bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three days of CIV rh-Endostatin in combination with PD-1 antibody plus chemotherapy as first-line regimen for EGFR/ALK-negative, advanced or metastatic, non-squamous non–small cell lung cancer (NSCLC): A open label, multicenter, phase II and cohort study (ENPOWER).
Authors: Wang Dong , Feng Yan , Bai Yuju , Ma Hu , Huang Li , Zhu Tienian , Qian Haihong , Li Yanping , Fang Xinjian , Ren Biyong 
Published: June 2022

9031 Background: rh-Endostatin, an antiangiogenic agent, in combination with chemotherapy is recommended by the CSCO guideline as the first-line treatment for EGFR/ALK-negative, advanced or metastatic, non-squamous non–small-cell lung cancer (NSCLC). However, evidence supporting the application of rh-Endostatin plus PD-1 antibody in clinical settings has been limited. The ENPOWER study is an open-label, multicenter, phase II and cohort study to evaluate the efficacy and safety of three days of continuous intravenous infusion (CIV) of rh-Endostatin in combination with PD-1 antibody plus chemotherapy as the first-line regimen for EGFR/ALK-negative, advanced or metastatic, non-squamous NSCLC. Methods: ENPOWER was an open label, multicenter, phase II and cohort study. Patients with EGFR/ALK-negative, advanced or metastatic, non-squamous NSCLC were enrolled and assigned into the following two cohorts. Patients in Cohort 1 (PD-1 combination) received rh-Endostatin plus PD-1 antibody plus standard chemotherapy (Carboplatin or Cisplatin plus Pemetrexed) during the induction period up to 4 - 6 cycles and rh-Endostatin plus PD-1 antibody during the maintenance period until disease progression or intolerable adverse events. Those in cohort 2 different from in cohort 1 was not subject to PD-1 antibody. Results: 43 subjects were evaluable for efficacy analysis, with 15 in Cohort 1 (PD-1 combination) and 28 in Cohort 2. ORR and DCR was 53% and 93% in Cohort 1 (CR, 0; PR, 8; SD, 6; PD,1) and 39% and 86% in Cohort 2 (CR 0; PR 11; SD, 13; PD, 4), respectively. 50 subjects were included in safety analysis. The overall incidence of AEs of any grade was 89%. 92% of the patients in the cohort 1 and 85% in the cohort 2. The majority of AEs was grade 1 or 2. Adverse events of any grade that occurred in at least 10% of patients were neutropenia（76%），nausea/vomiting (61%), AST/ALT abnormal (33%), palpitate (28%), anemia (22%) and skin hypersensitivity (11%) in the cohort 1 and neutropenia（68%），nausea/vomiting (59%), AST/ALT abnormal (21%), palpitate (16%), anemia (40%) in the cohort 2, respectively. Adverse events of grade 3 or higher found in the cohort 1 were neutropenia (23%) and those were neutropenia (19%), AST/ALT abnormal (3%) and anemia (3%) in the cohort 2. Seemingly, Adverse events that occurred more frequently in the cohort 1 than in the cohort 2 were AST/ALT abnormal, palpitate and skin hypersensitivity. Conclusions: Three days of CIV rh-Endostatin in combination with PD-1 antibody plus chemotherapy for the first line treatment of EGFR/ALK negative, advanced or metastatic, non-squamous NSCLC could obtain the better improvement in the efficacy and result in the higher frequent in some of AEs. Clinical trial information: NCT: 04063449.
Effect of performance status (ECOG PS) on treatment outcome with second-line (2L) nintedanib (NIN) + docetaxel (DOC) for patients (pts) with lung adenocarcinoma after first-line (1L) immune checkpoint inhibitor (ICI) combination therapy.
Authors: Grohé Christian , Wehler Thomas , Henschke Sven , Dittrich Ina , Hammerschmidt Stefan , Aulmann Christoph , Dechow Tobias , Schiefer Conrad , Zander Ingo , Schuette Wolfgang , Atz Judith , Kaiser Rolf 
Published: June 2022

9092 Background: ICIs with or without chemotherapy represent 1L standard of care for patients with advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. Given the paucity of prospective randomized trials assessing second-line treatment options post-immunochemotherapy, non-interventional data may help support clinical decision making. Patients with ECOG PS > 1 are generally underrepresented in clinical trials relative to routine clinical practice. We therefore examined treatment outcomes with 2L NIN + DOC after 1L ICI combination therapy with respect to ECOG PS at baseline. Methods: In this analysis of Cohort C of the ongoing, non-interventional VARGADO study (NCT02392455), eligible pts had locally advanced, metastatic or locally recurrent adenocarcinoma NSCLC and received 2L NIN+DOC in routine clinical practice after failure on 1L ICI in combination with chemotherapy. The primary endpoint is 1-year survival rate (not yet mature). Tumor response was according to investigator review. Results: In 164 pts enrolled in Cohort C, median age was 63 years (range: 37 – 84), 100 pts (61.0%) were men, and 123 pts (75.0%) were ECOG PS 0–1. 146 pts (89.0%) had received prior 1L pembrolizumab-based combination therapy. Objective response rate (ORR) with 2L NIN+DOC was 35.4% (40/113 pts) in the overall population and 41.2%, 30.8% and 28.6% for pts with ECOG PS 0, 1 and > 1, respectively. Disease control rate (DCR) was 67.3% (76/113 pts) in the overall population and 76.5%, 65.4% and 50.0% for pts with ECOG PS 0, 1 and > 1, respectively. Median PFS was 4.7 months (95% CI: 3.4 – 5.3) in the overall population and 5.1 months (95% CI: 2.8 – 8.3), 3.7 months (95% CI: 2.5 – 5.3) and 2.1 months (95% CI: 1.3 – 6.5) for pts with ECOG PS 0, 1 and > 1, respectively. The median OS was 8.1 months (95% CI: 6.3 – 11.2) in the overall population and 9.1 months (95% CI: 5.4 – 14.5), 10.5 months (95% CI: 6.3 – 14.9) and 4.0 months (95% CI: 2.5 – 6.3) for pts with ECOG PS 0, 1 and > 1, respectively. Conclusions: Our results support 2L NIN+DOC as an effective treatment option in pts with advanced adenocarcinoma NSCLC following 1L ICI in combination with chemotherapy. ECOG PS > 1 was associated with lower ORR, DCR and shorter PFS and OS. These findings warrant further evaluation of the effect of ECOG PS on 2L treatment outcomes in patients after 1L ICI combination therapy. Clinical trial information: NCT02392455.
Clinical response to tepotinib according to circulating tumor (ct) DNA biomarkers in patients with advanced NSCLC with high-level MET amplification (METamp) detected by liquid biopsy (LBx).
Authors: Le Xiuning , Paz-Ares Luis , Van Meerbeeck Jan , Viteri Ramirez Santiago , Cabrera Galvez Carlos , Vicente Baz David , Kim Young-Chul , Kang Jin-Hyoung , Stroh Christopher , Juraeva Dilafruz , Bruns Rolf , Otto Gordon , Johne Andreas , Paik Paul K. 
Published: June 2022

9121 Background: Tepotinib, a potent, highly selective, oral, MET inhibitor, showed meaningful activity in patients (pts) with NSCLC with high-level METamp by LBx in VISION. Exploratory biomarker analyses are presented herein. Methods: Pts had 0–2 prior therapy lines, high-level METamp by LBx (Guardant360; MET copy number ≥2.5), and no MET exon 14 skipping or EGFR/ ALK alterations. Pts received tepotinib 500 mg once daily (450 mg active moiety). Primary endpoint was objective response by independent review; data cut-off: Aug 20, 2021. Exploratory biomarker analysis included LBx at baseline (BL), on treatment, and end of treatment (EOT). Early molecular response (eMR) was defined as undetectable METamp 6–8 weeks on treatment. Results: 24 pts were enrolled (median age: 63.4 years [yrs]; smokers: 88%; ECOG PS 1: 88%; adenocarcinoma: 67%). Treatment duration was ≥1 yr in five pts and ≥2 yrs in two pts (both ongoing). Overall, objective response rate (ORR) was 41.7% (95% CI: 22.1, 63.4). Treatment-naïve pts (n=7) had an ORR of 71.4% (29.0, 96.3), median (m) DOR was 14.3 months (2.8, not estimable [ne]), and mPFS was 15.6 months (1.4, ne). BL biomarker analyses according to clinical benefit (CR/PR/SD [n=11] vs PD/NE [n=13]) showed association with better outcomes in pts with focal METamp, or without MYCamp or RB1 mutation (Table). MYCamp/ RB1 mutation was detected in 4/7 pts with neuroendocrine/not otherwise specified histology; MYCamp in 2/3 pts with neuroendocrine histology. Low BL ctDNA mutant allele frequency (MAF) was associated with better outcomes. 14 pts had eMRs (ORR 71.4%); persistent METamp (n=4) was associated with lack of clinical response. 2/9 pts with EOT biomarker profiles had emerging resistance mechanisms (MET kinase domain mutations Y1230 and D1228); both had METamp re-emergence. Treatment-related adverse events included edema (composite term; any grade: 46%; Grade 3: 13%) and constipation (any grade: 17%; Grade ≥3: 0%). Conclusions: Tepotinib showed meaningful activity, especially in first line, in the first trial of a MET inhibitor in EGFR WT NSCLC with high-level METamp to enroll based on a convenient LBx assay. BL biomarker analyses indicated focal METamp, MYC/RB1 WT, and low ctDNA MAF were associated with improved outcomes. Serial LBx could monitor molecular response and evaluate resistance. Clinical trial information: NCT02864992. [Table: see text]
Merkel polyoma virus specific T-cell receptor transgenic T-cell therapy in PD-1 inhibitor refractory Merkel cell carcinoma.
Authors: Veatch Joshua , Paulson Kelly , Asano Yuta , Martin Lauren , Lee Bo , Hall Evan Thomas , Bhatia Shailender , Nghiem Paul , Chapuis Aude 
Published: June 2022

9549 Background: Merkel cell carcinoma is an aggressive neuroendocrine tumor of skin origin with most cases caused by the Merkel polyoma virus (MCPyV). While many patients benefit from PD-1/PD-L1 axis blockade, most patients do not respond or develop resistance. We sought to ask whether adoptive transfer of autologous T cells transduced with MCPyV specific T cells could lead to clinical responses in PD-1 inhibitor refractory patients. Methods: Five MCPyV positive, HLA-A02 patients with PD-1 inhibitor refractory metastatic Merkel cell carcinoma were treated with adoptive transfer of CD62L+ CD8+ and CD4+ autologous T cells transduced with a T cell receptor (TCR) targeting an HLA-A0201 restricted MCPyV epitope. Two different strategies were used to facilitate T cell expansion: In 3 patients, single fraction radiation was administered to a subset of lesions prior to T cell transfer. In 2 patients, lymphodepleting chemotherapy with cyclophosphamide and fludarabine was administered prior to T cell transfer. Anti PD-1/PD-L1 therapy was given 14 days after T cell infusion. Transgenic T cells were visualized in tumor biopsies by multiplex immunohistochemistry. Results: 5 patients were treated, with 4 patients receiving 100 million tetramer positive CD8+ T cells and one patient receiving 500 million cells. 3 patients received second infusions with between 300 million and 900 million tetramer positive cells. No dose limiting toxicities or cytokine release syndrome were observed. T cell persistence was lower in the 2 patients treated with lymphodepleting chemotherapy relative to the 3 patients treated with single fraction radiation. Transgenic T cells persisted at tumor sites greater than 1 month following transfer. 4 patients experienced progressive disease, and a single patient had a mixed response and greater than 1 year disease free interval following local therapy of an isolated site of progression. The responding patient was the only patient with class I MHC staining on tumor cells prior to treatment, and the site of local progression in that patient showed the presence of TCR transgenic T cells but loss of class I MHC expression. Conclusions: MCPyV specific transgenic T cells are safe, traffic to tumor sites, and can result in a clinical response, but their clinical activity may be limited by down-regulation of class I MHC expression on tumors. A future trial will address strategies to increase class I MHC expression on Merkel tumors. Clinical trial information: NCT03747484.
Outcomes of neoadjuvant (NA) and adjuvant (A) chemotherapy in geriatric patients with stage I-III triple-negative breast cancer (TNBC): A single institution experience.
Authors: Sam Christine , Sehovic Marina , Extermann Martine 
Published: June 2022

e12522 Background: Older breast cancer patients have greater risk for toxicity with perioperative chemotherapy and poorer outcomes for stage I-III TNBC due to medical comorbidities and declining organ function. It is not clear whether use of anthracycline based chemotherapy regimens (ABC) delivers better outcomes than non-anthracycline taxane-based chemotherapy regimens (TBC) in this population. Methods: A single institution retrospective review of TNBC patients ≥65 treated with adjuvant and neoadjuvant chemotherapy at Moffitt Cancer Center from 2009 to December 2018 was conducted. Demographic, comorbidity, treatment, and toxicity variables were collected. Treatment toxicity was defined as dose reductions, dose delays, early discontinuations, unplanned hospitalizations, and grade 3-4 heme and non-heme toxicities. Eligible patients had stage I-IIII TNBC, were ≥65, and received NA or A chemotherapy at MCC. A validated frailty index (FI) was used to calculate comorbidity score. Kaplan Meier was used to estimate overall survival by regimen received, with log rank test to compare ABC and TBC groups. Results: A total of 79 patients met criteria for analysis, with mean age of patients receiving treatment was 71 (range 65-88). 41.8% of patients had stage I disease, 36.7% with stage II, and 21.5% with Stage III. 76% of patients with Stage III, 51.7% of Stage II, and 18% of stage I disease received ABC. There was a trend toward higher toxicity events in patients receiving ABC compared to TBC regimens, although not statistically significant (see Table). The mOS for patients receiving ABC was 43.5mo and 63.0 mo for patients receiving TBC, although not statistically significant (p=0.212). Conclusions: Geriatric patients with stage I-III TNBC were mostly able to successfully receive NA or A chemotherapy, although TBC may have better tolerability. Patients receiving TBC also had better survival, although not statistically significant and potentially confounded by patients with earlier stage or less aggressive tumors receiving TBC.[Table: see text]
A prospective real-world study to assess the effectiveness and safety of trastuzumab biosimilar in the adjuvant treatment of HER2-positive breast cancer: Preliminary safety results.
Authors: Cardoso Ana Carolina Ferreira , Gagliato Debora De Melo , Brito Natália Mesquita , Lapa Maura Gonzaga , Magaton Érida Aparecida Pinto , Santos Renata Virgínia Cavalcanti , Castilho Vivienne Carduz 
Published: June 2022

e12524 Background: The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) defines a biosimilar as a biological molecule product that is highly similar to and has no clinically meaningful differences from an existing approved reference product. The trastuzumab biosimilar was the first oncology biosimilar approved in Brazil for HER2-positive breast cancer (BC) and advanced gastric cancer treatment. This study aimed to assess the effectiveness and safety of trastuzumab biosimilar (named as Zedora in Brazil) in the adjuvant setting among HER2-positive BC patients treated in Brazil. Methods: This is a national, multicentric, observational, and prospective real-world study. Patients with early-stage HER2-positive BC who received at least one dose of trastuzumab biosimilar as adjuvant therapy were eligible. At the present date, 126 of 170 planned patients were recruited. Here, we present the preliminary safety data of the first 42 patients recruited in the study. The safety endpoint is the occurrence of adverse events (AEs), and the safety population included all patients who received at least one dose of trastuzumab biosimilar. We analyzed the AEs collected from the signature of the consent form until the end of adjuvant treatment. Results: Baseline patient characteristics among the 42 evaluated patients included a median age of 48.5 years, with 78.6% of them having a node-negative disease. Most patients had hormone-receptor-positive tumors (71.4% estrogen-receptor-positive and 57.1% progesterone-receptor-positive). The number of patients undergoing conservative surgery (59.5%) was higher than mastectomy (40.5%). The most frequent histological BC subtype was invasive ductal carcinoma (97.6%). Neoadjuvant therapy included the trastuzumab biosimilar administration (25%) and the dual anti-HER2 block (trastuzumab biosimilar + pertuzumab) (68.8%). Only 6.3% of patients received the reference trastuzumab in neoadjuvant therapy. In total, 25/42 (59,5%) patients had at least one AE, two of them were serious AEs (4.8%). The incidence of grade 3 or 4 AEs was 35.7%, and no death occurred. The table lists the most reported AEs according to SOC (System Organ Class). Conclusions: The nature and severity of AEs observed were consistent with the known safety profile of trastuzumab. Clinical trial information: NCT03892655. [Table: see text]
Genomic and immunological characterization between primary and recurrent breast cancer.
Authors: Liu Danni , Zhang Jing , Peisu Suo , Chen Shifu , Peng Xiufan 
Published: June 2022

e12553 Background: A large number of breast cancer patients suffered cancer recurrence. Survival was seriously worse in recurred tumor. Immune microenvironment and pathways inducing drug resistance were closely related to tumor recurrence. It is necessary to clarify the recurrence mechanisms and improve recurrence detection. Methods: Somatic mutation, expression matrix and clinical information of primary (n = 1177) and recurred (n = 803) breast tumors in METABRIC were downloaded from cBioPortal. The Kaplan-Meier method of survival analysis was used to display overall survival. Significantly mutated genes (SMG) identified by MutSig2CV (v3.11) with Qvalue < 0.05. R packages CIBERSORT was applied to calculate the proportion of tumor-infiltrating immune cell using mRNA expression microarray data. Student's t-test was used to compare the SMGs expression log intensity levels of two groups. Results: Overall survival were significantly difference between the primary and recurred patients (log-rank test, P value < 0.0001). The immune cell components of primary and recurred breast tumors presented different patterns. Macrophages were significantly enriched in primary patients (Kruskal-Wallis test, P value < 0.05). PIK3R1, SMAD4, ATR and FLT3 were uniquely significantly mutated and expressed at lower levels in recurred group. These SMGs were identified as being associated with recurrence in other cancer studies. For example, PIK3R1 regulates the transduction of PI3K/Akt pathway, which disrupting the balance between induction and prevention of apoptosis, causing drug resistance. In the other, SMAD4 acts as a central mediator of TGF-β/SMAD4 signaling pathway that usually impedes immune cell activation. Conclusions: Recurred breast tumors presented different genetic mutation frequency and microenvironment. Tumor immune factors are associated with recurrence. Detecting uniquely SMGs of recurred breast tumors may be a feasibility way to monitor disease recurrence.
Quality initiative (QI) to improve molecular testing in newly diagnosed (ND) stage 4 non-small cell lung cancer (NSCLC-4): An Integra Connect (IC) database study.
Authors: Gart Mike , Choksi Rushir J. , Petro Daniel P. , Scott Jeffrey A. , Varughese Prateesh , Stockton Matt , Smith Robert E. 
Published: June 2022

e13507 Background: In August 2019 IC partnered with University of Pittsburg Medical Center (UPMC) on a QI aimed at improving outcomes in stages 3 and 4 NSCLC. This report details the findings, interventions, and results in the stage 4 cohort to date. Guidelines advocate broad molecular profiling and completion of biomarker testing prior to initiation of initial therapy (KF Mileham,2022). However, real world data has shown a high rate of treatment initiation without biomarker testing due to low rate of testing and, if tested, treatment prior to results reporting (H West,2021; J Nicholas, 2021) in this disease state having a 5-year survival of only 7% (N Howlander). Based on analysis of the US Oncology Network it was found that only 46% of patients (pts) with metastatic NSCLC received testing for PD-L1, EGFR, ALK, ROS1, and BRAF-V600E (J Nicholas, 2021). Methods: By querying the UPMC and IC databases, 847 patients (pts) with ND NSCLC-4 were identified who received an initial line of therapy, excluding squamous carcinoma pts unless documented never-smokers, during 1/1/2017- 12/31/2021. Date of EGFR test ordered, date of test result report to electronic health record, and date of treatment initiation were captured. Also included were test orders for the NCCN recommended biomarker panel of PD-L1, ALK, ROS1, BRAF, RET, MET, and NTRK. The data were evaluated in three time periods for the QI: Phase 1 of 1339 days (1/1/2017-8/31/2020) for baseline, Phase 2 of 122 days (9/1/2020-12/31/20) post physician leadership intervention, and Phase 3 of 272 days (1/1/2021-9/30/2021) performance measurement period. Baseline and on-going measurement of testing metrics was performed with physician leadership intervention for identified gaps in care. Additionally, surveys were implemented to assess caregiver perceptions. The use of chart curation and software-based monitoring tools powered by IC enabled providers to understand current levels of testing and track performance over time. Results: Median age was 68 (range 36 - 89) and 49% male. As shown in Data Table, EGFR testing at baseline was 94% and increased to 96%. Testing of the entire biomarker panel noted above increased from 52% baseline to 76% at this point in Phase 3. While only 72% had treatment initiated after EGFR result at baseline, this improved to 88% during Phase 3. Conclusions: This QI led to improvement in rates of broad biomarker testing and initiation of treatment only after results were made available in this NSCLC-4 population. While this initiative was not designed to evaluate outcomes, one would expect outcome improvement over baseline with higher guideline adherence.[Table: see text]
Enhancing accrual to clinical trials of minority patients with gynecologic malignancy.
Authors: Lara Olivia , Pothuri Bhavana 
Published: June 2022

e13535 Background: Central to improving survival of patients with gynecologic malignancy is participation in therapeutic, surgical and preventative clinical trials. Minority population accrual is particularly poor representing a disparity in cancer care. We sought to evaluate enrollment of minority populations at an urban NCI-designated Comprehensive Cancer Center before and after the NCI call to action June 2020. Methods: Data on patient enrollment in gynecologic oncology clinical trials (14 therapeutic and 4 non-therapeutic) was obtained from Perlmutter NCI-designated Comprehensive Cancer Center. Primary outcomes were the proportion of newly accrued patients by race participating in trials between January 2019 to September 2021. Results: Over the entire study period 154 total patients were enrolled in therapeutic and non-therapeutic clinical trials. Enrollment by cancer type included 100 (71.4%) ovarian, 16 (7.1%) uterine, 12 (7.9%) cervical and 26 (13.5%) solid tumor trials. White patients comprised 69% (69 of 100) of patients on ovarian cancer trials. Uterine cancer trials by race consisted of 50 % White, 37.5% Black, 6.2% Asian and 6.2% Other race patients. Eighty-eight patients were enrolled into clinical trial prior to the NCI alert. By race these patients were: White, 65.9% (58 of 88); Black, 3.4% (3 of 88); Asian, 11.4% (10 of 88) and Other race, 19.3% (17 of 88). Hispanic patients comprised 13.6% (12 of 88) of the population. Following the call to action an additional 66 patients were enrolled in clinical trial. This included 42 (63.6%) White, 14 (21.2%) Black, 5 (7.57%) Asian, 5 (7.6%) Other race and 8 (12.12%) Hispanic patients. The percentage of Black patients enrolled in clinical trial increased four -fold over the time period (3.4% vs 21.2%, p < 0.05). Conclusions: Overall during this time period we found an increase in number of Black patients accrued to clinical trial. This indicates disparities in clinical trial enrollment can be modified by institutional awareness. The role of patient education, financial and logistical barriers and language discordance to minority participation in clinical trials should be studied further.