bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of palbociclib in treatment of HR-positive advanced breast cancer patients: A single center real-world experience.
Authors: Vaid Ashok K. , Sharma Devender , Wadhwa Jyoti , Sharma Nagender , Mishra Saurabh , Gautam Dheeraj , Sen Ashok , Raju Anisha , Yadav Lavina , Verma Girdhar 
Published: June 2022

e13035 Background: With an estimated 2.3 million new cases (11.7% of all cases), female breast cancer is the leading cause of cancer globally as of 2020. Metastatic or advanced breast cancer is an incurable disease with a 5-year overall survival rate of 28.1%. Palbociclib, a cyclin-dependent kinase 4/6 inhibitor combined with an aromatase inhibitor, is approved to treat HR+/HER2- metastatic breast cancer (MBC). The present single-arm study evaluates the real world experience of efficacy and safety of Palbociclib-Letrozole for the treatment of HR+/HER2- MBC in the Indian population. Methods: MBC patients with or without prior chemotherapy and hormone therapy were treated with Palbociclib 125 mg once daily (3/1 schedule) plus Letrozole 2.5 mg once daily. The efficacy was recorded as objective response or disease control rate based on the response as per the RECIST criteria. The study also reports the incidence and severity of adverse events during the treatment duration. The tolerability was assessed per Common Terminology Criteria for Adverse Events (CTCAE) v.4.0 and coded using Medical Dictionary for Regulatory Activities (MedDRA) v.21.0. Results: A total of 102 patients were treated from 2017 to 2020 at the tertiary cancer center. The efficacy response is captured as per the investigator's assessment of the disease response. The response is as captured for 100/102 patients (two patients lost to follow-up) and are represented in Table. About 17% (23/100) patients achieved an objective response, while 54% (57/100) showed disease control. The tolerability was assessed as treatment-related side-effects (adverse events (AEs) and severe adverse events (SAEs)) as reported by the treating oncologist. Overall, 61 adverse events were observed in 40/102 (39.22%). The most-reported AE, neutropenia, was reported in 13 patients, followed by chest pain and breathlessness. Conclusions: In the present study, Palbociclib + Letrozole reported good clinical response at the end of treatment duration with a manageable tolerability profile in the Indian population.
Prophylactic use of metformin in patients on alpelisib treatment.
Authors: Filonenko Daria , Zhukova Lyudmila 
Published: June 2022

e13040 Background: Alpelisib-induced hyperglycemia (HG) is the most common adverse event leading to interruption, reduction or withdrawal of the treatment. HG is an on-target effect that depends on the baseline metabolic status of the patient. In SOLAR-1 90,6% patients with high-risk at baseline HG G3/G4 was reported. Prophylactic use of metformin may prevent HG in patients at risk. Methods: HR+ HER2-negative advanced breast cancer patients were stratified to low-, moderate- or high-risk groups of HG based on the algorithm published in [1] before starting alpelisib 300 mg + fulvestrant (Alp + Fulv). Moderate- and high-risk patients used prophylactic metformin at 500-1000 mg or 2000 mg BID with breakfast and dinner (Table). Metformin was started at least one-week prior Alp administration. Fasting plasma glucose (FPG) was monitored qw and bw in low- and moderate-risk patients, and daily with home glucometer in addition to bw FPG for high-risk patients. The primary endpoint of retrospective analysis was to assess the incidence of HG G3/G4 in different risk groups based on CTCAE V4.03 guidelines. Results: A cohort of 18 patients (median lines of previous treatment in advanced disease was five, all patients has received CDK4/6 inhibitors) treated with Alp+Fulv in the Loginov Moscow Clinical Scientific Centerin 2020-2021 included 7 low-, 3 moderate- and 8 high-risk patients. Any grade HG was reported in 13 out of 18 pts; no cases of HG G2 or G4 were detected. HG G3 was reported in 5 out of 18 patients including in 2 out of 3 moderate-risk patients, and in 3 out of 8 high-risk patients. Anti-HG drugs used included metformin (6/18); empagliflozin (4/18), and linagliptin (1/18); 1 patient required Alp dose reduction to 250 mg due to HG G3; none discontinued Alp due to AEs. Other AEs included rash (7/18; no grade 4; grade 3 in 4/18), and blood creatinine increase (8/18 – all grade 1-2).The median PFS on treatment with Alp+Fulv was 7 months. Conclusions: Prophylactic use of metformin in patients with high risk of hyperglycemia could markedly reduce frequency and severity of hyperglycemia on alpelisib.[Table: see text]
Eribulin combined with anlotinib for patients with HER2-negative metastatic breast cancer: A single-arm, multicenter, phase II study.
Authors: Yin Yongmei , Wu Xinyu , Hua Yijia , Sun Chunxiao , Liang Yan , Yang Fan , Huang Xiang , Li Wei 
Published: June 2022

e13051 Background: The group of HER2-negative accounts for 70-80% of breast cancer and effective treatments for heavily pretreated patients with HER2-negative metastatic breast cancer are urgently needed. Eribulin mesylate is a non-taxane microtubule dynamics inhibitor with a distinct mode of action which can be used as a chemotherapeutic agent for HER2-negative breast cancer after failure of anthracycline and taxanes treatments. Anlotinib is a novel multitarget tyrosine kinase inhibitor targeting VEGFR, PDGFR, FGFR, and c-Kit. This study aimed to evaluate the efficacy and safety of combined treatment with eribulin and anlotinib in patients with HER2-negative metastatic breast cancer (NCT04624711). Methods: This open-label, single-arm, phase II study enrolled females with HER2-neagtive breast cancer who underwent ≥1 line chemotherapy, including anthracyclines and taxanes, for metastatic breast cancer. Patients with hormone receptor positive breast cancer have underwent ≥1 line endocrine therapy. All patients were treated with Eribulin mesylate (1.4mg/m2, administered intravenously on Days 1 and 8 of each 21 day cycle) and anlotinib (12mg, qd, administered orally on Days 1-14 of each 21 day cycle). The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: From November 2020 to February 2022, 25 patients were enrolled in this study. Median follow-up was 3.45 months (95% CI 3.16-5.06). Median PFS was 4.6 months (95% CI 3.55-5.65). Of all the patients whose efficacy could be evaluated (21/25), no patient achieved complete response (CR); 9 (40.91%) and 10 (45.45%) patients got partial response (PR) and stable disease (SD), respectively. ORR was 40.91% and DCR was 86.36%. OS has not reached. The major treatment-related adverse events (incidence≥10%) were neutropenia(48.00%), anemia(37.93%), platelet count decreased (34.48%), fatigue (31.03%), hypoalbuminemia (20.69%), constipation (13.79%), elevated lactate dehydrogenase(13.79%), lymphocyte count decreased (10.34%) and hypertriglyceridemia (10.34%). The most common grade 3/4 adverse events were neutropenia (20.00%). 16.00% (4/25) of patients had dose reductions. Conclusions: The combination of eribulin and anlotinib showed a better treatment response and tolerable toxicity in HER2-negative metastatic breast cancer patients. Further studies enrolling more patients are still needed. Clinical trial information: NCT04624711.
Survival outcomes in patients with metastatic breast cancer treated with eribulin: A real-world evidence study from India.
Authors: Vaid Ashok K. , Wadhwa Jyoti , Sharma Nagender , Sharma Devender , Sen Ashok , Gautam Dheeraj 
Published: June 2022

e13053 Background: Eribulin is a novel synthetic analogue of halichondrin B, which acts as a microtubule inhibitor by interacting with the microtubules and inhibits the G2-M growth phase. Eribulin was approved for metastatic breast cancer (MBC) based on landmark EMBRACE (phase-3) trial, although only a small number of Asian subgroups of the population were included, and data in the Indian subset of patients is limited. Therefore, in this real-world study we retrospectively assessed the clinical outcomes of eribulin in Indian women with metastatic breast cancer (heavily pre-treated). Methods: Adult MBC patients who had advanced following at least two chemotherapy lines, including anthracyclines and taxanes, in either an adjuvant or metastatic setting and were treated with eribulin over several lines were retrospectively analyzed. Records pertaining to socio-demographics, clinical, pathology, imaging, and therapy were reviewed. The overall survival (OS), progression-free survival (PFS), and tumor response were calculated. Results: A total of 80 patients were included. The median age of patients was 54.5 years (range: 27-82). Eribulin was majorly used as a second-line and third-line chemotherapy agent in 28 (35 percent) and 24 (30 percent) of MBC patients, respectively. In 57 evaluable patients, the best objective response rate (ORR) was 43.85 percent, while the clinical benefit rate was 59.65 percent with eribulin therapy. The median OS and PFS were 17.29 (95 percent CI: 14.31-20.27) and 11.76 (95 percent CI: 9.5-14.02) months, respectively. There was positive correlation between the number of cycles and the outcomes of survival, with patients getting more than 6 cycles having superior OS and PFS. On subgroup analysis, patients with liver metastasis had significantly (p<0.001) lower mean OS (9.42 months) and PFS (3.69 months) than other sites. Conclusions: This real-world retrospective study supports and confirms the efficacy of eribulin in Indian patients with MBC (heavily pre-treated). It should be considered in the strategy of several chemotherapy lines in MBC.
Apatinib plus etoposide as second-or higher-line treatment in recurrent or metastatic triple-negative breast cancer: A single-arm, open label, prospective, phase II clinical trial.
Authors: Cao Mengru , Lu Hailing , Yan Shi , Pang Hui , Sun Lichun , Li Chunhong , Chen Xuesong , Liu Wei , Hu Jing , Huang Jian , Xing Ying , Chen Yingqi , He Ting , Zhao Danni , Sun Yuanyuan , Zhao Lin , Liu Xiaomeng , Zhang Ningzhi , Cai Li 
Published: June 2022

e13069 Background: Due to the lack of targeted therapies, the standard of care for advanced triple-negative breast cancer (TNBC) was still chemotherapy, yet its effectiveness remains unsatisfied. Therefore, an urgent need exists to find a novel treatment option for patients with TNBC. The effect and safety profile of apatinib and etoposide have been demonstrated in several clinical trials for the treatment of late-stage TNBC respectively. In the present study, we aimed to investigate the potential effect of combination therapy of apatinib plus etoposide in recurrent or metastatic TNBC. Methods: Patients with late-stage TNBC who failed at least one line of chemotherapy were recruited in our study. Eligible patients were treated with in a 3-week cycle until disease progression or unacceptable toxicity for up to a maximum of 6 cycles. Apatinib could be declined to 250mg according to patients’ condition. Patients who completed their treatment were followed every 8 weeks and their disease progress was assessed scans according to RECIST 1.1. The primary endpoint was progress-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Safety was also evaluated. Results: From August 2018 to September 2021 a total of 40 patients were enrolled in this study. Their median age was 56-year old (range, 27-76) and had received a median of 3 (range, 2-6) previous lines chemotherapy. Until January 2022, among all eligible patients, 30 PFS events were observed. The median PFS was 6 months (95% CI, 3.77̃8.23) and the median OS was 24.53 months (95% CI, 10.23-38.83). Meanwhile, 4 patients achieved partial response, 21 patients achieved stable disease, the ORR was 10% and the DCR was 62.5% In addition, the most common adverse events were hypertension (65%), nausea (47.5%), vomiting (42.5%), and hand–foot syndrome (32.5%). The most common grade ≥ 3 adverse events were hypertension (5%) and proteinuria (5%). Conclusions: The results of the study exhibited a promising clinical effect of the combination therapy of apatinib plus etoposide and acceptable toxicity in recurrent or metastatic TNBC as second-or higher-line treatment. And more results will be updated with the progress of this clinical trial. Clinical trial information: ChiCTR1800018497.
Results of the safety run-in of gedatolisib plus talazoparib in advanced triple negative or BRCA 1/2 positive HER2 negative breast cancer.
Authors: Phadke Sneha Deepak , Yu Menggang , Miller Kathy , Shah Ami N. , Danciu Oana Cristina , Wisinski Kari Braun 
Published: June 2022

e13075 Background: Metastatic triple negative breast cancer (TNBC) is a disease subtype with a poor prognosis, though advancements have been made in the use of targeted therapies, such as poly (ADP-ribose) polymerase inhibitors (PARPi) for those with germline BRCA 1/2 mutations. Up to 2/3 of TNBC tumors have acquired defects in homologous recombination (HR) DNA repair, yet PARPi monotherapy has been ineffective in extending survival in these patients. Phosphoinositide-3-kinase (PI3K)/mTOR pathway alterations are also common, and preclinical data supports that PI3K/mTOR inhibition may disrupt normal function of the HR complex and increase dependency on PARP enzymes for HR DNA repair. Thus, combining a PI3K/mTORi with a PARPi may result in a synergistic anti-neoplastic effect. Methods: The safety run-in portion of this study evaluated the safety and preliminary efficacy of the combination of weekly IV gedatolisib (PI3K/mTORi) and continuous daily talazoparib. Germline BRCA mutations were not required. The safety run-in was designed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). A 3+3 design was utilized for dose escalation, with starting dose at level 1. Dose levels are as shown in the Table. Eligibility criteria included patients ≥ age 18 who had received 1-3 prior lines of therapy for advanced TNBC or advanced HER2-negative BC with a germline BRCA 1/2 mutation. Those with untreated CNS metastasis were excluded as were those type I diabetes or uncontrolled type II diabetes, due to the risk of hyperglycemia with gedatolisib. Results: A total of 14 female patients were enrolled on to the safety run-in phase of the trial. Median age was 53 (range 30-67). Most patients (79%) were Caucasian, 14% were African American, and 7% unknown. The most common adverse events (AEs) of any grade were fatigue, anemia, nausea, and oral mucositis. Grade 1 hyperglycemia was noted in about 1/3 of the cohort, with 1 grade 3 event. There were 3 patients who experienced grade 4 AEs, thrombocytopenia (2) and lymphopenia (1). There was 1 DLT of grade 3 neutropenia which occurred at dose level 1. The MTD of gedatolisib was 180 mg and MTD of talazoparib was 1 mg. In this preliminary cohort, 3 patients achieved PR and 5 patients achieved SD. Median duration of PR was 13.34 months and median duration of SD was 4.11 months. Of the 3 patients with a BRCA 1 or 2 mutation, 2 had a best response of PR and the other SD. Conclusions: The safety run-in indicated that this combination is safe and well tolerated with mostly grade 1-2 AEs. This combination therapy has moved into the phase II trial, with 2 cohorts. Cohort A includes BRCA-wildtype patients with TNBC and cohort 2 includes those with a BRCA mutation and HER2-negative disease. Clinical trial information: NCT03911973. [Table: see text]
Evaluating anticancer agents on 3D bioprinted organoid tumors (BOT) to reduce cost and accelerate therapeutic discovery.
Authors: Patel Zeelu H. , Charania Areesha A. , Punjani Zeenia , Patel Heli K. , Sewell-Loftin Mary Kathryn , Saleh Mansoor N. , Budhwani Karim I. 
Published: June 2022

e13500 Background: Despite recent advances in therapeutics, cancer remains the second leading cause of death worldwide. Next generation cancer models hold the promise of breaking this stranglehold. However, extracting adequate tissue for precision and personalized medicine ex vivo models can be difficult depending on tumor type and tissue site. Mechanisms to expand tissue include patient derived xenografts and patient derived organoids. The former imposes a large time window to establish while the latter is constrained in space by sizescales. Advances in 3D bioprinting have improved the ability to reproduce the three-dimensionality and heterogeneity of the tumor microenvironment. Here we present a novel mechanism to address space and time constrains with 3D bioprinted organoid tumors (BOT) that mimic core needle biopsy tissue to reduce both cost and time to market for novel therapeutics making effective cancer therapy more accessible and equitable. The aim of this study is to produce and use BOT core biopsy tissue in ex vivo precision and personalized medicine applications. Methods: Bioinks prepared with MDA-MB-231 cells, fibrinogen, and thrombin will be deposited layer-by-layer on microporous substrate, in various geometrical configurations, and cured in stages to allow cells and matrix to self-assemble with limited degrees of freedom. Bioprinted organoid tissue will be fully cured to mimic patient biopsy cores, which will then be loaded in ex vivo bioreactors to evaluate sensitivity and resistance of small molecule and biologics. Results: Tissue 3D microarchitecture was validated using high-content fluorescence imaging and custom image processing applications. Diffusion of mock agents, small molecule, and nucleic acid stains was measured 200 mm deep in tissue. Differential activity in spatially distinct regions of intact BOT cores was quantified using advanced image processing modules. Conclusions: Patient derived BOT cores could be used both as a predictive model to screen drugs on an individualized basis and to uncover new therapeutic targets to improve efficacy and reduce toxicity. Due to their ability to replicate the physical and biochemical characteristics of a tumor and its microenvironment, BOT based precision and personalized medicine models can provide more accurate data on drug efficacy and toxicology when compared to in vitro cancer models.
A phase II feasibility study of electronic patient reported outcomes (ePROs) for oral cancer directed therapies (OCDT).
Authors: Doolin Jim W , Haakenstad Ellana , Neville Bridget A. , Lipsitz Stuart R. , Zhang Sunyi , Cleveland Jessica , Hiruy Semegne , Hassett Michael J. , Revette Anna C. , Schrag Deborah , Basch Ethan , McCleary Nadine Jackson 
Published: June 2022

e13509 Background: Patients receiving oral cancer directed therapy (OCDT) may be at greater risk of toxicity and non-adherence than those on intravenous treatments. Electronic patient reported outcomes (ePROs) have the potential to mitigate those risks by alerting clinicians to patient status between visits, prompting earlier intervention. Best practices for ePROs implementation are not yet defined. We sought to demonstrate the feasibility of ePROs between visits for patients receiving OCDT both without and with asynchronous nursing triage calls for severe symptoms. Methods: In this Phase II feasibility study, patients were prospectively enrolled into two arms. In the first arm, “passive management” (Arm 1) patients were sent weekly ePROs with 15 symptoms, graded 0 (none) to 3 (severe), through the electronic patient portal (ePP). Responses were available for review by clinicians via the electronic medical record (EMR). In the second arm, “active management” (Arm 2) patients received the same weekly ePROs. If a patient responded with a severe symptom, a nurse would call within one business day to triage the concern. The primary outcome was 30-day feasibility, defined as a patient responding to 50% or more of ePROs sent during this period. Secondary outcomes included feasibility at 60- and 90-days, unplanned healthcare utilization (urgent care, ED visit or hospitalization), and nursing calls. At the time the Arm 2 was enrolling, a language-concordant interface for the EMR and ePP became available. The study was amended to include primarily Spanish speaking patients with a language concordant ePROs survey. Results: 100 patients were enrolled, 50 per arm. 10 patients who primarily spoke Spanish were included in Arm 2; the remaining 90 patients were fluent in English. 96 patients were eligible for evaluation of 30-day feasibility, 92 for 60-day, and 86 for 90-day. The 30-day feasibility by arm was 57% in Arm 1 and 45% in Arm 2 (p = 0.26). The 30-day feasibility in the Spanish language subgroup of the Arm 2 was 56%. Nursing calls in the first 30-days were 101 in Arm 1 and 109 in Arm 2. Multivariable regression for predictors of responding to 50% or more of ePROs in days 0-30 did not identify statistically significant correlates of feasibility. Conclusions: ePROs administered via an ePP were feasible the first 30 days on oral cancer directed treatment. Adding nurse triage calls between visits and a language concordant process for primarily Spanish speaking patients were feasible. Larger studies are needed to determine which factors truly impact use of the program and, most importantly, adherence and quality of life.[Table: see text]