bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes to first-line pembrolizumab in patients with PD-L1-high (≥50%) non-small-cell lung cancer and a poor performance status.
Authors: Alessi Joao Victor Machado , Ricciuti Biagio , Jimenez Aguilar Elizabeth , Hong Fangxin , Wei Zihan , Nishino Mizuki , Plodkowski Andrew J. , Sawan Peter , Luo Jia , Rizvi Hira , Carter Brett W. , Heymach John , Altan Mehmet , Hellmann Matthew David , Awad Mark M. 
Published: May 2020

9568 Background: Patients with non-small cell lung cancer (NSCLC) and a poor Eastern Cooperative Oncology Group performance status (ECOG PS) have been excluded from immunotherapy clinical trials. We sought to evaluate clinical outcomes to first-line pembrolizumab in patients with advanced NSCLC, a PD-L1 tumor proportion score (TPS) of ≥50%, and an ECOG PS of 2. Methods: We performed a multicenter retrospective analysis of patients with metastatic NSCLC and a PD-L1 tumor proportion score (TPS) of ≥50% (negative for genomic alterations in EGFR and ALK) who received treatment with first-line commercial pembrolizumab. Clinical outcomes were compared in patients based on ECOG PS. Results: Among 234 patients, 83.3% (N = 195) had an ECOG PS of 0 or 1, and 16.7% (N = 39) had an ECOG PS of 2. The baseline clinicopathological characteristics were balanced between the ECOG PS 0-1 vs 2 groups in terms of age, sex, tobacco use, histology, KRAS mutation status, presence of other potentially targetable driver mutations ( BRAF, MET, HER2, RET), history of central nervous system (CNS) disease, and PD-L1 TPS distribution. Compared to patients with an ECOG PS of 0-1, patients with an ECOG PS of 2 had a significantly lower objective response rate (ORR 43.1% vs 25.6%; P = 0.04), a numerically shorter median progression free survival (mPFS 6.6 months vs 4.0 months; P = 0.09), and a significantly shorter median overall survival (mOS 20.3 months vs 7.4 months; P < 0.001). Upon disease progression, patients with an ECOG PS of 2 were significantly less likely to receive second-line systemic therapy compared to patients with an ECOG PS of 0-1 (55.5% vs 14.3%, P < 0.001). Conclusions: Although a subset of patients with an ECOG PS of 2 can respond first-line pembrolizumab, clinical outcomes in this population are poor, and use of second-line systemic therapy is infrequent.
Efficacy and safety of alflutinib (AST2818) in patients with T790M mutation-positive NSCLC: A phase IIb multicenter single-arm study.
Authors: Shi Yuankai , Hu Xingsheng , Zhang Shucai , Lv Dongqing , Zhang Yiping , Yu Qitao , Wu Lin , Liu Li , Wang Xiang , Ma Zhiyong , Cheng Ying , Niu Hongrui , Wang Dong , Feng Ji Feng , Huang Cheng , Liu Chunling , Zhao Hui , Li Jingzhang , Zhang Xiaodong , Jiang Yong 
Published: May 2020

9602 Background: Alflutinib (AST2818) is a third generation EGFR-TKI. This phase IIb, multicenter, single arm study (ALSC003, NCT03452592) aimed to assess the efficacyand safety of Alflutinib in patients with EGFR T790M mutated non-small cell lung cancer (NSCLC). Methods: Patients with locally advanced or metastatic EGFR T790M mutated NSCLC who progressed after first/second-generation EGFR-TKIs therapy or primary EGFR T790M mutation positive received 80 mg Alflutinib orally once daily. Tumor tissue samples underwent central laboratory testing for EGFR T790M mutation. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Efficacy was assessed by independent radiological review committee per RECIST 1.1. Safety was assessed by NCI CTCAE version 4.03. Results: From Jun 4, 2018 to Dec 8, 2018, 220 patients were enrolled with a median age of 61.0 (range 29 to 80) years. According to the AJCC version 8 staging system, 212 (96.4%) cases were in stage IV, and 8 (3.6%) cases in stage III. All patients had EGFR T790M mutation. By April 12, 2019, the ORR was 73.6% (95% CI 67.3–79.3). The DCR estimated at 6 and 12 weeks were 87.3% (95%CI 82.1-91.4) and 82.3% (95%CI 76.6-87.1), respectively. The median PFS was 7.6 months (95% CI 7.0–NA). Median OS and DoR have not been reached. 209 (95.0%) patients had at least one adverse events (AEs), which were mostly grade 1 or 2 and well tolerable. The most common AEs were increased aspartate aminotransferase (33 [15.0%]), upper respiratory tract infection (33 [15.0%]), and cough (33 [15.0%]). Grade 3 to 5 AEs occurred in 42 (19.1%) patients. The most common one was elevated γ-glutamyltransferase (n = 4). There were 3 deaths patients, 2 of which possibly not be related to the study drug, and 1 could not be determined. No interstitial pneumonia was reported. Conclusions: Alflutinib has promising efficacy and acceptable safety profile for the treatment of EGFR T790M mutated NSCLC patients. Clinical trial information: NCT 03452592 .
Effect of genomic and transcriptional alterations in first-line chemotherapy on subsequent immunotherapy in non-small cell lung cancer (NSCLC) patients.
Authors: He Yayi , Li Xiaobin , Dang Shiying , Liu Guifeng , Song Lele , Zhu Bo , Zhou Caicun 
Published: May 2020

9614 Background: Recent studies have demonstrated that first-line immunotherapy has better therapeutic response than second-line immunotherapy in NSCLC patients. However, the mechanism behind this observation has not been elucidated. The aim of this study is to investigate the mechanism of unfavorable influence that the first-line chemotherapy exerts on subsequent immunotherapy. Methods: 29 NSCLC patients without tyrosine kinase inhibitor (TKI)-related driver gene (EGFR, ALK, ROS1, RET, BRAF, C-MET) mutations were enrolled in this study. Paired cancer tissues before and after chemotherapy were collected, and NGS-based WES and mRNA sequencing were performed. Sequencing data were analyzed with R packages and statistics analysis was performed with SPSS 20 software. P ≤ 0.05 was regarded as statistically significant. Results: We found that the total number of SNV/INDEL mutations and the tumor mutational burden (TMB) decreased significantly following chemotherapy. The decrease of mutation burden correlated well with therapeutic response: patients with partial response (PR) exhibited significant decrease while patients with stable disease (SD) or progression of disease (PD) did not. Meanwhile, a sharp decrease in common mutations before and after chemotherapy was observed in PR and PD patients, but not SD patients, suggesting that mutational change reflected the therapeutic response. The change in copy number variations (CNVs) exhibited similar trends and correlation with therapeutic response. Subsequent analysis on mRNA levels revealed a sharp decrease in the expression levels of genes related to antigen processing and presentation as well as other factors relevant to immunotherapy response. Pathway enrichment analysis showed that the genes with decreased expression mainly represented immune-related signaling pathways or biological processes. Conclusions: Our study revealed a possible mechanism underlying unsatisfactory multiple-line immunotherapy following chemotherapy, and indicated that first-line chemotherapy may influence the tumor microenvironment to exert unfavorable influence on subsequent immunotherapy.
SWOG S1400F (NCT03373760): A phase II study of durvalumab plus tremelimumab for previously treated patients with acquired resistance to PD-1 checkpoint inhibitor therapy and stage IV squamous cell lung cancer (Lung-MAP Sub-study).
Authors: Leighl Natasha B. , Redman Mary Weber , Rizvi Naiyer A. , Hirsch Fred R. , Mack Philip C. , Schwartz Lawrence Howard , Wade James Lloyd , Irvin William Johnson , Reddy Sreekanth , Crawford Jeffrey , Bradley Jeffrey D. , Stinchcombe Tom , Ramalingam Suresh S. , Miao Jieling , Minichiello Katherine , Gandara David R. , Herbst Roy S. , Papadimitrakopoulou Vassiliki , Kelly Karen 
Published: May 2020

9623 Background: The Lung Cancer Master Protocol (Lung-MAP) is designed to evaluate novel targeted therapies in patients with advanced squamous lung carcinoma. In the S1400F sub-study (non-match), we tested whether combined CTLA-4 and PD-1 inhibition with durvalumab plus tremelimumab (D+T) could overcome primary or acquired resistance to anti-PD-(L)1 therapy. Response, progression-free (PFS) and overall survival, and safety in the acquired resistance cohort are reported herein. Methods: Patients with previously treated squamous lung carcinoma, performance status (PS) 0-1, and adequate organ function that developed disease progression after ≥24 weeks of anti-PD-(L)1 monotherapy were eligible. Prior severe immune-related toxicities, intervening systemic therapy and combination chemo-immunotherapy were not permitted. Patients received D1500 mg + T75 mg IV q28 days for 4 cycles then D maintenance until disease progression. The primary endpoint was best objective response (RECIST 1.1). Interim analysis for futility was planned after 20 patients evaluable for response were enrolled. If no responses were observed, the cohort would stop enrolment. Results: 30 eligible patients were accrued to the acquired resistance cohort. Median age was 68 years, 60% of patients were male, 33% PS 0 and had received a median of 2 prior lines of therapy (maximum 4). Best response to prior anti-PD-(L)1 therapy was CR/PR/SD in 3/7/20 patients, with a median duration of anti-PD-(L)1 therapy of 8.6 months (5.2-30.4). No objective responses were seen with D+T; 47% had SD as best response. Median PFS was 2.0 months (95% CI 1.6-2.9) and survival 7.5 months (95% CI 5.3-8.7). Among the 14 patients with SD as best response, the median PFS calculated from first disease assessment is 2.8 months (95% CI: 1.4-3.9). Grade≥3 adverse events at least possibly related to protocol therapy were seen in 10/30 patients. These include 1 treatment-related death due to pneumonitis and 1 death not otherwise specified. Other adverse events include grade 3 confusion (1), dehydration (2), diarrhea (3), encephalopathy (1), weakness (1), hyperglycemia (1), hypoxia (1), lymphopenia (1), nausea, (1), neutropenia (1), thrombocytopenia (1), rash (1), vomiting (1), grade 4 dyspnea (1), leucopenia (1) and lymphopenia (1). Conclusions: D+T did not demonstrate activity in patients with acquired resistance to PD-1 checkpoint inhibitors and pretreated advanced squamous lung carcinoma. Clinical trial information: NCT03373760 .
Efficacy and safety of pegfilgrastim in prophylaxis of chemotherapy-induced neutropenia in breast cancer patients.
Authors: Xia Wen , Xu Fei , Yuan Zhongyu , Xu Ruilian , Jiang Yi , Wu Zhiyong , Lu Qianyi , Zheng Qiufan , Hong Ruoxi , Jiang Kuikui , Huang Jiajia , An Xin , Bi XiWen , Hong Yun , Pang Danmei , Zhang Anqin , Wang Xianming , Zhang Qing , Zhang Haibo , Wang Shusen 
Published: May 2020

e12511 Background: The role of secondary prophylaxis with pegfilgrastim (brand name: Jinyouli) in Chinese breast cancer patients has not been fully evaluated. We assessed the efficacy and safety of pegfilgrastim in secondary prophylaxis of chemotherapy-induced neutropenia in breast cancer patients. Methods: In the open-label, single-arm, multicenter trail, 319 patients were enrolled. Breast cancer patients who developed grades 3/4 neutropenia in the previous chemotherapy cycle were given a fixed dose of subcutaneous pegfilgrastim, 24-48 hours after receiving the same chemotherapy regimen in the subsequent cycle. A dose of 6mg/cycle was given to patients weighed ≥45kg, and a dose of 3mg/cycle was given to patients weighed <45kg. The primary end point was the incidence of grade 3/4 neutropenia and secondary end point was the incidence of febrile neutropenia (FN). Results: In patients who received prophylactic pegfilgrastim, the incidence of grade 3/4 neutropenia was reduced to 12.53% (95% CI, 9.1 to 16.7) and the incidence of FN was reduced from 6.58% (95% CI, 4.1 to 9.9) in the screening cycle to 0.94% (95% CI, 0.2 to 2.7)(Table). Among the 40 patients who still developed grades 3/4 neutropenia after receiving pegfilgrastim, the absolute neutrophil count (ANC) was not significantly different between patients with (n=10) or without (n=30) additional filgrastim treatment. The most common adverse events (AEs) associated with pegfilgrastim were bone pain and myalgia, which were prevalent in 10% to 15% of the patients. However, both AEs were mild or moderate (grades 1/2). Conclusions: Prophylactic administration of pegfilgrastim is effective and safe in reducing the risk of grades 3/4 neutropenia and FN in breast cancer patients after receiving chemotherapy. [Table: see text]
Predictors of adjuvant radiation therapy in the treatment of male breast cancer and its impact on outcomes: A propensity matched analysis.
Authors: Bakalov Veli , Jayakrishnan Thejus Thayyil , Abel Stephen , Hilton Christie , Rusia Bindu , Wegner Rodney E. 
Published: May 2020

e12516 Background: Male breast cancer (MBC) accounts for 1% of all breast cancers and there is a paucity of data on factors impacting the treatment strategies and outcomes. We hypothesized that adjuvant radiation therapy (Adj-RT) may improve survival outcomes and sought to examine predictive factors for Adj-RT receipt. Methods: We queried the National Cancer Database (NCDB) for patients with stages I-III MBC treated with surgery (breast conservation surgery- BCS or mastectomy-MS) within 180 days of diagnosis (years 2004-2015). Multivariable logistic regression identified predictors of adjuvant radiation therapy receipt. Multivariable Cox regression evaluated predictors of survival. Propensity matching for adj-RT accounted for indication biases. Results: We identified 6,217 patients meeting the eligibility criteria (1457 BCS vs. 4760 MS). The majority of patients were white (85%) and within the age range of 50-80 years (74%). Although Adj-RT was omitted for 30% of BCS patients, the utilization was higher compared to MS (OR=26, p-value=0.001). The predictors of Adj-RT use were – African American race, higher stage, higher grade, presence of lymphovascular invasion and ER/Her-2 positivity for the entire cohort and higher age, urban location and higher income for BCS. Adj-RT was associated with lower mortality in the propensity matched model (overall HR for BCS=0.28, p-value<0.001; overall HR for MS=0.62,p-value=0.001) and is shown in the table. Conclusions: This study demonstrates there may be an association between decreased mortality and Adj-RT in MBC undergoing BCS. Although this implies that Adj-RT should be routinely delivered, it appears to be omitted frequently and its use requires further investigation. The study also suggests a benefit to Adj-Rt after MS for stage-III MBC. [Table: see text]
Factors associated with the use of adjuvant neratinib in stage I-III HER2-positive breast cancer.
Authors: Stoen Ericson , Kagihara Jodi , Kabos Peter , Fisher Christine M. , Diamond Jennifer Robinson 
Published: May 2020

e12517 Background: HER2-positive breast cancers have a higher risk of recurrence, though systemic chemotherapy in combination with HER2-targeted agents significantly reduces this risk. Neratinib (N) is a small molecule inhibitor of HER2 that was shown in the ExteNET trial to improve invasive disease-free survival in patients with stage II-III breast cancer. The purpose of this study was to investigate factors associated with the use of adjuvant N in patients with HER2-positive breast cancer treated in the University of Colorado Health system (UCH). Methods: We performed a retrospective chart review of women diagnosed with stage I-III breast cancer who received adjuvant trastuzumab (T) between July 2016 and April 2019 at UCH to coincide with the approval of N in July 2017. We collected patient demographics, baseline characteristics, and cancer treatments. Results: A total of 350 patients were identified who received adjuvant T for treatment of stage I-III HER2-positive breast cancer within the inclusion timeframe. 234 patients (74.1%) were either ≥ T2 and/or node-positive at diagnosis as in the inclusion criteria of ExteNET. Of these, only 31 (13.3%) were prescribed adjuvant N within 2 months of completing adjuvant T. 81 (34.6%) received adjuvant pertuzumab (P) in addition to T. Of those who received N, 78.8% were ≥ T2 and 78.8% were node-positive. The average age of those receiving N was 49.3 versus 54.9 years in those not receiving N. Hormone receptor (HR)-positive disease was noted in 72.7% of those receiving N and 68.6% in those who did not (P = 0.624). The vast majority (97.0%) of patients were prescribed diarrheal prophylaxis with N. Patients receiving adjuvant N were less likely to have had a pathologic complete response (pCR) following neoadjuvant chemotherapy than those who did not receive N (23.1% versus 51.0%, P = 0.008). Of those who received N, 18 (54.5%) were treated at an academic hospital, where 34.2% of the total studied patient population was treated. Conclusions: The use of adjuvant N in patients with ≥ T2 or node-positive HER2-positive breast cancer in our patient population was low. Patients who did receive adjuvant N were more likely to have residual disease following adjuvant chemotherapy and be treated at an academic hospital. Despite the greater benefit of adjuvant N in HR-positive HER2-positive breast cancer in ExteNET, HR status did not correlate with the use of adjuvant N in our study. Trials assessing the additional benefit of adjuvant N in patients receiving adjuvant P or trastuzumab emtansine will likely be required prior to widespread use of adjuvant N.
A novel approach for 21-genes testing associated with prognosis in Chinese patients with ER-positive/HER2-negative breast cancer: A real-world study.
Authors: Zeng Yinduo , Li Qian , Wu Jiannan , Deng Heran , Wang Ying , Wu Wenjing , Zhao Jianli , Dinglin Xiao-Xiao , Qin Tao , Liu Qiang , Su Fengxi , Jia Weijuan , Yao Herui 
Published: May 2020

e12528 Background: We previously reported a Chinese version of 21-genes Recurrence Score (RS) provides reduction chemotherapy prescription in patients with ER-Positive/HER2-Negative node negative breast cancer, while Oncotype Dx was hardly to be reached. However, the impact on clinical outcome was not mentioned. Herein, we explored whether this 21-genes recurrence score (RS) impacted on prognosis in patients with this molecular subtype of breast cancer. Methods: From Jan 2013 to Aug 2018, 378 patients with ER-Positive/HER2-Negative early stage breast cancer were enrolled. All patients received a Chinese version of 21-genes RS test, which is a new method using RNA extracted from formalin-fixed paraffin-embedded tissue performed by SurExam Campany, Guangzhou, China. . The RS score for each patient was calculated based on expression level of 21-genes used in a prosperctively defined algorithm and calculate a recurrence score range from 0 to 100 and divided three risk groups according to TAILORs study.Distant metastases-free survival (DMFS) were correlated with the 21-genes RS by Kaplan-Meier (log-rank method), and Cox regression. Multivariable logistic regression was performed to determine factors correlated with RS testing and receipt of a high-risk RS. Results: Median patient age was 46 years (18 to 77 years). The Chinese version of 21-gene RS was generated for 378 patients: 61 (16.1%) low risk ( < 11), 241 (63.8%) intermediate risk (11 to 25), and 76 (20.1%) high risk (≥ 26). At a median follow-up of 40 months, the 4-year-rate of estimated DMFS was 100%, 98.7% and 92.9% in low risk, intermediate risk and high risk groups. Meanwhile, there was no difference in RFS among three risk groups. For all patients, 21-gene RS was associated with DMFS ( P = .021). In multivariable Cox regression models, 21-gene RS was independently prognostic factor of DMFS (hazard ratio, 5.375; 95% CI, 1.00 to 28.84; P = .05). Tumor size (>2cm vs ≤2cm, OR = 2.31, P = .005), high grade ( OR = 2.15, P = .013), ki67 index ( > 14% vs ≤14%, OR = 4.24, P = .002), progesterone receptor expression ( < 20% vs ≥20%, OR = 5.07, P < .001) were predictor of high risk of RS. Conclusions: The Chinese version of 21-genes RS is independently prognostic factor for DMFS patients with ER–positive/HER2-negative node negative breast cancer. Future study was needed to explore the impact of 21 gene RS on long-term prognosis.
Usage and factors associated with adjuvant bisphosphonate therapy among postmenopausal women diagnosed with early-stage breast cancer.
Authors: Panuganty Veera Durga Sravanthi , Lakkunarajah Suganija , Shanmuganathan Sumugan , Black Morgan , Nasreen Sharifa , Karp Igor , Vandenberg Theodore A. , Raphael Jacques , Fernandes Ricardo , Blanchette Phillip S. 
Published: May 2020

e12532 Background: Early Breast Cancer Trialist Collaborative Group meta-analysis suggested significant reduction in bone metastasis and breast cancer mortality among post-menopausal women diagnosed with early breast cancer when treated with an adjuvant bisphosphonate. Cancer Care Ontario and American Society of Clinical Oncology clinical practice guideline published in 2017, recommends the use of an adjuvant bisphosphonate in postmenopausal women who are candidates for adjuvant systemic therapy. Our goal was to evaluate trends and factors associated with adjuvant bisphosphonate usage since the guideline’s publication. Methods: This study is a retrospective review of postmenopausal women treated for early breast at the London Regional Cancer Program from 2017-2018. Univariate and a multivariable logistic regression models were used to investigate factors potentially associated with adjuvant bisphosphonate use including age, stage, grade, estrogen receptor, progesterone receptor, HER2 receptor status and previous use of adjuvant chemotherapy. The percentage of patients offered, receiving and declining therapy was also recorded and the time interval from surgery to start of bisphosphonate therapy (< 6 months, 6-12 months or >12 months). Results: We identified 286 postmenopausal breast cancer patients, of whom 75 (28%) received adjuvant bisphosphonate therapy. In our multivariable model, cancer stage [odds ratio (OR) stage II vs. I=2.26, 95% confidence interval (CI) 1.08-4.74) and OR Stage III vs. I=4.94, 95% CI 1.84-13.17] and previous use of adjuvant chemotherapy (OR=2.76, 95%CI 1.37-5.55) were significantly associated with adjuvant bisphosphonate use. Among 133 patients who received adjuvant systemic chemotherapy, 51% were offered adjuvant bisphosphonate and of these 81% patients accepted therapy. Among a total of 75 patients receiving adjuvant bisphosphonate therapy 19% initiated therapy within 6 months of surgery, 48% within 6-12 months of surgery, and 33% after 12 months following surgery. Conclusions: Stage and previous use of chemotherapy were significantly associated with adjuvant bisphosphonate therapy. Our study observes the potential underutilization of adjuvant bisphosphonate therapy and possible need to start treatment earlier in some patients. Further education and awareness of the clinical practice guidelines regarding adjuvant bisphosphonate therapy may be warranted and additional population-based study investigating treatment patterns and real-world effectiveness.