bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective, multicenter study on non-pharmacological, patient related predictive factors of chemotherapy induced nausea and vomiting (CINV): A NOGGO-EMRISK trial.
Authors: Sehouli Jalid , Oskay-Özcelik Gülten , Zocholl Dario , Klemt Anna-Sophia , Bangemann Nikola , Albrecht Oliver , Strittmatter Hans-Joachim , Wimberger Pauline , Kaczerowsky Anna , Lorenz Ralf , Ruhwedel Wencke , Fehm Tanja N. , Zahn Andreas , Tome Oliver , Markert Miriam , Hager Dietrich , Zorr Andreas , Keller Maren , Rittmeister Hannah , Grabowski Jacek P.
Published: June 2022

e24107

Background: Despite many years of clinical research and development, nausea and vomiting remain challenging toxicities related to chemotherapy. The aim of our study was assessment of non-pharmacological, patient-related risk factors for chemotherapy-induced nausea and vomiting and development of unique predictive score in patients with gynaecological malignancies planned for chemotherapy. Methods: A research-based questionnaire of 27 risk factors was generated and provided to patients diagnosed with gynaecological malignancies prior to indicated chemotherapy. The data on nausea and vomiting from at least 3 cycles therapy was collected. Variable selection via stepwise and LASSO regression combined with patients history was used to identify a small set of questions with high predictive power. As risk prediction model, a Bayesian logistic regression was implemented with a cut-off chosen to yield a sensitivity of 80%. Area under the curve analysis (AUC) was conducted, and accuracy of prediction was calculated. Results: In total 191 patients were enrolled. The most frequent diagnosis and chemotherapy was ovarian cancer (69%) and carboplatinum/paclitaxel combination (57.7%), respectively. Six factors (emetogenic potential of the therapy, educational status, nausea and vomiting due to other medication, motion sickness, anxiety from therapy in general and anxiety from nausea due to therapy) were identified as most important predictive factors. All questions were answered by 132 (69.1%) patients. Among those 97 (68%) reported nausea or vomiting. The AUC of the predictive score consisting mentioned factors was 0.741, with a sensitivity of 80.4%, specificity of 51.4% and an overall accuracy of 72.7%. Conclusions: Patients related risk factors are missing in selection of the antiemetic prophylaxis in patients under chemotherapy. Presented predictive score showed very promising predictive power and is going to be validated in further phase of the trial. Clinical trial information: DRKS-ID: DRKS00015151.
Real-world treatment outcomes and healthcare resource use associated with antiemetics among cancer patients on highly emetogenic platinum-based chemotherapy.
Authors: Navari Rudolph M. , Nelson Winnie , Utt James K , Shoaib-Agwan Sofia , Singh Risho , Zhang Weiping , Bailey William L.
Published: June 2022

e24109

Background: Chemotherapy-induced nausea and vomiting (CINV) is a recognized adverse outcome among cancer patients, and guidelines recommend appropriate prophylactic antiemetics. Highly emetogenic chemotherapy (HEC) is associated with high risk of CINV that potentially lead to additional healthcare resource use. This retrospective study aimed to quantify the treatment outcomes and resource utilization associated with antiemetic use to prevent CINV in a broad US population. Methods: Cancer patients who received platinum–based HEC were identified in the All Payers Claims Database (APCD). The APCD is a database representing the US population with commercial, Medicare, or Medicaid insurance. Insurance claims denote medical care associated with payment, providing an optimal data source to study healthcare resource use. Study patients were age ≥18 years and administered IV 1) fosnetupitant/palonosetron (IV NEPA), 2) aprepitant/fosaprepitant + palonosetron (IV APPA) or 3) aprepitant/fosaprepitant + ondansetron (IV APON) along with HEC. Patients were identified from 1/2016 - 12/2019. The index date was the first treatment date of a study antiemetic. Demographic and clinical characteristics were evaluated in the baseline period, which was 12 months prior to the index date. The post-HEC follow-up period was 14 days, starting the day after each HEC administration. Outcomes were reported descriptively as weighted means, with the cycles of treatment as the unit of analysis, including nausea & vomiting, dehydration, fluid-electrolyte imbalances, and hydration therapy. Results: Study included 1,216 IV NEPA, 43,537 IV APPA, and 16,140 IV APON patients who received HEC. During the post-HEC follow-up period, IV NEPA patients reported fewer occurrences of nausea & vomiting and fluid-electrolyte imbalances per cycle of treatment when compared to IV APPA and IV APON patients. Despite having similar or more dehydration claims for IV NEPA, the occurrence of hydration therapy was lower or similar to the other study groups. (Table). Conclusions: The choice of antiemetics to prevent CINV among cancer patients receiving HEC may impact real-world outcomes and healthcare resource use.[Table: see text]
The outcome and prognostic factors of advanced non-small cell lung cancer patients with do-not-intubation order in intensive care unit.
Authors: Shen Chia-I , Yang Shan-Yao , Chiu Hwa-Yen , Chen Wei-Chih , Yu Wen-Kuang , Yang Kuang-Yao
Published: June 2022

e24113

Background: The survival of lung cancer patients in critical care has been improved. Increasing number of lung cancer patients have signed predefined do-not-intubation (DNI) order before admission to ICU. These patients may still be transferred to ICU and even receive non-invasive ventilation (NIV) supports. However, there is still lack of prognostic prediction in this cohort. Whether patients will be benefit of ICU care remain unclear. Methods: We retrospectively collected data of patients with advanced lung cancer, having signed DNI order before ICU admission in a tertiary medical center. The clinical characteristics and survival outcomes were discussed. The enrollment duration is between 2014 to 2016. Results: Total 140 patients were included. All patients were diagnosed with stage III or IV non-small cell lung cancer (AJCC 7th edition) and signed DNI. The median age was 73 years old and about two-thirds were male. Most patients had received NIV during ICU course. The median APACHE II score was 14 (SE, 0.66) and the mean P/F ratio was 174.2(+/-104) mmHg. The APACHE II score was significantly lower in 28-day survivors (survivor 12 (+/-0.98) vs non-survivor 15 (+/-0.83), p = 0.019). The P/F ratio of the survivors was higher than non-survivors (survivor 209.6+/-111.4 vs non-survivor 157.9+/-96.7, p = 0.006). Patients with P/F ratio ≥150 had better 28-day survival (p = 0.005). By combining P/F ratio≥150 and APACHE II score < 16, those with high P/F ratio and low APACHE II score during ICU admission had a notable 28-day survival compared with the rest (p < 0.001). These prognostic factors could also be applied for 90-day survival (p = 0.003). The prediction model was significant in those with driver mutations in 90-day survival (p = 0.021) but not in those without driver mutations (p = 0.061). Conclusions: The P/F ratio≥150 and APACHE II score < 16 were the prognostic significance of critically ill lung cancer patients with DNI. The prediction could be applied for 90-day survival in patients with driver mutation. The finding was informative for clinical practice and decision-making.
The impact of anthracycline-based chemotherapy on fatigue: Results from WF-97415.
Authors: Avis Nancy E , Levine Beverly J , Mihalko Shannon L. , Klepin Heidi D. , Brubaker Peter H. , Calhoun Tonya , Dent Susan Faye , Hackney Mary Helen , Ky Bonnie , Ladd Amy , Ntim William Ofori , Wagner Lynne I. , Weaver Kathryn E. , Hundley W. Gregory
Published: June 2022

e24115

Background: Chemotherapy (CT) is one of the most common factors associated with fatigue among breast cancer (BC) patients. However, there is a paucity of research on the impact of different types of CT on fatigue, specifically, whether women who receive anthracycline-based (Anth) CT experience greater fatigue than those who receive non-anthracycline-based (noAnth) CT. Methods: Analyses are from the longitudinal Understanding and Predicting fatigue, cardiovascular decline, and events after BrEast cAncer sTudy (UPBEAT: WF 97415)), conducted through the NCI Community Oncology Research Program (NCORP). We compared fatigue 3-months after initiating cancer treatment, controlling for fatigue measured just prior to beginning CT (baseline), in 3 groups of women: BC patients receiving Anth CT (N = 103 at baseline), BC patients receiving NoAnth CT (N = 155), and women without cancer (N = 145). Fatigue was measured by the Functional Assessment of Chronic Illness Therapy Fatigue scale where lower scores indicate greater fatigue. Scores < 30 indicate severe fatigue. We used ANOVA and ANCOVA models (PROC GLM; SAS v. 9.4) to generate unadjusted and adjusted mean fatigue scores in the 3 groups at the relevant time point. Given that selection to CT type was not random, we further adjusted for patient characteristics that influence treatment type (stage and comorbidities) in a model with the two CT groups only. Results: Mean age of participants (75.7% White and 18.1% Black) was 53.9 years. Among BC patients, the Anth group had higher tumor stage compared to the NoAnth group. Both cancer treatment groups reported significantly greater (unadjusted) fatigue pre-chemotherapy and at 3 months than healthy controls, but did not differ from each other. Adjusting for age and baseline fatigue, 3-month fatigue scores were significantly worse for the two CT groups (32.3 for Anth group, 34.3 for the NoAnth group) compared to the controls (44.6) (p < .0001). In a model of cancer patients only, the difference between Anth and NoAnth groups remained non-significant (p = 0.10), after adjusting additionally for number of comorbidities and cancer stage. The unadjusted percentage of women with severe fatigue at 3 months was significantly greater for the BC patients (39% in the Anth group; 38% in the NoAnth group) compared to the healthy controls (1%), but again the two chemotherapy groups were not significantly different from each other. Adjustment for covariates listed above did not change this finding. Conclusions: Analyses support previous studies showing significant fatigue among BC patients treated with CT compared to women without cancer. Our data suggest that fatigue significantly impacts patients receiving CT irrespective of the regimen selected.[Table: see text]
Utilizing an innovative digital collaboration tool to impact shared decision making, health equity and trust with a focus on advance care planning for patients with metastatic breast cancer.
Authors: Harry Kadie , Sykes Arabella , Pluard Timothy J.
Published: June 2022

e24123

Background: Advance care planning (ACP) has been associated with improved quality of life, increased use of hospice and palliative care, and less use of extreme treatments close to death. These conversations often do not occur and documentation rates of ACP in oncology patients have been as low as 10%, with rates of documentation increasing between 30-40% in intervention studies. The present study aimed to examine the effectiveness of an online Advance Care Appointment Companion (ACAC) collaboration tool to improve communication and elevate trust between MBC patients and their oncologist and increase completion rates of ACP documents. Methods: Data were collected from 48 patients with mean age of 66.9 years (SD = 6.97) with MBC during their medical oncology appointments (Time 1) and three months later (Time 2) at the Koontz Center for Advanced Breast Cancer. At Time 1, patients were enrolled on the ACAC platform and then completed questions in the clinic or at home about completion status of a healthcare directive and durable power of attorney (DPOA) for healthcare, comfort in discussing ACP with their care team and loved ones, and goals of care at end of life. A summary of these responses with a provider prompt script was securely sent to the oncologist prior to each appointment and used to discuss ACP over the three-month study period. Descriptive statistics, t-tests, McNemar-Bowker and McNemar’s tests were conducted to examine changes in rates of ACP document completion, patient reported levels of comfort in discussing ACP, and quality of life preferences. Results: The study included a diverse sample of female MBC patients including 79% White, 19% Black/African American, 2% Mixed Race; 6% less than a high school degree, 17% high school or GED, 19% some college, and 58% associate’s degree or above. Results showed a significant increase in completion of a healthcare directive (Time 1 = 10.4%, Time 2 = 37.5%, p < .01) and DPOA (Time 1 = 31.5%, Time 2 = 56.3%, p < .01) and improved comfort discussing ACP with their care team (p < .01) and loved ones (p < .01) from baseline to follow-up. Significantly more patients reported that they would not want CPR (p < .05) at follow-up and all of these patients had reported that they were unsure at baseline. On average, ACP conversations during medical appointment took 5 minutes to discuss. Conclusions: Results show that the ACAC is an inclusive solution which provides equitable access to patients. This tool facilitates enhanced patient provider communication and assists patients with MBC in finalizing decisions regarding their goals of care, leading to increased completion and proper submission of ACP documentation. Future research should examine how the ACAC can decrease financial toxicity, utilize internal resources, and address social determinants of health.
Associations between cancer history, social distancing behaviors, and loneliness in adults during the COVID-19 pandemic.
Authors: Yang Jenny , Zhang Xiaochen , Yu Ivy , Fisher James L. , DeGraffinreid Cecilia , Paskett Electra D.
Published: June 2022

e24124

Background: Due to COVID-19, social distancing initiatives have been enacted, highlighting differences of social distancing practices and the resulting loneliness in various populations, especially in those with a history of cancer (survivors and those in active treatment).The objective of this study was to examine whether social distancing practices and loneliness differ between individuals with and without a history of cancer during the COVID-19 pandemic. Methods: This study is part of the “Impact of COVID-19 on Behaviors across the Cancer Control Continuum in Ohio” project conducted from June to November 2020. Participants from previous studies (N = 32,989) who had given permission to be re-contacted were invited to complete a survey online, by phone, or by mail. For the current analysis, participants who had complete data on history of cancer diagnosis, COVID social distancing behaviors (staying at home, not having visitors, staying 6 feet apart, wearing a masking indoors, and wearing a mask outdoors), attendance at social gatherings, contact with people outside of their household, and feelings of loneliness were included. Linear and logistic regression models were used to determine the associations between demographics, cancer history, social distancing, and loneliness. Results: Among the eligible participants (n = 5729), 54.9% had a cancer history (n = 3147), while 45.1% did not have a cancer history (n = 2582). The average age was 56.7 years, 35.6% were male, 89.4% were White, 74.7% were partnered, and 74.5% lived in metro counties. Out of all individuals, 69.3% participated in ≥4 of the 5 COVID social distancing behaviors, 31.5% did not attend any social gatherings, and 40.1% reported feeling lonely. Compared to individuals without a cancer history, individuals with a cancer history were more likely to contact no one outside of the household (49.0% vs. 41.9%, p < 0.01) and less likely to report feeling lonely (35.8% vs. 45.3%, p < 0.01). Among individuals with a cancer history, compared to their counterparts, those who were older, Black, Asian, and living in metro counties were adherent to more social distancing behaviors (mean differences = 0.02, 0.62, 0.71, 0.13, respectively, p all < 0.05) and attended fewer social gathering (mean differences = -0.01, -0.29, -0.49, -0.12, respectively, p all < 0.05). Higher adherence to social distancing behaviors was associated with higher odds of loneliness among individuals with (OR = 1.27, 95% CI: 1.72-1.38) and without a cancer history (OR = 1.15, 95% CI: 1.06-1.25). Conclusions: Social distancing practices and loneliness during the COVID-19 pandemic varied between individuals with and without a cancer history. These findings can inform efforts to support and address all aspects of health among individuals susceptible to loneliness during the pandemic, especially those with a history of cancer.
The psychosocial impact of the Australian Rare Cancer Portal on patients with rare cancer.
Authors: Papadopoulos Lia , Georgiou Chloe L. , Kee Damien , Caldwell Reece , Bourne Allison , Haurat Javier , Turner Maureen , Goldstein David , Scott Clare L.
Published: June 2022

e24127

Background: Patients with a rare cancer (RC) diagnosis face unique challenges affecting psychological wellbeing. Vast geographical distances further compound challenges in accessing RC sub-specialist expertise, clinical trials, research and non-reimbursed therapies. The Australian Rare Cancer (ARC) Portal is a novel model of care delivery that has a positive psychological impact on these patients. Methods: The ARC Portal is a national free online referral platform implemented to overcome barriers to accessing excellent care. It is funded by Omico, with support from BioGrid Australia, Rare Cancers Australia (RCA), and The WEHI Stafford Fox Rare Cancer Program (SFRCP). We have recorded 924 referrals for a diverse range of RC in early (30%) and late stages (70%). Our 162 referring clinicians derive from every Australian state and from both regional and metropolitan centres. Over 50 content experts from Australia and internationally have provided case advice. Referring clinical impact surveys and patient feedback surveys were analysed to identify psychosocial impacts of the ARC Portal. Results: Our model of care keeps patients with their primary oncologists by equipping referrers with increased expertise drawing from, on average, two to five experts. The entirely online consent process overcomes geographical barriers to enrolment, and is of particular importance in the context of the ongoing COVID-19 restrictions removing in person interaction. Provision of expertise and treatment recommendations meets informational needs and increased the patient confidence patients in their treating clinicians. Report recommendations directly altered the treatment delivered to patients in 20/48 of surveyed referrer respondents. Early stage patients are eligible for referral to guide neoadjuvant and adjuvant therapy, and those in remission for anticipatory identification of next lines of therapy. We identify appropriate access to investigator-driven research efforts to overcome financial barriers to genomic sequencing e.g. via the MoST Program funded by OMICO and the WEHI-SFRCP enabling access to molecularly-guided therapy. A lack of reimbursed therapeutic options in RC poses financial stress on patients. The ARC Portal expands patients’ treatment options via links with clinical trial networks, coordination with industry, and cross-referral to the charity, RCA, for fundraising assistance. We provide patients with the opportunity for involvement in research, which for many provides hope, either for themselves, or for others, as they can opt to provide access to biomarker and tumour specimens via the WEHI-SFRCP; the majority of patients (82.5%) have provided consent. Conclusions: The ARC Portal offers patients access to excellent rare cancer care resulting in positive impacts upon patients’ psychological wellbeing. These initial observations require more formal assessment.
The effect of group psychotherapy on quality of life of cancer patients undergoing chemotherapy or endocrine therapy during Covid-19 pandemic: One center experience.
Authors: Abuladze Mariam , Esakia Tamar , Cholikidze Tamta , Barabadze Ketevani , Saganelidze Khatuna
Published: June 2022

e24133

Background: The announcement of the pandemic by WHO had a great impact on global mental health. Mental disorders like stress, anxiety, depressive symptoms, insomnia, denial, anger, and fear affected the population worldwide. Cognitive-behavioral techniques are effective in improving the control of symptoms, the affective state and coping with the disease. Methods: Female patients were offered to take part in the study by their oncologists. Inclusion criteria included female patients who were diagnosed with cancer during the last 5 years. Intervention included - Online group psychotherapy which was conducted for 3 consecutive months, three times per week, using the interactive ZOOM platform. The Research and Treatment of Cancer (EORTC) quality of life questionnaire QLQ-C30 was used to assess QoL of participants. We asked patients to fill the ERTC questionnaire twice, before the first and after the last psychotherapy sessions. Results: Total of 25 patients aged 18-55 were included in the study, 72% were receiving hormonal therapy, and 28% were receiving chemotherapy. Majority of patients (18) were diagnosed with breast, 4 with cervical and 1 with uterine and 2 with ovarian cancer in last 5 years. All patients were white Caucasian females. Analysis of Variance (ANOVA) showed no difference between groups on pre-RS score; But the study showed significant improvement in post RS (EORTC QLQ-C30) in patients with hormone therapy (Goodness of Fit-R square-0.4471, P-value-0.0024, 95% Confidence Intervals-0.4200 to 1.626), compare to patients with chemotherapy (Goodness of Fit-R square-0.003372, P-value- 0.9016, 95% Confidence Intervals--1.743 to 1.929).All measures were presented as mean with standard deviation and the level of significance was defined as DELTA(D) = 0.05. Conclusions: According to our research, group psychotherapy had a positive effect on quality of life of cancer patients undergoing hormonal therapy and showed no significant impact on patients treated with chemotherapy. More research and a larger sample size is needed for a better interpretation of results.
Naxitamab and granulocyte macrophage colony stimulating factor (GM-CSF) in combination with irinotecan and temozolomide in patients with high-risk neuroblastoma with primary refractory disease or in first relapse: An international, single-arm, multicenter phase 2 trial.
Authors: Chan Godfrey Chi-Fung , Hindsberger Charlotte , Morsing Anni , Lisby Steen
Published: June 2022

TPS10061

Background: Neuroblastoma (NB) is the commonest extracranial solid tumor in children. At diagnosis, > 50% have high-risk (HR) disease with poor prognosis despite intensive therapy; thus, there is a high unmet medical need. Naxitamab is an anti-GD2 monoclonal antibody indicated under accelerated approval in the US with GM-CSF for the treatment of relapsed/refractory HR NB in the bone and/or bone marrow in patients (pts) ≥1 year of age with a partial response, minor response, or stable disease to prior therapy. Irinotecan and temozolomide (IT) are commonly used salvage chemotherapies following failure of frontline therapy. The objective of this study is to investigate the efficacy and safety of naxitamab plus IT in pts with HR NB with primary refractory disease or first relapse. Methods: Trial 203 (NCT04560166) is an international, single-arm, multicenter phase 2 trial for HR NB patients ≥12 mo of age, with either evaluable primary refractory disease or first relapse following induction and consolidation therapy. The primary endpoint of the study is the centrally-assessed overall response rate (ORR) (complete [CR] or partial response) at or before completion of 4 cycles of treatment. Key secondary endpoints include ORR after 2 cycles of treatment, duration of response (DoR), CR rate, time to first subsequent therapy or death, progression-free survival (PFS), and overall survival (OS). 52 pts will be enrolled to provide 82% power to demonstrate that response rate is significantly higher than 20%. Key inclusion criteria are documented HR NB at time of diagnosis; received frontline induction/consolidation therapy; active disease despite previous aggressive chemotherapy; and measurable tumor (CT/MRI) that is either MIBG-avid/PET-positive or have MIBG scan with uptake at ≥1 site. Key exclusion criteria include prior treatment with duration ≤3 wks (chemotherapy), ≤6wks (autologous stem cell transplant or therapeutic 131I-MIBG), ≤4wks (radiation therapy), or progressed while on anti-GD2; residual NB in the bone marrow only; and CNS/leptomeningeal disease in the prior 6 mo. In addition, there should not be < 50% performance status per Lansky or Karnosky scale and life expectancy < 6 mo. Pts will receive irinotecan 50 mg/m2/day IV and temozolomide 100 mg/m2/day orally (both on Days 1-5) in combination with naxitamab 2.25 mg/kg/day IV (Days 2, 4, 8 and 10) and GM-CSF 250 ug/m2/day sc (Days 6-10) in 21 days cycle. Response rates will be assessed using the 2-sided binomial test at the 5% significance level; DoR, PFS, and OS will be estimated using Kaplan-Meier analysis. Adverse events will be graded per CTCAE. Clinical trial information: NCT04560166.
A pilot clinical study of VAL-413 (oral irinotecan HCl) in patients with recurrent pediatric solid tumors.
Authors: Brown Dennis , Bacha Jeffrey A. , Geller James I. , Thompson Patrick A. , Oesterheld Javier E. , Kanekal Sarath , Leggas Markos , Lopez Lorena , Sankar Neil , Yam Noymi , Wagner Lars M.
Published: June 2022

TPS10063

Background: Intravenous irinotecan hydrochloride (IRN-IV) is approved for the treatment of adult colorectal cancer. IRN-IV is also widely used off-label for a range of adult and pediatric solid tumors including recurrent Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, hepatoblastoma, Wilms tumor, gynecologic cancers, lung cancer and medulloblastoma. Previously, a regimen of IRN-IV administered as a 60-min i.v. infusion daily for 5 days, every 21 days has been recommended use in treating children with solid tumors (Blaney. ClinCanRes, 2001 ). Protracted administration schedule of intravenous irinotecan is inconvenient for patients, so oral regimens utilizing IRN-IV have been developed (Wagner. ClinSarcRes, 2015 ). Unfortunately, the palatability of the intravenous preparation is poor, leading to reduced compliance especially in younger pediatric patients. Development of an advanced formulation to improve tolerability and patient compliance is an important unmet clinical need. VAL-413 is a novel formulation developed to improve palatability of oral irinotecan. Methods: Eligibility: Up to 20 patients ≥ 1 year and ≤ 30 years of age with recurrent pediatric solid tumors and adequate bone marrow, renal and liver function, for whom irinotecan therapy is a treatment option will be enrolled. Trial Design: Two different dose levels of VAL-413, 90mg/m2/day or 100mg/m2/day will be studied in combination with a fixed-dose of temozolomide using a standard 3 + 3 phase I design. In the event that the starting dose of 90 mg/m2/day is not tolerable due to toxicity, a lower dose of 75 mg/m2/day may be implemented. Treatment: During the first cycle of treatment, each patient will receive 4 daily doses of VAL-413 and one daily dose of the intravenous preparation of irinotecan taken orally (IRN-IVPO). During all subsequent cycles, only VAL-413 will be given with temozolomide in 5-day courses administered every 21 days, as tolerated. Outcome Measures: Toxicity is assessed by NCI CCTCAEv5; tumor response is assessed by RECIST 1.1. A palatability survey instrument will assess palatability of VAL-413 vs. IRN-IVPO; and comparative intrapatient pharmacokinetics of irinotecan and its metabolites will be assessed in all patients. This trial is ongoing (CT.gov: NCT04337177). Enrolment of the first dose level is ongoing, with no DLT observed to date. Clinical trial information: NCT04337177.
A randomized, multicenter, placebo-controlled, phase III study to evaluate the efficacy and safety of HER2/neu peptide GLSI-100 (GP2 + GM-CSF) in patients with residual disease or high-risk PCR after both neo-adjuvant and postoperative adjuvant anti-HER2 therapy, Flamingo-01.
Authors: Patel Snehal , Thompson Jaye , Patel Mira , Daugherty F. Joseph , Osborne C. Kent , Rimawi Mothaffar F.
Published: June 2022

TPS1110

Background: GP2 is a biologic nine amino acid peptide of the HER2/ neu protein delivered in combination with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) that stimulates an immune response targeting HER2/neu expressing cancers, the combination known as GLSI-100. In a prospective, randomized, single-blinded, placebo-controlled, multicenter Phase IIb study, no recurrences were observed in the HER2+ population after 5 years of follow-up, if the patient was treated with GLSI-100, survived and was followed from more than 6 months ( p = 0.0338). Immunotherapy elicited a potent response measured by skin tests and immunological assays. Of the 146 patients that have been treated with GLSI-100 over 4 clinical trials, GLSI-100 was well-tolerated and no serious adverse events were observed considered related to the immunotherapy. Methods: This Phase 3 trial is a prospective, randomized, double-blinded, multi-center study. After 1 year of trastuzumab-based therapy, 6 intradermal injections of GLSI-100 or placebo will be administered over the first 6 months and 5 subsequent boosters will be administered over the next 2.5 years for a total of 11 injections over 3 years. The participant duration of the trial will be 3 years treatment plus 1 additional year follow-up for a total of 4 years following the first year of treatment with trastuzumab-based therapy. Patients will be stratified based on residual disease status at surgery, hormone receptor status and region. Approximately 498 patients will be enrolled. To detect a hazard ratio of 0.3 in invasive breast cancer free survival (IBCFS), 28 events will be required. An interim analysis for superiority and futility will be conducted when at least 14 events have occurred. This sample size provides 80% power if the annual rate of events in placebo patients is 2.4% or greater. Up to 100 non-HLA-A*02 subjects will be enrolled in an open-label arm. Eligibility Criteria: The patient population is defined by these key eligibility criteria: HER2/neu positive and HLA-A*02; Residual disease or High risk pCR (Stage III at presentation) post neo-adjuvant therapy; Exclude Stage IV; Completed at least 90% of planned trastuzumab-based therapy. Trial Objectives: To determine if GP2 therapy increases IBCFS; To assess the safety profile of GP2; To monitor immunologic responses to treatment and assess relationship to efficacy and safety. Accrual: Site selection and study start-up is in progress at multiple sites. Target enrollment is 598 subjects. Clinical trial information: 05232916.
ARV-471, an estrogen receptor (ER) PROTACdegrader, combined with palbociclib in advanced ER+/human epidermal growth factor receptor 2–negative (HER2-) breast cancer: Phase 1b cohort (part C) of a phase 1/2 study.
Authors: Hamilton Erika P. , Schott Anne F. , Nanda Rita , Lu Haolan , Keung Chi Fung , Gedrich Richard , Parameswaran Janaki , Han Hyo S. , Hurvitz Sara A.
Published: June 2022

TPS1120

Background: ARV-471 is a novel, potent, orally bioavailable PROteolysis TArgeting Chimera (PROTAC) protein degrader that selectively targets the ER. In xenograft models, ARV-471 demonstrated substantially greater ER degradation and antitumor activity compared with the selective ER degrader fulvestrant. In the phase 1 dose escalation portion (Part A) of the first-in-human phase 1/2 study, ARV-471 monotherapy was well tolerated and showed antitumor activity in patients with ER+/HER2- locally advanced or metastatic breast cancer who had previously received endocrine therapy and a cyclin-dependent kinase (CDK)4/6 inhibitor; the clinical benefit rate (rate of confirmed complete or partial response or stable disease ≥24 weeks) was 40% (95% CI: 26%–56%) in 47 evaluable patients. The phase 2 VERITAC expansion cohort (Part B) is further evaluating ARV-471 monotherapy in this patient population. Palbociclib, a CDK4/6 inhibitor, plus fulvestrant is a standard treatment option for patients with ER+/HER2- breast cancer who have had disease progression on endocrine therapy. ARV-471 plus palbociclib resulted in substantially greater tumor growth inhibition in xenograft models compared with palbociclib plus fulvestrant, supporting further investigation of the ARV-471 plus palbociclib combination in patients with ER+ breast cancer. Here we describe Part C of the phase 1/2 study, which evaluates the safety and clinical activity of ARV-471 plus palbociclib in patients with breast cancer who previously received endocrine therapy. Methods: Eligible patients (aged ≥18 years) have histologically or cytologically confirmed ER+/HER2- advanced breast cancer and have received ≥1 prior endocrine therapy and ≤2 prior chemotherapy regimens for advanced disease; prior CDK4/6 inhibitor therapy is permitted. Patients with known symptomatic brain metastases requiring steroids are excluded. ARV-471 and palbociclib will be administered orally once daily in 28-day cycles; ARV-471 will be given continuously and palbociclib for 21 days followed by 7 days off treatment. Primary objectives are to evaluate the safety and tolerability of ARV-471 plus palbociclib and select the recommended phase 2 dose and schedule of the combination (based on the incidence of dose-limiting toxicities during the first cycle and the frequency and severity of adverse events and laboratory abnormalities). Secondary objectives are to assess preliminary antitumor activity of ARV-471 plus palbociclib (based on overall response rate per Response Evaluation Criteria in Solid Tumors v1.1, clinical benefit rate, progression-free survival, and duration of response) and pharmacokinetic parameters. Clinical trial information: NCT04072952.
Phase Ib/II study of BCL-2 inhibitor lisaftoclax (APG-2575) safety and tolerability when administered alone or combined with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor in patients with estrogen receptor-positive (ER+) breast cancer or advanced solid tumors.
Authors: Kalinsky Kevin , Tolcher Anthony W. , Wang Shushen , Meric-Bernstam Funda , Winkler Robert , Li Mingyu , Sun Xuemei , Pan Wentao , Paudyal Bishnuhari , LIANG ZHIYAN , Lu Ming , Yang Dajun , Zhai Yifan
Published: June 2022

TPS1122

Background: Various cancers evade apoptosis by overexpressing BCL-2 proteins. Investigational agent lisaftoclax (APG-2575) is a novel, potent, selective BCL-2 inhibitor, while palbociclib inhibits cyclin-dependent kinases (CDK) 4 and 6. In preclinical studies, palbociclib decreased proliferation of ER+ breast cancer cell lines by arresting them in the G1 cycle phase. Preclinical data demonstrate favorable, complementary effects of palbociclib when combined with a BCL-2 inhibitor and support this combination in patients with ER+/ human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer. Methods: This global multicenter open-label dose escalation and dose expansion study is assessing the safety of lisaftoclax monotherapy in patients with histologically or cytologically confirmed advanced solid tumors that have progressed on standard therapy or when combined with CDK4/6 inhibitor palbociclib in physiologically postmenopausal women with ER+/ HER2- metastatic breast cancer that has progressed or relapsed after treatment with a CDK4/6 inhibitor. This trial consists of 2 parts: a phase Ib dose escalation phase using a standard 3+3 design to determine the maximum tolerated dose (MTD) of lisaftoclax as a single agent in patients with solid tumors, as well as both the MTD and recommended phase 2 (RP2D) dose of lisaftoclax when combined with palbociclib in women with ER+/ HER2- metastatic breast cancer. Phase II of this study is a signal-seeking expansion of lisaftoclax at RP2D when combined with palbociclib in women with ER+/HER2- metastatic breast cancer. This phase is being conducted using Simon’s Minimax two-stage design. The primary objective for phase II is to determine clinical benefit response, and secondary efficacy endpoints include overall response rate, duration of response, time to response, and progression-free survival. Lisaftoclax is being administered orally once daily in a 28-day cycle at the assigned dose. Clinical trial information: NCT04946864.
MOTION: A randomized, phase 3, placebo-controlled, double-blind study of vimseltinib (DCC-3014) for the treatment of tenosynovial giant cell tumor.
Authors: Tap William D. , Wagner Andrew J. , Sharma Maitreyi G. , Vallee Marc , Michenzie Mary F. , Sherman Matthew L. , Ruiz-Soto Rodrigo , Stacchiotti Silvia , van de Sande Michiel A.J. , Gelderblom Hans
Published: June 2022

TPS11590

Background: Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive neoplasm that occurs in the synovium of joints, bursae, or tendon sheaths. TGCT is caused by upregulation of the colony-stimulating factor 1 (CSF1) gene, resulting in aberrant CSF1 expression and the recruitment of CSF1 receptor (R)-dependent inflammatory cells. Resection is the primary treatment, but nonsurgical treatment options are necessary for patients with symptomatic TGCT not amenable to surgical resection. Vimseltinib is an oral switch control TKI specifically designed to selectively and potently inhibit CSF1R. In a Phase 1/2 study in patients with TGCT, vimseltinib showed encouraging antitumor activity with an overall objective response rate (ORR) of 42% in the cohort receiving 30 mg twice weekly (recommended phase 2 dose; Gelderblom et al, ESMO 2021 Poster). Vimseltinib was also well tolerated, and the majority of the common (≥15%) treatment-emergent adverse events (TEAEs) were Grades 1–2. Among these common TEAEs, the only Grade 3–4 event in the Phase 2, twice-weekly, 30-mg cohort was increased blood creatine phosphokinase (CPK); however, this elevated CPK was not associated with any symptoms (Gelderblom et al, ESMO 2021 Poster). Phase 1/2 efficacy and safety data support further development of vimseltinib; here, we describe the ongoing Phase 3 study for patients with TGCT not amenable to surgical resection. Methods: MOTION (NCT05059262) is a Phase 3, randomized, placebo-controlled, double-blind study that aims to evaluate the efficacy and safety of vimseltinib for the treatment of TGCT not amenable to surgical resection. Participants must be at least 18 years of age and have histologically confirmed and symptomatic TGCT for which surgical resection will potentially cause worsening functional limitation or severe morbidity. Prior CSF1R therapy is not permitted (previous imatinib and nilotinib is allowed). In Part 1 of the study, eligible participants will be randomized 2:1 to receive either vimseltinib 30 mg twice a week or matched placebo for 24 weeks. The primary outcome measure is ORR assessed by central read using Response Evaluation Criteria in Solid Tumors version 1.1 at 25 weeks. Secondary outcome measures include ORR per tumor volume score, range of motion, and patient-reported outcomes. Participants assigned to placebo in Part 1 will have the option to receive vimseltinib in Part 2, a long-term treatment phase in which participants will receive open-label vimseltinib. This international study plans to randomize 120 participants and is currently enrolling. Clinical trial information: NCT05059262.
Targeting adiposity and inflammation with movement to improve prognosis in breast cancer survivors (the AIM trial): Rationale, design, and methods.
Authors: Dieli-Conwright Christina Marie , Kang Dong-Woo , Wilson Rebekah M , Gonzalo-Encabo Paola , Norris Mary , Hans Marybeth , Tahbaz Meghan , Dawson Jackie , Nguyen Danny , Normann Amber , Yunker Alexandra G , Sami Nathalie , Uno Hajime , Ligibel Jennifer A. , Mittelman Steven D
Published: June 2022

TPS12140

Background: Obesity is considered a leading modifiable contributor to breast cancer mortality worldwide due to its association with increased recurrence and decreased overall survival rate. A central mechanism by which obesity stimulates cancer progression is through chronic, low-grade inflammation in adipose tissue. Exercise has shown potential in improving inflammation but has not been implemented with breast cancer survivors. Our hypothesis is that exercise designed to target chronic inflammation and associated sarcopenic obesity will improve prognosis in obese breast cancer survivors. Methods: The AIM trial is a prospective, three-armed, phase II randomized controlled trial investigating the effects of a 16-week supervised circuit aerobic and resistance exercise (CARE) program compared to a traditional aerobic and resistance exercise (TARE) program, and attention control (AC) group, on adipose tissue inflammation in 300 breast cancer survivors. Main inclusion criteria are histologically confirmed breast cancer stage 0-III, completion of chemotherapy and/or radiation, sedentary, centrally obese, and free from musculoskeletal disorders. The primary endpoint is adipose tissue inflammation as assessed by core biopsy and blood draw; secondary endpoint is sarcopenic obesity; and exploratory endpoints are physical fitness and function and patient reported outcomes. Participants randomized to the exercise groups participate in three weekly supervised exercise sessions for 16-weeks. Participants randomized to the attention control group are offered the CARE intervention after the 16-week period of observation. Discussion: This is the first randomized controlled trial examining the effects of exercise on adipose tissue inflammation in obese, breast cancer survivors. Results will contribute to a better understanding of exercise modality on adipose tissue inflammation that can potentially improve patient prognosis. Clinical trial information: NCT03091842.
A phase 0/surgical window-of-opportunity study in progress, evaluating evolocumab in patients with high-grade glioma or glioblastoma.
Authors: Singh Kirit , Foster Matthew , Miller Elizabeth S. , Gregory Simon , Weinhold Kent J. , Ashley David M. , Desjardins Annick , Low Justin , Peters Katherine B. , Severance Erin , Jaggers Denise , Friedman Henry S. , Johnson Margaret O. , Friedman Allan H. , Keir Stephen T. , Herndon James Emmett , Li Chuan-Yuan , Fecci Peter E. , Sampson John H. , Khasraw Mustafa
Published: June 2022

TPS2076

Background: High-grade gliomas (HGGs) are immunologically ‘cold’ tumors. This phenomenon is partly due to reduced expression of major histocompatibility class (MHC) I on the surface of tumor cells, which prevents CD8+ cytotoxic T lymphocyte activity (CTLs). Blockade of proprotein convertase subtilisin/kexin type 9 (PCSK9) increases MHC class I expression, enhances CTL tumoral infiltration, and potentiates checkpoint inhibition in vivo. Evolocumab is an FDA-approved fully human IgG2 monoclonal antibody PCSK9 inhibitor which is clinically indicated for hyperlipidemia. This study seeks to determine whether evolocumab can cross the blood-brain barrier (BBB) and enhance MHC I expression on resected tumor cells, serving as a potential future adjunct for immunotherapy. Methods: This study will enroll ten patients over 18 years who have newly diagnosed or recurrent HGG. These patients will also need to be undergoing resection of their tumor as part of their planned treatment pathway. Following informed consent, patients will receive evolocumab (420mg, subcutaneously) 7-14 days before surgical debulking of the tumor. We will collect tissue which is not required for histological tumor analysis and compare it with a contemporaneous matched control cohort. This will consist of resected tumor specimens from patients not treated with evolocumab. Quantification of the drug will be performed using mass spectroscopy, flow cytometry, and single-cell sequencing. The primary objective of this study is to evaluate whether evolocumab can cross the BBB and be measured in resected tumor specimens taken from patients with HGG. Secondary objectives include an analysis of lipid metabolism and MHC-I expression on the tumor via flow cytometry and CITEseq. Wilcoxon rank-sum test or a two-sample t-test, will compare groups for these endpoints. Exploratory analyses will determine if evolocumab leads to changes in tumorigenic pathways and the immune profile of tumor infiltrating lymphocytes (TILs). Bioinformatic analyses will be performed using protein set enrichment, gene ontology (GO) annotations, and search tools from the retrieval of interactive genes/proteins (STRING). Progress: The study was activated on 10/04/2021 (NCT04937413) and at the time of submission has enrolled 5 participants (4 to control arm, 1 to intervention arm). Clinical trial information: NCT04937413.
ARTISTRY-3: Effect of nemvaleukin alfa with a less frequent IV dosing schedule as monotherapy and in combination with pembrolizumab and impact on the tumor microenvironment (TME) in patients (pts) with advanced solid tumors.
Authors: Piha-Paul Sarina Anne , Elliott Corrine F. , Du Yangchun , Graham Julie R. , Desai, MD Monali , Wang Yan , Dalal Rita P. , Lakhani Nehal J.
Published: June 2022

TPS2684

Background: Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel engineered cytokine that selectively binds the intermediate-affinity interleukin-2 (IL-2) receptor, preferentially activating and expanding antitumor CD8+ T cells and NK effector cells, with minimal effect on regulatory T cells. Nemvaleukin was designed to leverage antitumor effects of the IL-2 pathway while limiting typical IL-2‒associated toxicity. In ARTISTRY-1, the recommended phase 2 dose (RP2D) for nemvaleukin monotherapy of 6 µg/kg IV on days 1 to 5 of a 21-day cycle elicited durable and deep responses in pts with advanced melanoma and renal cell carcinoma (Boni et al. ASCO 2021:abstr 2513). Responses with nemvaleukin plus pembrolizumab were also observed in platinum-resistant ovarian, breast, cervical, gastrointestinal, and genitourinary cancers. ARTISTRY-3 will investigate the effects of nemvaleukin as monotherapy and in combination with pembrolizumab on the TME in pts with advanced solid tumors, and in an additional cohort (Cohort 2), to further assess a less frequent IV dosing schedule for nemvaleukin. Methods: The phase 1/2, open-label ARTISTRY-3 (NCT04592653) study will enroll adults (≥18 years) with select advanced solid tumors, ≥1 accessible lesion for biopsy, ≥1 target lesion (per RECIST v1.1), ECOG PS of 0 or 1, estimated life expectancy of ≥3 months, adequate hematologic reserve, and adequate hepatic and renal function. Primary objectives: to evaluate effects of nemvaleukin monotherapy on the TME (Cohort 1) and to determine RP2D for less frequent dosing schedule (Cohort 2). Additional objectives are to evaluate: efficacy, safety, immunogenicity, and pharmacokinetics of nemvaleukin monotherapy; effects of nemvaleukin plus pembrolizumab on the TME; and correlative biomarkers of nemvaleukin as monotherapy and combination. Following the protocol amendment, additional pts enrolled in Cohort 1 will receive lead-in monotherapy at a dose selected based on results from Cohort 2, and pre- and on-treatment biopsies will be collected for TME assessments. Subsequent cycles will be administered in combination with pembrolizumab, and a biopsy may be collected at cycle 4 or 5. Tumor types eligible for Cohort 2 are selected based on activity observed in the ARTISTRY-1 study. A quantitative system pharmacology model was applied to identify a less frequent schedule for nemvaleukin monotherapy and combination. Cohort 2 will initially assess safety and tolerability of nemvaleukin at 1 dose per 21-day cycle. Two doses per 21-day cycle may be implemented to achieve optimal PK/PD parameters. Bayesian optimal interval design methodology with open enrollment will be applied to facilitate dose escalation decisions. Clinical trial information: NCT04592653.