatic setting had zero accruals. In 2021-2022, 16 trials were open at PH, including 7 cooperative group, 4 industry-sponsored (ISTs), and 5 Investigator-Initiated trials (IITs). Five trials (31%) were in metastatic setting and 4 required a genomic biomarker. A total of 87 patients were enrolled in 2021-22, representing an 85% increase in the accruals over the baseline (2018-2019). The annual accrual rates for 2021 and 2022 were 10.5% (43/409) and 10.4% (44/423), respectively. In 2021-22, 63 were enrolled in cooperative group studies, 20 in IITs, and 4 in ISTs. Accrual to trials in the metastatic setting accounted for 6% (5/87) of enrollments. Two studies had zero accruals. The majority of the trial participants (77/87; 89%) belonged to URMs (64 Hispanic, 13 Black). Overall participation rate was 67% (87/129) and was significantly higher in Hispanics compared to Blacks (77% vs 41% - p < 0.001). Among Black patients who declined participation, 42% (8/19) cited lack of interest as the reason, which may reflect distrust or misperceptions regarding clinical trials. Conclusions: The collaboration between academic centers and safety-net systems provides a unique opportunity to promote equity in clinical trials by increasing access and enrollment of URMs. Developing a balanced portfolio that matches the patient population, enhanced screening, and incorporating clinical trial patient navigation at our institution resulted in a sustained increase in the number of URM trial participants. Given the lower participation rate among eligible Black patients, we aim to expand our clinical trial navigation program to better address the distrust and misperceptions regarding clinical trials, as a strategy to further improve trial participation at our institution. Citation Format: Nasir Qureshi, Fabian Robles. Minority participation in breast cancer therapeutic trials at an NCI-CCC affiliated safety-net system: Advancing equity in clinical research [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 PO3-09-10.

Abstract PO1-10-12: Advancing Gender Equity: A Closer Look at Women's Representation in Leading Breast Cancer Clinical Trials

Abstract Introduction: Clinical trials serve as pivotal sources for evidence-based medicine, wielding substantial influence within the medical and scientific community. In recent years, heightened attention has been directed towards encouraging greater female involvement and advancing their representation across various domains of the medical field. Female oncologists tend to focus more over breast cancer as a subspeciality and focused practice. Consequently, this observational study seeks to assess the present status of gender equity in leading breast cancer clinical trials, with the aim of identifying potential concerns and mitigating future risks of bias. By delving into this analysis, we can shed light on the current landscape and pave the way for improved inclusivity and fairness in breast cancer research. Methodology: To examine the portrayal of female principal investigators (PIs) in breast cancer clinical trials over the past two decades, we conducted a thorough search of breast cancer clinical trials listed on ClinicalTrials.gov. Furthermore, we employed https://gender-api.com to assess the gender of each PI and calculate the experience in the medical field of the PI by subtracting the PI graduation year from the year of conducting the clinical trial. In addition, we gathered pertinent details concerning the PIs and the clinical trials, and subsequently subjected the data to univariate analyses to detect any noteworthy distinctions between male and female PIs. Results: Over the span of the past twenty years, a total of 9,145 cancer clinical trials were conducted, with 1,127 (12.32%) focusing specifically on breast cancer. Through our rigorous efforts, we managed to gather comprehensive information about the principal investigators (PIs) in 788 (69.92%) of these clinical trials. Notably, we discovered that 419 (53.17%) of these trials were led by female investigators. Upon scrutinizing the characteristics of the PIs, we observed several significant distinctions between male and female PIs. Female PIs exhibited a lower median age (57.0 vs. 60.0) and possessed less medical experience (17 vs. 22 years) compared to their male counterparts (P< 0.001). Furthermore, we found a substantial divergence in the funding sources for the clinical trials between the genders. Female-led trials received a lower percentage of industrial funding (13.1% vs. 24.2% for males, P< 0.001) but showcased a significantly higher percentage of university funding (38.7% vs. 28.0% for males, P< 0.001). Most of the clinical trials led by female PIs were categorized as phase 2 trials (82.8% vs. 66.8% for males) and were conducted in single centers (61.2% vs. 52.6% for males), demonstrating a noteworthy statistical difference (P< 0.001) in both cases. However, no statistically significant disparities were found between male and female PIs in terms of termination rates, publication rates, or the type of intervention utilized in the clinical trials. Furthermore, the ratio of females PI wasn’t different throughout the time as the liner regression model estimated effect was -0.009 with P= 0.065. Conclusions: The study shows the great effort done by female researchers, even though they have lower age, experience, and support from the industrial companies and lower opportunity to have bigger multicenter clinical trials, they still manage to have equivalent rate of termination and publication of the clinical trials showing their capability to lead clinical trials and the need to be supported to maintain the gender equity in leading the breast cancer clinical trials. However, female involvement in other cancer sites might be different and needs to be looked at. Citation Format: Abdulrahman Alhajahjeh, Ghayda’ Bader, Basil Abdin, Taima’ Bader, Saji Aweidah, Layla El-Amayreh, Hikmat Abdel-Razeq. Advancing Gender Equity: A Closer Look at Women's Representation in Leading Breast Cancer Clinical Trials [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 PO1-10-12.

Abstract PO5-20-05: The FOR ME (Fostering Opportunities in Research through Messaging and Education) study: Using multiple qualitative methods to develop a culturally sensitive narrative intervention to promote equity in clinical trials

Abstract Background: Black women are more likely to present with advanced stage disease and to die following a breast cancer (BC) diagnosis compared to women from other racial/ethnic groups. In 2020, only 7.2% of enrollees in clinical trials that led to the approval of 3 novel drugs for breast cancer were Black. While there are many contributing factors to this inequity (i.e., tumor biology, social and structural health determinants, racial injustice, and differential access to and utilization of high-quality mammography, diagnostics, and therapies), persistent underrepresentation of Black patients in cancer clinical trials (CTs) slows scientific advancements. Objective: The aim of this study is to develop, optimize, and test a narrative decision aid intervention (web-based video) for Black women diagnosed with BC to promote shared decision making and CT participation. The first aim is to conduct multiple qualitative methods with multi-level stakeholders to identify barriers, facilitators, and intervention priorities that would assist Black breast cancer patients to make informed decisions about participating in clinical trials. The second aim is to create a culturally sensitive, narrative intervention designed to support decision making and motivate Black breast cancer patients to participate in clinical trials. Aim 3 will then pilot a study to determine acceptability of the intervention among patients and assess whether it increases clinical trial participation in a safety net oncology practice. Methods: Guided by community-based participatory research approaches, we used multiple qualitative methods (key informant interviews (KIIs) and story circles) to identify barriers and facilitators that support decision-making and CT participation. The KIIs, completed in-person, via phone, or video conferencing, were recorded and professionally transcribed. The research team used thematic analysis and inductive coding approaches. Next, interviews and focus groups will invite feedback on the educational/motivational content of the intervention and will be used to develop a culturally sensitive script and story boards. A video production company will produce the narrative intervention. Finally, focus groups and interviews with participant cohorts will provide feedback on the completed intervention. Black women diagnosed with BC will view the intervention in an oncology clinic. Using a pretest/posttest design, we will analyze the acceptability of the intervention and its effect on intention to participate in clinical trials. We will then conduct a quasi-experimental study in a safety net oncology practice to determine whether the rate of clinical trial participation among Black breast cancer patients increases following implementation of the intervention as a standard component of new patient education. Progress: Recruitment started in July 2022 and currently 30 of 30 interviews with patients are completed, 20 of 20 interviews with clinical stakeholders (oncologists and clinical trial staff) are completed, and 14 of 20 interviews with advocates and community partners are completed. Data collection and the analysis of the interviews and story circles is ongoing. Citation Format: Neha Hippalgaonkar, Ryan Nguyen, Leslie Carnahan, Vida Henderson, Tigist Mersha, Eliza Cohn, Kauthar Salum, Ana Williams, Lolita Coleman, Beulah Brent, AnneMarie Murphy, Paris Thomas, Paramjeet Khosla, Kent Hoskins. The FOR ME (Fostering Opportunities in Research through Messaging and Education) study: Using multiple qualitative methods to develop a culturally sensitive narrative intervention to promote equity in clinical trials [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 PO5-20-05.

Abstract PO2-03-02: Technology-enabled identification of low-risk breast cancer survivors for personalized survivorship care

Abstract Background. Advancements in cancer medicine have resulted in prolonged survival for the majority of patients. Personalized care pathways which account for clinical needs of this growing population of cancer survivors—and which address oncology workforce shortages—are urgently needed. Rapid identification of low-risk cancer survivors who could be cared for in other settings is a critical element of personalized care. Here we present final algorithm performance on risk-stratification from an ongoing clinical trial evaluating a primary care physician-led cancer survivorship clinic for breast cancer survivors. We captured data on real-time clinical risk stratification of early-stage patients between 6-36 months post-treatment. Methods. With oncology stakeholder input, we developed a screening algorithm to identify low-risk breast cancer survivors from the electronic medical record based on data from pathology, treatment, and utilization records. The algorithm identified patients meeting study eligibility: adult stage 0-IIb breast cancer patients diagnosed with first primary cancer, excluding those with treatments indicative of high-risk or metastatic disease, ongoing ovarian suppression, neoadjuvant therapy, or enrollment in other cancer clinical trials. Next, the treating oncologist was asked to confirm or deny patient eligibility; if denied, we tracked and categorized the reason provided for ineligibility. We describe: 1) characteristics and proportions of patients identified by the algorithm; 2) a breakdown of patients confirmed or denied eligibility; and 3) oncologists’ reasons for ineligibility. Results. The algorithm identified 1186 patients. Of those, 91 were flagged by oncology as not followed (e.g., consult only), and 204 were not categorized. Of the remaining 890 patients, 716 (81%) were categorized as eligible. Mean age was 62 years (SD: 11.4, Table 1). There were significant differences by stage, with a higher proportion of stage 0 in the eligible group (24% vs. 18%) and a lower proportion of stage II (24% vs. 35%). There was also a significant difference by HER2 status, with a greater proportion of HER2+ patients categorized as eligible (21% vs. 16%). There were significant differences by race/ethnicity, with a higher proportion of Asian and Black patients categorized eligible (14% vs. 8%, and 28% vs. 17%, respectively) and fewer Hispanic and White patients categorized eligible (26% vs. 36%, and 30% vs. 37%, respectively). There were not significant differences by ER/PR, surgery, or endocrine therapy. Reasons for ineligibility included: suspicious for recurrence (6%), new primary disease (3%), considered high-risk based on genetic/tumor factors (9%), co-occurring heme/oncology disorder (9%), treatment-related concerns (e.g., patient declined chemotherapy) (7%), complex case/condition (11%), patient preference per conversation with oncologist (32%), other (19%), and lost to follow-up (4%). Conclusions. Leveraging technology to support survivorship in the primary care setting is critical. Our findings demonstrate that consensus-based risk algorithms with oncologist review can effectively perform identification of low-risk patients who may be appropriately transitioned to other settings for survivorship care. These patients may benefit from primary care-led survivorship with a focus on healthy lifestyle, managing comorbid conditions, and psychosocial care. Eligible/Ineligible per oncologist by patient demographics and cancer characteristics Citation Format: Farah Brasfield, Aiyu Chen, Eric Haupt, Lindsay Lyons, Talar Habeshian, Corrine Munoz-Plaza, Ernest Shen, Huong Nguyen, Michael Gould, Alexander Ferreira, Allen Joo, Seyed Monemian, Christy Lai, Yung-Mee Park, Hollis Lee, Steven Steinberg, Patricia Ganz, Erin Hahn. Technology-enabled identification of low-risk breast cancer survivors for personalized survivorship care [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 PO2-03-02.

Abstract PO1-03-07: Revisiting the potential of pathological complete response as a surrogate for long-term survival outcomes in triple-negative breast cancer at the trial-level

Abstract Background: Pathological complete response (pCR) has been used as a primary endpoint in neoadjuvant clinical trials for non-metastatic breast cancer and as a surrogate endpoint for long-term survival outcomes. The U.S. Food and Drug Administration (FDA) accepted pCR as a surrogate endpoint for the approval of new drugs in the neoadjuvant setting in high-risk early-stage breast cancer. However, though the Collaborative Trials in Neoadjuvant Breast Cancer (CTNeoBC) pooled analysis in 2014 showed that at the patient level achieving pCR was associated with longer overall survival (OS) and event-free survival (EFS), at the trial-level the association between high pCR rate and better OS and EFS outcomes was weak (coefficient of difference [R2]; 0.03 and 0.24, respectively) among all subtypes of breast cancer. A recent study reported that this association at the trial-level was similarly weak among Human Epidermal Growth Factor Receptor-2 (HER-2) positive breast cancer (R2; 0.02 and 0.23, respectively). However, the potential surrogacy of pCR rate for OS and EFS in triple-negative breast cancer (TNBC) in the neoadjuvant setting has not been well studied in a comprehensive manner. Moreover, because of significant advances in systemic treatment strategies in TNBC over the past decade including a combination of immune checkpoint inhibitors (ICIs) with conventional cytotoxic agents, the trial-level surrogacy needs to be reassessed in recently published neoadjuvant clinical trials for TNBC. Our primary objective is to assess the association between pCR rate and survival outcomes in neoadjuvant clinical trials for TNBC by collecting data from articles published after the CTNeoBC article in 2014. Methods: We performed a systematic literature search based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed, Cochrane Library, and Web of Science databases. Articles published between January 1, 2014, and March 31, 2023, were searched. We included only randomized control trials of neoadjuvant treatments for clinical stage I-III TNBC that compared two or more regimens followed by curative intent breast surgery. The selected trials had data for odds ratio (OR) for pCR and hazard ratios (HRs) either for OS or for EFS or disease-free survival (DFS). We excluded trials including estrogen receptor positive, progesterone receptor-positive, or HER-2 positive diseases, and those without data enough to obtain ORs for pCR, HRs for OS, EFS, or DFS. Unpublished data as a full article was also excluded. If EFS could not be obtained from the articles, DFS was used in place of EFS. Two independent investigators (TY and TF) searched and extracted data. Any disagreement was resolved by discussion with the third author (ZZ). A linear regression model on a logarithmic scale weighted by the sample size of each trial was performed and the R2 was used to assess the trial-level association between OR for pCR and HRs for OS or EFS. Results: We identified eight trials with a total of 2,926 patients. Three of the eight trials used ICIs in the intervention arm. One trial did not provide OS data and was not included in the OS analysis. In four trials, EFS was not available and DFS was used for EFS analysis. The R2 was 0.191 (95% confidence interval [CI], 0.165 to 0.218) for OS and 0.193 (95% CI, 0.167 to 0.219) for EFS. Conclusions: Similarly to the previous reports, our findings suggest that the surrogacy of the pCR rate for OS and EFS in recent neoadjuvant clinical trials for TNBC is weak. At this moment, there is no strong evidence to support using pCR as a surrogate for long-term survival outcomes in neoadjuvant clinical trials for TNBC. Citation Format: Toru Yoshino, Zao Zhang, Ryota Sato, Stanley Lipkowitz, Takeo Fujii. Revisiting the potential of pathological complete response as a surrogate for long-term survival outcomes in triple-negative breast cancer at the trial-level [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 PO1-03-07.

Abstract PO5-17-04: Tolerability of pertuzumab in older adults with HER2 positive breast cancer: A single institution experience

Abstract Background: Tumor HER2 over-expression occurs in 10 to 15% of older adults with breast cancer (BC). Combination HER2-directed therapy (pertuzumab and trastuzumab) with chemotherapy (CT) is the standard treatment for early and advanced HER2-positive bc. However, a study of more than 1,300 Medicare beneficiaries showed that about half of patients (pts) aged 65 or older with stage I to III HER2 positive bc did not receive trastuzumab-based therapy. This is likely due to concern for tolerability as older women remain underrepresented in clinical trials of breast cancer making it difficult to extrapolate tolerability of these agents in these patients. In the Neosphere and TRYPHAENA studies, the mean age of pts were 49.8 and 50.6 years, respectively. We examined the real-world tolerability of pertuzumab in combination with trastuzumab and systemic ct in women over the age of 65 with HER2 positive bc. Methods: An IRB approved retrospective review of medical records was conducted evaluating pts over the age of 65 with early or advanced HER2 positive bc treated at The Ohio State University Comprehensive Cancer center from January 1, 2015 to May,1 2020. Descriptive statistics (means, standard deviations, medians and ranges for continuous variables and frequencies and percents for categorical variables) were used to summarize disease and patient characteristics for pts enrolled in this study and treated with pertuzumab. The total number of planned and completed cycles of treatment as well as the number of treatment delays and dose reductions were also summarized using frequencies and percentages. The same descriptive statistics were used to summarize the number of grade II or IV toxicities and pathologic complete response (pCR) in the neoadjuvant setting. Results: A total of 71 pts met inclusion criteria. Mean age was 76 years (SD 4.1). Of these pts, 62 had stage I-III disease and 9 had metastatic disease. Additionally, 68% (48/71) had estrogen positive (ER) disease whereas 32% (23/71) had ER negative disease. Neoadjuvant systemic therapy was provided to 81% (50/62) of non-metastatic pts and 19% (12/62) received adjuvant therapy. The median number of completed neoadjuvant cycles (ct plus trastuzumab and pertuzumab) was 5.4 (SD 1.5). Among those who received pertuzumab with systemic ct in the neoadjuvant setting, 46% (23/50) of pts achieved a pCR (56% for ER negative disease and 41% for ER positive disease) The median number of completed adjuvant cycles (ct plus trastuzumab and pertuzumab) was 4.9 (SD 2.0). Pts with stage I to III disease completed a mean of 8.6 (SD 5.0) targeted therapy cycles (pertuzumab/trastuzumab). Pts with metastatic disease had a median of 5.7 (SD 1.0) cycles of ct plus trastuzumab and pertuzumab and received a mean of 34.4 (SD 36.0) cycles of maintenance pertuzumab. Treatment delay by 7 or more days occurred in 11% (8/71) of pts whereas 25% (18/71) of pts discontinued pertuzumab early. Pertuzumab termination occurred due to toxicity in 44% (8/18), metastasis in 11% (2/18), and other causes in 44% (8/18) of cases. For toxicities, 2% (1/51) of patients reported grade 3 pain, 25% (2/8) reported grade 3 fatigue, and 12% reported grade 4 diarrhea (1/8) (Table 1). Conclusions: Our study showed that pertuzumab was well tolerated in older pts with bc in the real-world setting. However, 25 % of pts still discontinued pertuzumab early which illustrates the importance of identifying pts who are at higher risk for toxicities prior to starting treatment. Table 1 Reported adverse events in patients age 65 and older receiving pertuzumab Citation Format: Nicole Williams, Austin Warmbier, Dureti Doto, Marilly Palettas, Julie Stephens, Dionisia Quiroga, Kai Johnson, Ashley Pariser, Mathew Cherian, Sagar Sardesai, Daniel Stover, Margaret Gatti-Mays, Robert Wesolowski, Bhuvana Ramaswamy. Tolerability of pertuzumab in older adults with HER2 positive breast cancer: A single institution experience [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 PO5-17-04.

Abstract PO1-03-03: STEEP criteria v2.0 validation: A multi-trial analysis using GEICAM and TRIO adjuvant trials to evaluate surrogate endpoints for overall survival

Abstract Background: Standardized definitions of efficacy endpoints are needed to improve clinical trial designs, data reporting and interpretation of results, and to allow cross-trial comparisons. STEEP (Standardized Definitions for Efficacy Endpoints) criteria were proposed in 2007 by an expert panel from the National Cancer Institute (NCI) to provide common definitions for clinical trials in early breast cancer (BC). Invasive disease-free survival (IDFS) was selected as a candidate surrogate endpoint for overall survival (OS) in adjuvant trials and has been widely used in the last 15 years. Advances in BC systemic treatment led to review these criteria (STEEP v2.0), with the definition of a new modified endpoint: invasive BC-free survival (IBCFS). IBCFS excludes second primary non-breast invasive cancers from IDFS which may better detect efficacy effects when the toxicity profile of the intervention is well-known and the risk of second primary cancer is small. Methods: We proposed a multi-trial analysis of 8 adjuvant chemotherapy (CT) trials from GEICAM and TRIO to evaluate the different surrogate endpoints defined in the STEEP v2.0. Trial-level surrogacy was assessed through correlation between the ln hazard ratio (HR) of OS and the ln HR of the different studied endpoints across trials. The correlation was estimated by the weighted, by trial size, least squares regression (WLS) line and evaluated comparing the R2 values between OS and the corresponding endpoint tested. Primary analyses evaluated the correlation of OS with IDFS/IBCFS. Secondary analyses evaluated the correlation of OS with other STEEP v2.0 endpoints (distant disease-free survival [DDFS], distant relapse-free survival [DRFS], recurrence-free survival [RFS], recurrence-free interval [RFI] and distant recurrence-free interval [DRFI]) and explored the surrogacy between OS and all endpoints in specific groups of patients (pts) according to their risk of relapse: hormone receptors positive (HR+)/HER2-negative (HER2-) pts with intermediate/high and high-risk and triple negative (TN) pts. Results: A total of 14,473 pts were included. Median age was 50 years (range, 20–82). All were female, and 51.8% were postmenopausal. With a median follow-up of 115 months (range, 0.0–188) we found 2,504 OS events, 4,146 IDFS events (60.9% being distant recurrences) and 3,810 IBCFS events (62.4% being distant recurrences). For each trial, HR of OS, IDFS and IBCFS indicated same conclusions. If HR< 1 for OS, it was also for IDFS and IBCFS and the same was true when HR >1. R2 results of the weighted linear correlations between the ln HR of OS versus (vs) IDFS and OS vs IBCFS were 0.86 and 0.89, respectively. Confidence intervals (CI) at 95% were both overlapping. All other efficacy endpoints showed strong correlation with OS in the overall analysis. R2 values for HR+/HER2- intermediate/high and high-risk pts were 0.89 (OS vs IDFS) and 0.84 (OS vs IBCFS). For TN pts the correlations were weaker, being 0.63 (OS vs IDFS) and 0.73 (OS vs IBCFS). All WLS R2 values are described in the table. Conclusions: All tested STEEP v2.0 endpoints were strongly correlated with OS (R2 close to 1), meaning that their use as surrogate endpoints for adjuvant CT trials is appropriate. Notably, no differences were found between them in this multi-trial analysis. Therefore, none of them is more appropriate than other to discriminate the value of a new intervention vs comparator in adjuvant CT studies with mature data and long-term follow-up. Table: Citation Format: Sara López-Tarruella, Marina Pollan, Ander Urriticoechea, Eva Carrasco, Gonzalo Spera, Miguel Martín, Begoña Bermejo, Linnea Chap, Manuel Ruíz - Borrego, John Crown, Jose Angel García-Sáenz, Arlene Chan, Angel Guerrero, Valerie Bee, Lourdes Calvo, Rodrigo Fresco, Andrea Blasco, Andrés Hernando, Dennis Slamon. STEEP criteria v2.0 validation: A multi-trial analysis using GEICAM and TRIO adjuvant trials to evaluate surrogate endpoints for overall survival [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 PO1-03-03.

Abstract PO4-18-05: Safety and Feasibility of Administration of an Oral Cannabis Preparation in The Preoperative Period in Breast and Oral Cavity Cancer

Abstract Introduction- Cannabis is world’s oldest cultivated medicinal plant. It has potential applications in oncology, in reducing chronic pain, stimulating appetite, alleviating nausea/vomiting, improving overall well-being as well as its anti-cancer properties. We conducted a phase-1 dose escalation study to determine safety of pre-operative oral cannabis in breast and oral cavity squamous cell carcinoma (OC-SCC) with an intent to explore its anticancer potential in the “pre-operative” window. The primary objective was to determine maximum tolerated dose (MTD) and establish dose limiting toxicity (DLT). Secondary objectives were pharmacokinetic profiling and transcriptomic analysis of tumour tissue. Methodology- Primary objective was to determine maximum tolerated dose (MTD) and establish dose limiting toxicity (DLT). Secondary objectives were pharmacokinetic profiling and transcriptomic analysis of tumour tissue. Non-metastatic breast and OC-SCC patients planned for curative surgery were consented after thorough medical and mini-psychiatric evaluation with Brief Psychiatry Rating Scale (BPRS). The investigational product (IP) comprised of a capsule containing 2.5mg of tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD) in 100 mg monocrotolyn oil extract of dried leaves of C. sativa. The capsules were manufactured in an Ayurvedic GMP facility. The classical 3+3, phase-1 design used modified Fibonacci sequence for dose escalation, starting with 5mg THC+5mg CBD. Patients received IP once a day for 5 days after breakfast with hemodynamic and psychiatric monitoring and underwent the planned surgery on day-6. Pharmacokinetic samples were collected at predefined time-points and plasma levels of THC, 11-OH-THC, 11-COOH-THC and CBD were determined using a validated LC-MS/MS method. Tumour tissue was collected before 1st dose of cannabis and during surgery for biomarker analysis. Results- A total of 12 patients were enrolled (6-breast, 3-buccal mucosa, and 3-tongue cancers). First 3 patients completed the study without DLT at 5+5mg dose. A DLT was observed at dose level-2 (10+10mg) and therefore additional 3 patients were enrolled at the same dose. Two patients out of six at this dose had DLT (anxiety- grade-3 and somnolence- grade-2) necessitating dose de-escalation in the next cohort. At 7.5+7.5mg dose, all 3 patients tolerated the IP(MTD). Ten patients completed the study protocol. Common adverse effects were headache (2/12, grade-1), heavy head (8/12, grade-1), hypotension (2/12, grade-1 and 3), epigastric discomfort (1/12, grade-1), diarrhoea (1/12, grade-1), hyponatremia (1/12, grade-1), hypertension (1/12, grade-2), anxiety (1/12, grade-2). Pharmacokinetics of both CBD and THC was less than dose proportional. At the MTD (7.5+7.5), day-1 and day-5 AUC0-24 [median (range)] for CBD were 21.75 (12.44–41.44) ng/ml−1*h and 24.85 (13.72–35.93) ng/ml−1*h respectively. Similarly, for THC, day 1 and day 5 AUC0-24 were 11.79 (8.06–70.58) ng/ml−1*h and 68.98 (1.78 – 136.17) ng/ml−1*h, respectively. Significant accumulation of both CBD and THC was observed across all doses from day 1 to 5. A high variability in pharmacokinetics was observed for both constituents (CV Cmax = 101.26% and 117.48%; CV AUC0-24 = 102.50% and 112.37% for CBD and THC respectively. The median half-life of CBD and THC was 2.2 (1.6–10.7) and 1.9 (1.6–2.4) h respectively. There was no correlation observed between drug exposure and toxicity. There was no significant change in BPRS score before and after IP. Conclusion- We report the first phase-1 study of cannabis in breast and OC-SCC cancer in pre-operative setting for its anti-cancer potential. Biomarker analysis is awaited. MTD identified will be further explored in phase 2/3 clinical trials in breast, oral cavity, lung and pancreatic cancer with survival endpoints. Citation Format: Rajendra Badwe, Shalaka Joshi, Shiva Thiagarajan, Vikram Gota, Vaibhav Vanmali, Pallavi Daphale, Jayita Deodhar, Rohan Chaubal, Rohini Hawaldar, Jaya Chitra Aadhi, Saurabh Kumar Gupta, Delzaad Deolaliwala, Anil Bhansali, Siddhant Mistry, Satyajeet Singh, Nita Nair, Vani Parmar, Sudeep Gupta. Safety and Feasibility of Administration of an Oral Cannabis Preparation in The Preoperative Period in Breast and Oral Cavity Cancer [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 PO4-18-05.

Abstract PO3-13-05: PD-L1 and PD-L2 Protein Expression is Frequently Discordant in Breast Cancer

Abstract Background: In neoadjuvant setting, PD-1 inhibitors have shown significantly higher pathological responses in patients (pts) with early-stage triple-negative breast cancer (TNBC) irrespective of PD-L1 status. However, durable responses are less common in estrogen receptor-positive (ER+) pts. Most breast cancer (BC) clinical trials of PD-1 inhibitors have thus far focused on PD-L1 expression for patient eligibility. The alternative PD-1 ligand, PD-L2, with reported ~4-fold greater affinity for PD-1, has been largely understudied. We recently reported that high cancer cell protein levels of PD-L2 in pts with treatment-naïve ER+ BC was an independent predictor of shorter progression-free survival. PD-L2 expression was significantly high in ER- group as well, however, given the low numbers of ER- pts, the study was not powered enough to determine the correlation of PD-L2 with PFS in the ER- subgroup. These findings suggest that PD-L2 has an important role in BC and combined PD-L1/PD-L2 status may help improve BC pt selection for PD-1 inhibitors. We therefore initiated efforts to determine baseline expression patterns of PD-L1 and PD-L2 in BC. Methods: PD-L1 and PD-L2 protein levels in cancer cells and tumor-infiltrating immune cells were prospectively analyzed by immunohistochemistry (IHC) using validated antibodies in diagnostic core biopsies of 31 consecutive pts diagnosed with localized or locoregional ER+/HER2- BC or TNBC. Percent positivity of PD-L1 and PD-L2 in cancer cells and immune cells was determined by our breast pathologist. Detectable PD-L1 or PD-L2 expression in ≥1% of cancer cells or stromal immune cells was considered positive. Spearman correlation and Wilcoxon paired analyses were used to measure and correlate PD-L1 and PD-L2 protein expression in cancer and immune cells. Results: There was no significant correlation between PD-L1 and PD-L2 expression, neither across all cases (N=31), nor within ER+ (N=22) or TNBC (N=9) cases. However, PD-L1 and PD-L2 expression patterns in BC differed in several ways. PD-L1-positivity in immune cells was higher than in cancer cells (median=5.0% vs. 0.0%; p=0.001), whereas PD-L2-positivity was higher in cancer cells than in immune cells (median=30% vs. 5.0%; p< 0.001). PD-L1 positivity in cancer cells and immune cells were positively correlated in TNBC (rho=0.69, p=0.04) but not in ER+ BC. Conversely, PD-L2 positivity in cancer cells and immune cells were positively correlated in ER+ BC (rho=0.68, p=0.001) but not in TNBC. TNBC diverged from ER+ BC by displaying higher PD-L1 positivity in immune cells (median=20.0% vs. 1.0%; p=0.004). By the conventional cut point for positivity of ≥1% for PD-L1 and PD-L2 in cancer cells or immune cells, all TNBC tumors were PD-L1-positive (9/9), with 8 also being PD-L2-positive. Of the 22 ER+ cases, 16 were PD-L2-positive, of which only 9 were also PD-L1-positive. Table 1. shows cross tabulation data for PD-L1 and PD-L2 status by BC subtype. Conclusions: PD-L1 and PD-L2 proteins show divergent expression and are not correlated in BC. Discordant PD-L2 and PD-L1 expression may be more common in ER+ BC than in TNBC. This finding justifies efforts to explore PD-L2 as a complementary marker to PD-L1 for improved prediction of response to PD-1 inhibitors, which may benefit patients with aggressive ER+ BC that are eligible for chemotherapy. Table 1. PD-L1 vs. PD-L2 Status by Breast Cancer Subtype Citation Format: Lubna Chaudhary, Julie Jorns, Yunguang Sun, Sailaja Kamaraju, Yee Chung Cheng, Amanda Kong, Tina Yen, Caitlin Patten, Chandler Cortina, Inna Chervoneva, Christopher Chitambar, Hallgeir Rui. PD-L1 and PD-L2 Protein Expression is Frequently Discordant in Breast Cancer [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 PO3-13-05.