bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of everolimus-containing chemotherapy in HER2 negative metastatic breast cancer patients with PI3K/AKT/mTOR mutations: A retrospective study.
Authors: Wang Rong , Wang Xiaojia , Chen Zhan-hong , Niu Jin , Huang Yuan , Pan Jiani , Ye Weiwu , Cao Wenming
Published: June 2021

e13069

Background: The PI3K/AKT/mTOR pathway is frequently altered in breast cancer. Everolimus is a selective inhibitor of mammalian target of Rapamycin (mTOR).The benefit of everolimus in metastatic breast cancer patients with PI3K/AKT/mTOR mutations remains unclear, especially in TNBC patients. Our study aimed to investigate the efficacy of the everolimus-containing chemotherapy in metastatic breast cancer patients with PI3K/AKT/mTOR mutations. Methods: 13 cases of HER2- metastatic breast cancer with PI3K/AKT/mTOR mutations treated with everolimus-containing chemotherapy were analyzed. The genetic profile in PI3K/AKT/mTOR pathway was studied. Results: Overall, 4 cases were hormone receptor (HR) positive and 9 were TNBC. 7 patients only had PIK3CA mutations, 1 patient had only PIK3R1 mutations, and 5 patients had other mutations in the pathway in addition to PIK3CA, including PTEN, PIK3CB, CTNNB1, FGFR1 and TSC2. 5 cases were treated as first or second line chemotherapy, and 8 were as third line or above. The ORR (CR+PR) was 38.5% (5/13), and DCR (CR+PR+SD) was 84.6% (11/13), including 5 cases of PR, 6 cases of SD, and 2 cases of PD. The median PFS was 5.8 months (95% CI 3.7-9.7), and the median OS was 14.3 months (95% CI 6.47-null). However, the ORR of TNBC patients was higher than that of HR-positive, which were 44.4% (4/9) and 25% (1/4), respectively ( p = 0.070). The mPFS was also longer than that of HR-positive with 5.8 months versus 1.7 months, as well as the mOS with 14.3 versus 3.8 months. We also found that the patients carrying other mutations besides PIK3CA in the PI3K/AKT/mTOR pathway had a longer PFS compared to the patients without other mutations, which was 9.7 months and 4.3 months respectively ( p = 0.272). And the DCR of the two groups were 100% and 75% respectively ( p = 0.451). Conclusions: We found that everolimus-containing chemotherapy was effective in the treatment of HER2- metastatic breast cancer with PI3K/AKT/mTOR pathway activation. TNBC patients had a trend of longer mPFS than HR+ patients. And the patients carrying other mutations besides PIK3CA in the PI3K/AKT/mTOR pathway have a trend of longer PFS and higher DCR compared to the patients without other mutations. However, trails with larger samples are needed for further verification.
Optimizing chair time in infusion centers using intravenous cetirizine premedication for the prevention of hypersensitivity infusion reactions.
Authors: Peguero Julio Antonio , Ayad Ahmed , Young-Wesenberg Stacia , Yang Teresa , North Janine , Joseph-Ridge Nancy
Published: June 2021

e13508

Background: Oncology infusion centers are increasingly focused on improving operational efficiencies and patient satisfaction, while maintaining quality care. One key component is optimizing chair time, which has been especially important for patient safety during the COVID-19 pandemic to reduce risk of transmission. Many infusions require antihistamine premedication to reduce the risk of hypersensitivity infusion reactions (IRs). The two IV options are IV diphenhydramine and IV cetirizine, which have a quicker onset than oral options and can be administered IV push. In treating acute urticaria, IV cetirizine was shown to be comparable to IV diphenhydramine, with fewer side effects, and it may be effective for preventing IRs with improved chair time. Methods: A randomized, double-blind phase 2 study evaluating premedication with single dose IV cetirizine 10 mg versus IV diphenhydramine 50 mg was conducted in 34 patients receiving paclitaxel, rituximab, its biosimilar or obinutuzumab (first cycle, retreatment after 6 months or with persistent IRs). The primary objective was the incidence of IRs after premedication. Secondary endpoints included sedation due to antihistamines and time to readiness for discharge. Sedation was reported by patients on a scale of 0-4 (0 = none to 4 = extremely severe). No formal statistical analyses were planned given the exploratory nature of the study. Results: Adults primarily with cancer (n = 31 [91%]) were enrolled during the COVID-19 pandemic, from March 25 to November 23, 2020. The median age was 65 and 67 years in the IV cetirizine and diphenhydramine groups, respectively. The number of patients with IRs was 2/17 (11.8%) with IV cetirizine versus 3/17 (17.6%) with IV diphenhydramine. The mean sedation score in the IV cetirizine group compared to the IV diphenhydramine group was lower at all time points, including at discharge (0.1 vs 0.4, respectively). Mean time to discharge was 24 minutes less with IV cetirizine (4.3 hours [1.5]) versus IV diphenhydramine (4.7 hours [1.2]). This difference was greater (30 minutes less) in those ≥65 years of age (4.4 [1.3] vs 4.9 [1.0] hours). Regardless of whether patients received paclitaxel (n = 9) or an anti-CD20 (n = 25), patients had less chair time when premedicated with IV cetirizine. There were fewer treatment-related adverse events (AEs) with IV cetirizine (2 events) than with IV diphenhydramine (4 events). Conclusions: This was the first randomized, controlled trial evaluating IV antihistamine premedication for IRs and chair time. It was shown that IV cetirizine can prevent IRs, with less sedation, fewer related AEs and reduced chair time compared to IV diphenhydramine. This improves infusion center operations and patient experience. Clinical trial information: NCT04189588.
Oncology consults in admitted cancer patients: The ways to reduce length of stay.
Authors: Baralo Bohdan , Hanif Muhammad , Krupadev Archen , Iqbal Sabah , Kagita Navyamani , Mustaqeem Ruqqiya , Patel Neel S , Panda Monisha , Choi Eugene Jinkyu , Thirumaran Rajesh
Published: June 2021

e13516

Background: The cancer patients, while being admitted to the hospital often have an oncologist consult (OC) through the admission. The goal of the study is to assess, whether OC impact the length of stay (LOS) and to define the group of cancer patients in whom omitting the OC can decrease LOS. Methods: We reviewed 415 admissions of cancer patients from 1/1/2018 to 11/30/2020 to the both campuses of Mercy Catholic Medical Center. We included patients who are 18 years or older with confirmed malignancy. We excluded COVID positive, patients who died during admission, were transferred to tertiary care institutions, or were recommended hospice care, but decided to continue treatment despite poor prognosis. Patient with hematologic disorders were excluded as well. The LOS of stay in cancer patients with and without OC will be compared using two tailed unpaired t-test and Mann-Whitney test ( < 20 admissions in each group, or one of the groups had a largely skewed data). Sub-analysis will be done accounting for Charlson score, spread of the disease and reason of admission (cancer vs non-cancer related). Statistical software Prism 9 will be used for analysis. Results: 290 admissions were selected using inclusion and exclusion criteria. Throughout all admission 234 admission had OC and mean LOS was 4.86 day compare to 4.23 in 56 patients, who did not have OC. Patients with non-cancer related (non-CR) admissions who had Charlson score ≤6 and no OC had shorter LOS (13 admission with median LOS 3 days) compared to those who had OC (11 admissions with LOS 7days), p 0.0462. Also, patient with non-CR admission and localized cancer tend have shorter LOS when no OC involved (15 admission with median LOS 6 days) compare to OC (16 admissions with median LOS 2.5 days), p 0.0365. No other significant difference in LOS were observed (Table). Conclusions: The cancer patients admitted for the reasons not related to their primary malignancy and who have either localized disease or Charlson score < 6 have shorter length of stay when OC not done. The limitation of the current study is the small number of patients in analysis subgroups, as well as fact that patients who had OC may have more severe disease during admission, despite the fact that patient had same extend of disease and comorbidities. Study with larger number of admissions may be necessary to confirm findings of this study.[Table: see text]
The impact of COVID-19 pandemic on oncology workload: The experience of an Italian Reference Cancer Center.
Authors: Corvaja Carla , Targato Giada , Garattini Silvio Ken , Barazzutti Cristina , Bin Alessandra , Donato Raffaela , Mansutti Mauro , Riosa Chiara , Rizzato Simona , Troiero Graziella , Fasola Gianpiero
Published: June 2021

e13520

Background: Since its outbreak in January 2020, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic dramatically affected health systems worldwide and a prompt realignment of clinical activities had to be thought. International Oncology guidelines recommended that routine oncology care continued to be delivered, ensuring triage procedures to prevent COVID-19 diffusion alongside treatments prioritization. Aim of this study was to assess the variation of activity volumes due to COVID-19 pandemic in the Oncology Department of the Academic Reference Cancer Center of Udine, Italy. Methods: We extracted activity volumes from the electronic “Data Warehouse” accountability system and compared activity in 2020 with historical activity in 2019. We then narrowed the analysis to the peak of COVID-19 pandemic, comparing data of a four-months period (February-May 2020 vs 2019). In accordance with the Italian Association of Medical Oncology guidelines, the activities analyzed included: new patients referrals, first consultations, new therapy assignments, treatment prescriptions and therapy administrations, disease re-assessments, follow-up visits, tele-examinations, unplanned visits and ward discharges. Results: Overall, throughout COVID-19 pandemic a negligible reduction in the number of first consultations (-5%) and new patients referrals to our Oncology Department (-10%) was detected. Of note, a significant reduction in the number of unplanned oncologic visits was observed (-23%). The replacement of follow up visits with telephonic interviews with the interpretation of laboratory and radiologic examinations (tele-examinations) led to a substantial reduction in follow-up visits throughout 2020 (-25%). Conversely, treatment-related activities, including new therapy assignments (+1%), treatment prescriptions and therapy administrations (+2% and +3%, respectively), confirmed the increasing trend of the previous year. Interestingly, similar trends were observed in the four-months peak period with a substantially higher decrease in follow-up visits in 2020 vs 2019 (-51%), whereas treatment-related activities remained stable. Conclusions: In the context of COVID-19 pandemic, our Oncology Department maintained stable performances on critical oncology activities. Strict triage procedures, serial swabs for patients and healthcare professionals and strategic follow-up visits remodulation were crucial. Notwithstanding the significant decrease in cancer treatments observed in several published reports, our experience demonstrates that the reorganization of oncology departments during a global pandemic is feasible and it should be pursued to preserve patients’ safety without compromising the continuum of care.
Determining the cancer diagnostic interval using administrative data in a cohort of patients with pancreatic ductal adenocarcinoma (PDAC).
Authors: Paterson Bailey , Kong Shiying , Mahar Alyson , Webber Colleen , Lee-Ying Richard M. , Cheung Winson Y. , Groome Patti , Karim Safiya
Published: June 2021

e13551

Background: PDAC is a leading cause of cancer death that is often diagnosed at an advanced stage. Population-based administrative data can be a valuable resource for studying the diagnostic interval, defined as the time from the first related healthcare encounter to cancer diagnosis. The objective of this study was to determine the diagnostic interval in a cohort of patients with PDAC using an empirical approach. Methods: This is a retrospective, cohort study of patients diagnosed with PDAC from 2007 – 2015 in Alberta, Canada. We used the Alberta Cancer Registry, physician billing claims, hospital discharge and emergency room visits to identify and categorize cancer-related healthcare encounters before diagnosis. We used statistical control charts to define the lookback period for each encounter category and used these lookback periods to identify the earliest encounter that represented the start of the diagnostic interval (index contact date). The end of the interval was the diagnosis date. Quantile regression was used to determine factors associated with the diagnostic interval. Results: We identified 3,142 patients with PDAC. Median age of diagnosis was 71 (IQR 61-80). We identified an index contact date and thus a diagnostic interval in 96.5% of patients. The median diagnostic interval length was 76 days (IQR 21-191; 90th percentile 276 days). A higher Elixhauser comorbidity score (+18.57 days/ 1 point increase, 95% CI 16.07-21.07, p<0.001) and stage 3 disease compared to stage 2 disease (+22.55 days, 95% CI 5.02-40.08, p=0.01) were associated with a longer diagnostic interval. Conclusions: In this cohort of patients with PDAC, there was a wide range in the diagnostic interval with 10% of patients having a diagnostic interval of approximately 9 months. Diagnostic interval research using administrative databases can understand variations in diagnosis times and can inform early detection efforts by identifying where and in whom delays may occur.
Improving consent forms for first-in-human trials through participant feedback.
Authors: Sibold Hannah Claire , Campbell Gavin Paul , Bourgeois John , Dixon Margie D. , Harvey R Donald , Pentz Rebecca D.
Published: June 2021

e13563

Background: Risks and benefits of investigational agents that have not been tested in humans are, at best, incompletely characterized in nonclinical investigations. Despite the growing emphasis to include patient voices in clinical trial design, no published research has explored patient preferences on how best to convey the information that the agent has not been tested in humans. This study established that First in Human (FIH) consent forms present this information in different locations and queried participants for their input on the preferable FIH consent form structure. Methods: Consent forms for FIH oncology trials open to accrual at Winship Cancer Institute in 2019-2020 were analyzed for (1) the location of the mention that the study drug has not been used in humans before (FIH information), (2) the location of animal and other nonclinical data, and (3) placement of the risks section. Patients offered enrollment in a FIH trial were eligible for this study. Participants were interviewed during a clinic visit after consent was obtained. An ethics researcher asked questions about the participant’s opinions on the wording and placement of the FIH, nonclinical, and risk information in the specific trial consent form. All interviews were audio-recorded and double coded by two independent coders. The location of FIH and nonclinical data in the consent forms was compared to the patient’s suggested location for this information. Results: Saturation of themes was reached after interviewing 17 (17/19, 89% accrual) participants who were enrolled in 9 different FIH trials. Twenty FIH consents were qualitatively analyzed. Preferred placement compared to actual consent placement is listed in the table. 82% (14/17) of participants thought that nonclinical data on risks and efficacy was important to mention. 95% (19/20) of consents listed nonclinical data and most participants thought the placement in the consent was appropriate but 18% (3/17) of participants wanted the information earlier in the consent. No consent forms that were analyzed had the risks section before the study schedule; however, 47% (8/17) of participants wanted to move the risks sections before the study schedule. Conclusions: There is considerable variation in the layout of FIH consent forms that does not align with patient preferences. Standardization of FIH consent forms to better reflect patient input is essential in order to promote understandability of these important yet sometimes misunderstood clinical trials and to ensure ethical informed consent.[Table: see text]
The Neat-HER virtual registry: Updated results on HER2+ breast cancer patients receiving neratinib as extended adjuvant therapy.
Authors: Vidal Gregory A. , Tripathy Debu , Hill Nina , Lalla Deepa , Hanson Gillian , Drozd Daniel R. , Xu Feng , Rugo Hope S.
Published: June 2021

e13565

Background: Data from traditional registries are usually limited to patients treated at study sites. Virtual registries can enroll a broader real-world population. Neat-HER is a U.S.-based virtual registry pilot through PicnicHealth that is enrolling patients with HER2+ breast cancer receiving neratinib as extended adjuvant therapy. Methods: Neat-HER evaluates the feasibility of enrolling patients and answering research questions using a novel electronic platform. Eligibility includes receipt of neratinib in the extended adjuvant setting, signed informed consent for medical record retrieval/data abstraction and age > 18 years. Patients who do not complete enrollment procedures, are participating in a clinical trial or have metastatic disease are excluded. Patients are recruited through multiple mechanisms including private social media groups, treating clinicians and patients enrolled in the Puma Texting Program. Patient health records for breast cancer-related treatment are collected from time of diagnosis to 1-year post-enrollment in the registry. Research questions focus on patient and tumor characteristics, receipt of therapy (e.g. radiotherapy, adjuvant therapy), neratinib duration, and diarrhea prophylaxis. Results: 33 patients with HER2+ early-stage breast cancer who received neratinib as extended adjuvant therapy have been enrolled in this registry study since December 2018. Median age was 50 years, with 79% of patients self-identifying as white. 82% of patients had hormone receptor-positive (ER/PR) disease and 73% of patients had node-positive disease. Prior HER2-targeted adjuvant therapy regimens were as follows: trastuzumab with paclitaxel (9%); trastuzumab/pertuzumab in combination with a taxane(s) (91%). 17 patients (52%) completed 12 months of neratinib treatment; 4 patients (12%) discontinued treatment early; 10 patients (30%) were still ongoing at the time of data cutoff. 31 patients (94%) had diarrhea prophylaxis discussed prior to the start of neratinib treatment. Conclusions: Neat-HER provides useful information on patient/tumor characteristics and treatment patterns in a real-world cohort receiving extended adjuvant neratinib and patient recruitment is ongoing. Updated results show that this pilot virtual registry continues to be a feasible and efficient modality to collect important data on descriptive characteristics and treatment patterns for a patient population derived from real-world practice settings. Validation of this method is needed and could be used in other tumor types.
Use of single-arm trials to support malignant hematology and oncology drug and biologic approvals: A 20-year FDA experience.
Authors: Agrawal Sundeep , Arora Shaily , Vallejo Jonathon Joseph , Gwise Thomas , Chuk Meredith Kathleen , Amiri-Kordestani Laleh , Pazdur Richard , Kluetz Paul Gustav , Beaver Julia A.
Published: June 2021

e13572

Background: Improved understanding of the underlying biology of cancer has led to a paradigm shift in cancer drug development and has paved the way for many products to receive accelerated or regular approval based on non-randomized/single arm trials (SATs). Given the high unmet medical need of cancer patients, challenges with lengthy and confounded survival endpoints, and difficulty enrolling rare biomarker-defined subsets of disease, SATs have been used to evaluate a variety of cancer therapies. Unlike time to event endpoints, the objective and clinically relevant endpoint of response rate (RR) and duration of response is interpretable in SATs, as spontaneous tumor shrinkage is not expected. Methods: A search of FDA databases identified all drugs and biologics approved for malignant hematology and oncology indications from January 1, 2001, to December 31, 2020 based on SATs. Data sources included approval letters, U.S. prescribing information, and clinical review documents. The definition of response varied by setting and time period (e.g. RECIST, WHO, IWG, etc.). Results: Between January 1, 2001 and December 31, 2020, FDA granted 153 new indications based on SATs, including 102 accelerated approvals (AAs) and 51 regular approvals (RAs). Overall, 69 approvals (45%) were for new molecular entities and 84 (55%) were expanded indications. Response rate was the most common endpoint used in the trial providing substantial evidence of efficacy to support approval [120/153, (78%)]. The durability of response was also considered to support evidence of clinical benefit. Of the 102 AAs, 38 (37%) have fulfilled their post-marketing requirement (PMR) to verify clinical benefit, 59 (58%) are pending verification of benefit, and 5 (5%) have been withdrawn from the market. Of note, 88% (52/59) of AAs pending verification of benefit occurred in the last 5 years alone (22 AAs in 2020, 8 in 2019, 8 in 2018, 12 in 2017, and 2 in 2016). Between 2001-2020, 58 (38%) new indications were granted for kinase inhibitors, 34 (22%) for immune checkpoint inhibitors (CPIs), and 61 (40%) for drugs with other mechanisms of action including but not limited to antibody-drug conjugates, cytotoxic drugs, and non-CPI monoclonal antibodies. Conclusions: In the last two decades, SATs have been effectively used to study anti-cancer therapies in well-defined patient populations using durable RR as an objective and interpretable clinical endpoint. Although randomized clinical trials remain the gold standard in clinical research, SATs have allowed for rapid advancements in oncology drug development and will continue to serve an important role in bringing new therapies to patients with unmet need.
Expedited development and review pathways for novel oncology drugs.
Authors: Vadola Lisa Ambrosini , Winter-Vann Ann , Knoll Miriam , Whitsell Robin
Published: June 2021

e13578

Background: Following approval of the Food and Drug Administration (FDA) Safety and Innovation Act in 2012, the FDA launched a 3-year plan to promote innovation, increase stakeholder involvement, secure the drug supply chain, and fund these endeavors by collecting user fees. The FDA created its fourth expedited pathway, Breakthrough Therapy Designation (BTD) to focus on the development and approval of therapies to treat serious and life-threatening conditions that lack adequate therapies. Our 2017 study (ASCO abstract #e18270) identified a trend of increased use of these approaches with oncology drugs, particularly the BTD, which was a nascent pathway at the time. We aimed to reexamine FDA pathway and approval trends in oncology interventions. Methods: We analyzed publicly available data on novel drug approvals by the FDA’s Center for Drug Evaluation and Research (CDER) from 2012-2020 and the 4 expedited pathways (BTD, Accelerated Approval, Fast Track Designation [FTD], and Priority Review). Results: Between 2012 and 2020, CDER approved 380 new chemical entities, including 101 oncology drugs. Due to data limitations, 3 novel oncology biologics (approved by the Center for Biologics Evaluation and Research) and 4 diagnostics were excluded from the analyses. Oncology drugs comprised a mean 27% (range 14-34%) of all approvals from 2012-2020, including 25% from 2012–2016 and 28% from 2017-2020. Of all approved oncology drugs from 2012-2020, 94% (range 82-100%) utilized at least one expedited pathway. Oncology approvals were more likely than non-oncology approvals to have used one or more expedited pathways. Use of these pathways for oncology approvals increased from 2012-2016 to 2017-2020: ≥2 (65% vs 78%) and ≥3 (35% vs 50%) pathways. BTD usage for oncology drugs increased from 35% in 2012-2016 to 57% in 2017-2020, though for 2012-2016, the time interval between awarding the (new) designation and the remainder of development activities must be considered. Presumably because BTD grants additional benefits over FTD, generally the use of FTD for oncology drugs has declined over time. The use of Priority Review and Accelerated Approval has remained the same. Despite the pandemic, for oncology and non-oncology drugs alike, approvals using pathways remained consistent between 2019 and 2020. Conclusions: Efficient FDA review plays an important role in oncology drug development. Since its inception in 2012, BTD has been adopted and expeditiously used, comprising more than half of all novel oncology drug approvals from 2017-2020. Our data show a gradual increase in approvals of drugs granted BTD, which, given the duration of drug development, likely reflects the time between the acceptance of the BTD request and remainder of the pre-submission development activities. As BTD was expressly developed to increase stakeholder interaction and prioritize innovation, the speed-to-adoption and use of this pathway among oncology interventions is promising.
MLkit: A machine-learning-powered automatic workflow for classification of cancer samples.
Authors: Li Qingyuan , He Ji
Published: June 2021

e13583

Background: In the era of data explosion, precision classification of cancer samples based on multi-dimensional medical data provides more insights into disease mechanism and useful hints on clinical treatment associated with tissue of origin, recurrence tendency and prognostic of chemotherapy or immunotherapy. We developed an automatic workflow MLkit to select features from large-scale multi-dimensional medical data and conduct classification through various machine learning techniques. Methods: MLkit is an automatic and one-stop workflow for classification of cancer samples with four modules: preprocessing (missing data remove or imputation and feature standardization), feature selection (unsupervised multi-statistics and supervised multiple machine estimators with recursive feature elimination and cross-validation), modeling (hyper-parameter, performance evaluation and probability calibration) and prediction. Most of current machine learning algorithms were implemented in this workflow, including linear model (logistic regression, ridge regression and stochastic gradient descent), ensemble model (gradient boosting, random forest, xgboost, catboost, lightgmb and stacking), support vector kernel (linear and non-linear), naive Bayes, k-nearest neighbors and multi-layer perceptron neural network. To evaluate the performance of this workflow, we utilized it to fit a model used for prediction of tissue of origin based on 450K DNA methylation data of 2,210 samples from lung, kidney and breast cancer patients collected in TCGA. Results: MLkit performed well in the prediction of tissue of origin for independent validation sets of cancer patients with stable feature selection, automatic hyper-parameters and efficient probability calibration, in which the model achieved AUCs ranged from 0.85 to 0.96. In addition, we also utilized this workflow on extensive real world data and most of results showed superior accuracy and stable performance. Conclusions: MLkit facilitates automated and one-stop classification of cancer samples using machine learning algorithms. It can be operated with simple command line, making it accessible to a broad range of users. The well performance of this workflow based on multi-dimensional medical data can help to improve the discovery of tumor biomarker and optimize clinical follow-up and therapeutic treatment for cancer patients.
Electronic patient reports outcomes and symptom monitoring for hematopoietic stem cell transplantation: A PILOT study.
Authors: Jorge Thiago William Carnier , Scheinberg Phillip , Campagnaro Melina , Filho César , Cartolano Lorenzo , Singh Jean , dos Prazeres Luiz Felipe , Mota Camila , Teodoro Juliana , Delijaicov Dimitra
Published: June 2021

e13592

Background: Patients undergoing hematopoietic stem cell transplantation (HSCT) present with various symptoms during hospitalization. The daily life routines of those undergoing HSCT change significantly before, during, and after the transplant. The utilization of technologies of digital support for oncological patients through mobile applications is a trend. WeCancer App is an electronic patient-reported outcome tool that provides on-demand multidisciplinary digital support by nurses, psychologists, and nutritionists. It also encompasses real-time remote patient monitoring, a notification center to the patient and medical staff, symptom monitoring, medication control, and a content hub with reliable medical information. Methods: This study examined whether electronic patient-reported outcomes [e-PROs]) in post-HSCT patients (6 patients included) up to 16 weeks after hospital discharge. The following were observed: number of symptoms reported, specific symptoms, toxicity after transplantation, application adherence, number of accesses, chat interactions, total hours of chat time. Patients could report common symptoms through a mobile application, for monitoring, symptom management, and follow-up with a specialized nurse, determining care based on digital support clinical protocols through online chat. The alerts made through the chat system guided the nursing team's clinical actions about online clinical management that can stratify the risk by crossing the intensity of symptoms by the ESAS scale (Manchester classification) and promoting preventive educational conduct of vigilance and risk mitigation. Results: Median follow-up for overall treatment was 16 weeks. The e-PRO completion rates were > 90% at baseline and ≥ 80% at all on-treatment assessments and adherence. In-App adherence 329 reports were made 218 (66.26%) symptoms, 66 (20.06%) wellness, 30 (9.11%) gratitude and 15 (4.6%) exercise. Of the 64 chat interactions, there were 19.25 total hours and 18.05 average minutes per patient. The chat questions and interactions reported were: 48.2% symptoms, 27.7% treatment questions, 9.6% exams, 7.2% emotional aspect, 6% nutritional aspect and 1.3% medical devices. Some monitored patients (2) had guidance on outpatient graft versus host disease (GvHD) early in its onset with success avoiding a visit to the office or emergency room. Conclusions: We show the real-life benefits of incorporating ePRO into a post HSCT strategy adjunct to the treatment center. Symptoms that would only be brought to the physician in the next appointment were communicated in real-time to the transplant team, permitting early intervention and likely to reduce transplant-related deterioration and later interventions. The results suggest that further research should be done to prove the effectiveness of the App.
Impact of the COVID-19 pandemic on clinical activity during the lockdown in North France: A single center experience.
Authors: Hammoudi Ali , Marliot Guillaume , Cucchi Margot , Mahi Naima , Pannier Diane , Leblanc Eric , Mirabel Xavier , Ceugnart Luc , Robin Yves-Marie , Lartigau Eric , Penel Nicolas
Published: June 2021

e13594

Background: During the French COVID-19 pandemic, clinical activity for cancer care has declined and modified the management of patients in cancer institute. France has imposed two national lockdowns of the population (from March 17 to May 11 and from October 30 to December 15 2020). We evaluate the impact of the lockdown period in North France on clinical activity. Methods: We measured and compared key-indicators of clinical activity between different periods: 2019 versus 2020; before and during the first and second lockdown. Results are given as percentage of changes with 95% confidence interval (CI). Results: The comparative analysis between 2019 and 2020 showed that most clinical activities except hospitalizations (-0.0% [-0.2; +0.1%] has changed. There was a significant increase in overall treated patients (+0.4% [+0.3; +0.5], telemedicine +99.9% [+99.4; +99.7], MRI (+8.8% [+8.2; +9.5], ambulatory chemotherapy (+3.5% [+3.3; +3.8]), number of chemotherapies prepared (+2.0 [+.1.9; +2.2]) and admission in palliative care unit (+15.3%, [+10.8; +19.8]). On the contrary, a significant decrease in treated patients aged > 65 years old (-6.4% [-6.9; -5.9]), incidence rate (-3.1% [-3.6; -2.7]), multidisciplinary team meeting on patient assessment (-3.1% [-3.5;-2.5]), pathology reports (-2.9% (-3.3;-2.6]), radiotherapy (-4.6% [-4.7;-4.4]) and surgery (-6.7% [-7.4;-5.6]) were observed. In 2020, before and during the first lockdown all key-indicators declined except telemedicine (+40,400%) and admission in palliative care unit (+35.5% [+31.0-+49.7]). During the first lockdown, key-indicators decreased from -63.0% [-70.3-59.2] for outpatient visits to -5.1% [-7.0-3.8] for chemotherapy. The impact caused by the second lockdown was non-significant compared to the first one since all key-indicators has increased during the second lockdown: from +23.8% [+22.2; +25.5] for radiotherapy to +76.6% [+72.5; +79.5] for the management of new cases. Conclusions: Dramatic changes occurred in 2020 during the COVID-19-related lockdown compared to 2019. An Increase in chemotherapy treatment and admission on palliative care unit and a decrease in surgery and radiotherapy strongly suggests that the clinical activity was changed in 2020 compared to 2019. This was in line with the reduction of cancer screening in 2020. The impact of the first lockdown on clinical activities was higher compared to the second one. These observations should be investigated further in order to better understand the effects of a pandemic-related lockdown on cancer care.
National survey on access to new oncology drugs pending health technology assessment and financial arrangements.
Authors: van Waalwijk van Doorn-Khosrovani Sahar Barjesteh , Pisters-van Roy Anke , Bloemendal Haiko , Gelderblom Hans
Published: June 2021

e13599

Background: In the Netherlands, the health insurance package usually covers cancer drugs after EMA approval and positive recommendation of the Dutch Society of Medical Oncology (NVMO). However, the government can temporarily exclude newly licensed indications with high budget impact from coverage until the national HTA-body advises on the clinical effectiveness and cost effectiveness. Based on the recommendations of the HTA-body, the government negotiates a financial arrangement with manufacturers. Because submitting value dossiers, assessments and negotiations takes time there have been concerns regarding patients’ access to these novel treatments, especially for life threatening conditions such as cancer. Due to a lack of transparency, it is not known to what extent patients are given access to ‘free of charge programmes’ (FCPs). Methods: A list of oncology drugs and indications which were temporarily excluded from reimbursement due to negotiations with the government (July 2015-Dec. 2020). We contacted all the pharmaceutical companies that were engaged in the process above, to inquire about access to their products during the HTA evaluation and negotiations. Results: In total 17 oncology drugs (46 EMA registered indications) of 11 companies were subjected to financial agreements by the government. In 41,3% (19/46) of cases, FCPs were available via individual prescriber requests in a selected number of hospitals. In all other cases such arrangements were not needed because alternative treatment options were available (15,2%; 7/46) or because treatment was not recommended by the NVMO (13,0%; 6/46). For one indication FCP was available but the treatment eventually received a negative recommendation. In 30,4% (14/46) of the cases there was immediate reimbursement in place following a positive NVMO recommendation through umbrella agreements. Such agreements cover existing indications but also all the indications that will be licensed in the future. Umbrella agreements were especially set up for immune checkpoint inhibitors that showed benefit across multiple indications. As anticipated, some patient-access programmes had already started prior to EMA approval. In 5 cases an official compassionate use programme was set up through the Dutch Medicines Evaluation Board prior to authorisation. Conclusions: Our survey indicates that all manufacturers are committed to enabling patients’ and clinicians’ early access to their products pending payers’ approval in a high income country such as the Netherlands. However, the lack of transparency regarding the hospitals offering these programmes may result in inequity in access. Besides, there is no structural data collection. Recently, the NVMO has established a platform (DRUG Access Protocol) to harmonise all compassionate use programmes and FCPs, generating real-world data and ensuring equal access for all patients.
Preclinical evaluation of novel CDK4/6 inhibitor GLR2007 in glioblastoma models.
Authors: Yin Lei , Yao Zhenglin , Wang Yue , Huang Julius , Mazuranic Michelle , Yin Ang
Published: June 2021

e14023

Background: Glioblastoma multiforme (GBM) is characterized by a high frequency of cyclin-dependent kinase (CDK)4 and CDK6 pathway dysregulation. CDK4/6 inhibitors palbociclib and abemaciclib are approved for the treatment of breast cancer, but poor blood–brain barrier (BBB) penetration limits their efficacy in GBM. GLR2007 is a novel CDK4/6 inhibitor with potential for improved penetration across the BBB. Here, we report on the activity of GLR2007 in GBM cell lines and its anti-tumor efficacy in mouse xenograft models. Methods: Three in vitro assays were used to assess the activity of GLR2007. Inhibition of CDK4/6 enzymatic activity by GLR2007 or palbociclib was calculated, and cell cycle stages were analyzed in U87-MG cells treated with vehicle control or GLR2007 for 24 h. Cell viability was evaluated in U87-MG and U118-MG cell lines after culture for 72 h with GLR2007 or abemaciclib. In vivo evaluation of the anti-tumor efficacy of GLR2007 versus vehicle, abemaciclib, and/or palbociclib was performed in BALB/c nude mouse GBM xenograft models. Quantitative whole-body autoradiography was used to determine the distribution of [14C]GLR2007 in the tissues of Sprague Dawley rats. Results: GLR2007 potency toward CDK4 and CDK6 was 33.1 and 3.8 times that of palbociclib, respectively. At concentrations >13.72 nM, GLR2007 caused G1 arrest of U87-MG cells. GLR2007 inhibited proliferation in U87-MG cells (IC50 15.6±2.4 nM) and U118-MG cells (IC50 23.2±5.2 nM). Anti-tumor efficacy of GLR2007 versus vehicle control was observed in two mouse GBM xenograft models (Table). Studies performed in rats demonstrated the distribution of [14C]GLR2007 in whole brain tissue following a single oral dose, with total radioactivity levels in the brain exceeding those in plasma by 2.3–4.5-fold from 2–6 h after dosing. Conclusions: These preclinical studies demonstrate the potential of GLR2007 as a novel CDK4/6 inhibitor for treatment of GBM. GLR2007 showed numerically greater anti-tumor efficacy than approved CDK4/6 inhibitors in xenograft models, and evidence of substantial central nervous system penetration. [Table: see text]
Assessment of low-intensity transcranial magnetic stimulation (TMS) in treatment for high-grade glioma (HGG).
Authors: Popov Ivan A. , Kit Oleg I. , Shikhlyarova Alla I. , Frantsiyants Elena M. , Rostorguev Eduard E. , Engibaryan Marina A. , Timoshkina Natalya N. , Gusareva Marina A. , Potemkin Dmitrii S. , Stasov Vitaliy V. , Arapova Yulia Yu. , Zhukova Galina V. , Atmachidi Dmitriy P. , Nikitin Emzari S. , Kuznetsova Natalya S. , Pandova Olga V. , Khatyushin Vladislav E.
Published: June 2021

e14027

Background: The existing modern standards of combination treatment of HGG patients do not provide recovery and a long-term favorable prognosis, and the increasong incidence of HGG determines the need for additional effective technologies for anticancer and decongestant therapy. One of such methods involves TMS, and we have reported its preliminary assessment earlier (DOI: 10.1200/JCO.2020.38.15_suppl.2545). In this study, we continued the observation to examine the survival of patients. Methods: Patients with HGG received combination treatment: stage 1 – surgical removal of tumors within visible unaltered tissues; stage 2 – radiation therapy (the Varian Novalis linear accelerator) to the bed of the removed tumor, single boost dose 2 Gy, total boost dose 60 Gy; stage 3 – multi-course chemotherapy: temozolomide 150 mg/m² on days 1-5 with a 23-day interval. Starting from the second day after surgery, patients of group 1 (n = 25) received 10 TMS sessions, and during radiotherapy – 15 TMS sessions. Patients of group 2 (n = 25) received combination treatment without TMS. 6 and 12 months after the surgery, survival of patients was assessed with the Kaplan-Meier method and the Log-Rank test. Results: After 6 months of the follow-up, the survival of patients in group 1 remained at 100%, while in the control group it decreased to 88.8±8.7%. The difference in the 1-year overall survival was even more pronounced: in group 1, it was 68.5±10.4%, exceeding the value in group 2 (52.0±7.5%.) The differences were statistically significant (Log-Rank test p = 0.001). Conclusions: The results confirm the effectiveness of accompanying TMS in the early postoperative period, as well as at the stage of radiation therapy. The undoubted effectiveness of the considered techniques makes it expedient to include this type of treatment in the combination therapy for HGG patients. The reported study was funded by RFBR, project number № 19-315-90082\19.
Concurrent chemoradiation in the management of newly diagnosed glioblastoma multiforme: Retrospective review of single center experience over a period of 10 years.
Authors: Price Louise , Ziff Charlotte , Elmasry Abdelfattah , Giridharan Selvaraj
Published: June 2021

e14028

Background: Glioblastoma Multiforme (GBM) is the most common primary intracranial tumour of the brain. The standard of care first line management is maximum safe debulking followed by concurrent chemo radiation (Stupp et al, 2005). In spite of further recent advances, median survival still remains poor and ranges between 14 to 21 months, especially in the MGMT unmethylated group. There are no randomised trials investigating less than 6 cycles of adjuvant temozolomide (TMZ). In our study we retrospectively analyse the impact on overall survival (OS) and progression free survival (PFS) in cases where adjuvant treatment has been discontinued due to toxicity or patient’s fitness Methods: We collected data from 2007 to 2016 for a cohort of patients who underwent adjuvant treatment for GBM following histological diagnosis. The final analyses included patient’s who completed concurrent chemoradiotherapy to a dose of 60 Gray in 30 fractions and had at least one cycle of adjuvant TMZ chemotherapy Results: Of 110 patient cohorts, 57% of patients completed adjuvant chemo radiotherapy followed by 4-6 cycles of adjuvant TMZ, 43% received 3 or less cycles of TMZ. Overall PFS was 11.9 months. Those that completed 4 or more cycles of adjuvant TMZ had an improved PFS (Log rank test P-value 0.001) versus those that completed 3 or less cycles. On cox analysis the number of adjuvant cycles of TMZ significantly affects OS, P-value 0.0003. Median overall survival was 16 months for the whole group, but was 10 vs. 20 months for the two groups. On cox analysis we also identified second line chemotherapy had a significant impact on OS (cox model P-value 0.002) Conclusions: We identified patients receiving three or fewer cycles of adjuvant TMZ had poorer outcomes. Second-line chemotherapy improved outcomes at relapse regardless of redo surgery.
A first-in-human phase dose-escalation study of YH002, a recombinant humanized agonistic anti-OX40 IgG1 monoclonal antibody, in patients with advanced solid tumors.
Authors: Ganju Vinod , Cooper Adam , Wilkinson Kate , Park John J.
Published: June 2021

e14501

Background: YH002 is a recombinant humanized IgG1 antibody that targets the human OX40 receptor. Preclinical studies have demonstrated the specificity, potency, and anti-cancer efficacy of YH002 in a comprehensive panel. The totality of nonclinical data supports progression of YH002 into clinical studies in adult patients (pts) with advanced solid tumors. Methods: This is an ongoing phase 1 dose-escalation study. Patients with advanced or metastatic refractory solid tumors received YH002 as single agent by IV administration at 0.01 to12.0 mg/kg dose levels every 21 days (Q3W), to evaluate the safety, tolerability and preliminary efficacy. An accelerated titration dose escalation design followed by a traditional 3+3 dose algorithm were utilized to assess dose-limiting toxicity (DLT) and identify MTD and/or RP2D. Tumor assessments were performed per RECIST v1.1 every 9 weeks. Results: By December 31 2020, six patients were enrolled and treated at escalating dose levels of 0.01 (n=1), 0.03 (n=1), 0.1 (n=1) and 0.3mg/kg (n=3), with tumor types including colon cancer, thymic cancer, prostate cancer, colorectal cancer, breast cancer and bladder cancer. Median treatment duration was 10.2 weeks (range 2 – 18). The median age of patients was 67 years old (range 47-78). These patients had progressed after a median of 2 prior lines of available standard therapy. As of data cutoff, no dose limiting toxicities (DLTs), no Grade (G) 3 or above adverse events (AE) or AEs leading to treatment discontinuation were reported. Drug-related adverse events (AEs) were all G1/2 events and occurred in 4 patients, including 8 G1 AEs (pneumonitis, rash, pruritus, arthralgia, myalgia, fatigue, lethargy, rash pruritic) and 3 G2 AEs (1 pneumonitis and 2 fatigue). Out of 5 patients having tumor assessment by RECIST, one pt with Thymic SCC at 0.3 mg/kg had best response of stable disease at week 9, one pt with prostate cancer at 0.1 mg/kg experienced Non-CR/Non-PD, and rest of 3 pts experienced progressive disease. Conclusions: These preliminary results demonstrate that YH002 was safe and tolerable up to 0.3mg/kg. Updated safety and antitumor activity will be presented. Clinical trial information: NCT04353102.