bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes in patients with advanced non-small cell lung cancer (aNSCLC) and high PD-L1 expression treated with immune checkpoint inhibitor monotherapy: An FDA-pooled analysis.
Authors: Shah Sujay Yogesh , Vallejo Jonathon Joseph , Gong Yutao , Brown Thomas D. , Zhang Chenan , Hirsch Jonathan , Tang Shenghui , Blumenthal Gideon Michael , Singh Harpreet , Kluetz Paul Gustav , Theoret Marc Robert , Beaver Julia A. , Pazdur Richard 
Published: May 2020

9606 Background: Higher PD-L1 score ≥ 50% predicts for greater benefit to immune checkpoint inhibitor (ICI) therapy in first line (1L) treatment of aNSCLC. It has recently been reported that PD-L1 score ≥ 90% predicts for even greater benefit to 1L ICI monotherapy (Aguilar et al., 2019). We examined pooled clinical trial databases to examine the relationship between high PD-L1 expression across multiple ICI monotherapies in 1L and second line (2L) treatment of aNSCLC. Methods: Data was pooled from trials (five 1L and five 2L) of ICI for the treatment of patients with aNSCLC. We defined PD-L1 score as the proportion of tumor cell stained by the assay (total of four assays identified) and included patients in the analysis with PD-L1 score ≥ 50%. Tumor-infiltrating immune cell staining was not considered. Progression-free survival (PFS) and overall survival (OS) by line of therapy for patients with PD-L1 score ≥ 90% and patients with PD-L1 score 50-89% was analyzed. Results: A total of 1320 patients treated with ICI monotherapy were identified, 873 in 1L and 447 in 2L. Median follow-up was 9.6 months in 2L patients and 13.3 months in 1L patients. Patients receiving 2L ICI therapy with PD-L1 score ≥ 90% (N = 208) had longer PFS and OS compared to patients with PD-L1 score 50-89% (N = 239), with mPFS 7.1 vs. 4.2 months (HR = 0.66 [95% CI: 0.52-0.83]) and mOS NR vs. 15.8 months (HR = 0.66 [95% CI: 0.49-0.89]). 1L ICI therapy analysis revealed similar trends, as patients with PD-L1 score ≥ 90% (N = 405) had longer PFS and OS compared to patients with a PD-L1 score 50-89% (N = 468), with mPFS 8.3 vs. 5.4 months (HR = 0.78 [95% CI: 0.66-0.92]) and mOS 22.9 vs. 16.4 months (HR = 0.74 [95% CI: 0.61-0.90]). Conclusions: This analysis showed the potential of an enhanced clinical benefit in patients with aNSCLC and PD-L1 score ≥90% across ICI monotherapies in both the 1L and 2L treatment setting. These data will be further analyzed in real world populations.
Cabozantinib in combination with atezolizumab in non-small cell lung cancer (NSCLC) patients previously treated with an immune checkpoint inhibitor: Results from cohort 7 of the COSMIC-021 study.
Authors: Neal Joel W. , Lim Farah Louise , Felip Enriqueta , Gentzler Ryan D. , Patel Shiven B. , Baranda Joaquina , Fang Bruno , Squillante Christian Michael , Simonelli Matteo , Werneke Scott , Curran Dominic , Ponce Aix Santiago 
Published: May 2020

9610 Background: First-line immunotherapy with/without chemotherapy is standard of care for patients (pts) with advanced NSCLC; however, there is a need for effective treatment options after progression on a prior immune checkpoint inhibitor (ICI). Cabozantinib (C) may augment response to ICI by inhibiting kinases implicated in suppressing immune cell responses and has shown encouraging clinical activity in combination with ICI in other tumor types including RCC and HCC. COSMIC-021, a multicenter phase 1b study, is evaluating the combination of C with atezolizumab (A) in various solid tumors (NCT03170960). We report results from cohort 7 in NSCLC pts after prior ICI therapy. Methods: Eligible pts had ECOG performance status (PS) 0-1 and radiographic progression after one prior anti-PD-1/PD-L1 ICI given alone or in combination with chemotherapy for metastatic non-squamous NSCLC. Up to 2 lines of prior systemic anticancer therapies were permitted. Pts received C 40 mg PO QD and A 1200 mg IV Q3W. CT/MRI scans were performed Q6W for the first year and Q12W thereafter. Primary endpoint is ORR per RECIST 1.1 by investigator. Other endpoints include safety, duration of response (DOR), progression-free survival, and overall survival. Results: Thirty pts with advanced NSCLC were enrolled. Median age was 67 yrs (range 41, 81), 43% were male, 57% had ECOG PS 1, and 23% had liver metastases. Median duration of prior ICI therapy was 4.8 months (mo; range 0.8, 29), and 15 (50%) pts were refractory to prior ICI (progressive disease as best response). As of December 20, 2019, the median follow-up was 8.9 mo (range 5, 20) with 9 (30%) pts continuing study treatment. The most common treatment related adverse events (TRAEs) of any grade were diarrhea (53%), fatigue (37%), nausea (23%), decreased appetite (20%), palmar-plantar erythrodysesthesia (20%) and vomiting (20%). Grade 3/4 TRAEs occurred in 14 (47%) pts, and 1 (3.3%) had grade 5 TRAEs of myocarditis and pneumonitis. Confirmed ORR per RECIST 1.1 was 23% (7 of 30 pts; all partial responses including 3 pts refractory to prior ICI). Time to response was 1.4 mo (range 1, 3), and median DOR was 5.6 mo (range 2.6, 6.9). DCR (CR+PR+SD) was 83%. Conclusions: The combination of C and A had an acceptable safety profile and showed encouraging clinical activity in pts with advanced NSCLC who had progressed after prior ICI therapy. The response rate was greater than previously observed with C monotherapy. Due to the promising data, enrollment in this cohort has been expanded and is ongoing. Clinical trial information: NCT03170960 .
Adjuvant chemotherapy with or without an anthracycline in older adults with node-negative triple-negative breast cancer (TNBC): A SEER Medicare study.
Authors: Schreiber Anna R , Kagihara Jodi , Eguchi Megan , Kabos Peter , Meyer Elisabeth , Kondapalli Lavanya , Fisher Christine M. , Bradley Cathy J , Diamond Jennifer Robinson 
Published: May 2020

e12505 Background: TNBC is an aggressive breast cancer subtype comprising approximately 15% of breast cancers. Adjuvant chemotherapy reduces the risk of recurrence, particularly in patients with tumors > 1 cm or node positive disease. Anthracycline (A) + taxane (T)-containing regimens are more efficacious than T-based regimens, however, the risk of cardiac toxicity is greater in older patients. We investigated the use of AT and T-containing regimens in patients ≥ 66 years old with node negative TNBC and evaluated clinical outcomes and cardiac risk factors. Methods: We identified female patients ≥ 66 diagnosed between 2010-2015 with TNBC node negative disease in the Surveillance, Epidemiology, and End Results (SEER) Medicare database. Baseline characteristics, including age, tumor size, cardiac history, and adjuvant chemotherapy administration (AT vs. T) were collected. A logistic regression analysis was performed to estimate independent predictors of AT vs. T chemotherapy. Overall survival (OS) was estimated at 3 years. Results: We identified 3348 patients, including 1679 (50.2%) who received chemotherapy for T1a/bN0 (32.5%), T1cN0 (55.5%), T2N0 (57.0%) and T3/T4N0 (49.6%) disease. Of those, 984 (58.6%) received T, 420 (25.0%) received AT and 275 (16.4%) received other chemotherapy. AT use was associated with larger tumor size; T1a/bN0 (13.6%), T1cN0 (21.3%), T2N0 (31.6%) and T3/T4N0 (34.9%). In a multivariate analysis, independent predictors of AT vs. T were age, region treated in the USA, tumor size and presence of prior cardiac risk factors or pre-existing cardiac disease. OS at 3 years was 91% for T and 86% for AT (p 0.03). Conclusions: Approximately half of older patients diagnosed with node negative TNBC received adjuvant chemotherapy. T-based regimens were more commonly used than AT regimens. Younger age, higher stage and lack of cardiac comorbidities correlated with use of AT compared to T. Continued investigation of the benefit of adjuvant chemotherapy in older patients may assist in clinical decision making.
Endocrine therapy adherence of premenopausal Mexican breast cancer patients.
Authors: Villarreal-Garza Cynthia , Mesa-Chavez Fernanda , Ferrigno Ana Sofia , De la Garza-Ramos Cynthia , Villanueva-Tamez Karen , Fonseca Alan , Campos-Salgado Jose Yair , Pineda Claudia , García-García Marisol , Rodriguez David Omar , Cruz-Ramos Marlid , Cabrera-Galeana Paula 
Published: May 2020

e12510 Background: Among premenopausal women with breast cancer (BC), adherence to endocrine therapy (ET) has often been reported suboptimal due to age-related adverse effects, lack of understandable information and inadequate social support. The current increased use of ovarian function suppression (OFS) may lead to even lower adherence rates in this group due to its high adverse effects profile. This study aims to assess the extent to which premenopausal patients comply with ET and to identify factors that hinder optimal adherence in Mexico. Methods: Women aged ≤50 years with primary stage I-III hormone receptor-positive BC receiving adjuvant ET for ≥1year were invited to fill a survey regarding their attitude towards ET and self-reported adherence. Fisher’s exact test was used to explore associations between categorical variables. This study was funded by AstraZeneca Mexico. Results: From Sep 2019 to Jan 2020, 127 patients with a median age of 45 years (range: 25-50) were included. Most had at least high school education (64%) and were unemployed (61%). ET distribution was: 69% tamoxifen (TMX) alone; 2% TMX switch to aromatase inhibitor (AI); 29% OFS plus TMX/AI. All patients recognized ET as a necessary part of their treatment and 97% believed it reduced their recurrence risk, yet 14% considered they had not received enough information about ET. Adverse effects were reported by 98%, predominantly hot flashes (82%), arthralgias (59%) and fatigue (58%). A statistically significant higher proportion of patients treated with a switch strategy or OFS experienced hot flashes, headache, insomnia, decreased libido and dyspareunia than those with TMX alone. Only 59% claimed their physician had taken measures to reduce these symptoms. Overall, 93% reported complete ET adherence. Nonetheless, 22% of them subsequently acknowledged missing 1-6 doses in the last month, the most common reasons being forgetfulness (78%), adverse effects (27%) and unwillingness to take the medication (11%). Unemployed patients were more likely to report daily compliance than students/employees (79% vs 60%; p = 0.02). No significant differences in adherence were found according to other factors, including type of ET. Conclusions: Premenopausal Mexican women self-report remarkably high rates of ET adherence. However, a considerable proportion misses ≥1 doses/month, with forgetfulness as the most common cause particularly in students/employees. Interventions aimed at reminding this group to take their ET and managing adverse effects could be crucial to improve adherence and, consequently, disease outcomes.
SEER-Medicare study of early-stage triple-negative breast cancer: Real-world treatment patterns, survival, and expenditures 2010 to 2016.
Authors: Sieluk Jan , Haiderali Amin , Huang Min , Yang Lingfeng , Tryfonidis Konstantinos , Hirshfield Kim M. 
Published: May 2020

e12512 Background: In the US, triple-negative breast cancer (TNBC) represents about 10–20% of breast cancers. Current information about the clinical and economic burden of early-stage TNBC in elderly patients is lacking. Methods: We used the SEER-Medicare database to identify patients with continuous Medicare Parts A/B enrollment, ≥66 years old, newly diagnosed between 2010 - 2015 (followed until 2016) with stage II-III TNBC, who initiated systemic neoadjuvant and/or adjuvant (including chemotherapy and radiation) therapy. Overall survival (OS) and event-free survival (EFS) from diagnosis were estimated using Kaplan-Meier (KM). Healthcare costs were determined during neoadjuvant and adjuvant periods. Results: Of 1569 patients ( > 99% women), 94 (6%) received neoadjuvant therapy, 1162 (74%) received adjuvant therapy, and 313 (20%) received both (neo/adj; Table). Age and race/ethnicity distributions were comparable in the three cohorts. Primary tumor T stage was T1c/T2 for 43%, 83%, and 58% in neoadjuvant, adjuvant, and neo/adj, respectively, and T3 for 14%, 10%, and 15%, respectively. The most common systemic regimens in both neoadjuvant and adjuvant periods were a taxane +/- anthracycline; 21% and 67% of patients in adjuvant and neo/adj cohorts received radiation therapy after surgery. Most claims were for outpatient treatment; hospitalizations were uncommon. The total mean expenditures per patient per month were US$10,620 and $24,408 during neoadjuvant and adjuvant periods, respectively. Conclusions: This study provides insights into patient characteristics, as well as clinical and economic outcomes for elderly patients with early-stage TNBC, treated from 2010-2016 in the US, highlighting the high monetary burden of TNBC and poor outcomes associated with stage III patients. [Table: see text]
RelB silencing to reverse tamoxifen resistance by regulating GPx4 and ferroptosis in breast cancer.
Authors: Xu Zhi , Tang Jinhai 
Published: May 2020

e12513 Background: Tamoxifen(Tam), as an essential therapeutic treatment of estrogen receptor(ER)-positive breast cancer(BCa), has been available for the past three decades. However, the induction of Tam resistance during therapy has indicated a significant challenge with regards to this agent. Tam could increase oxidative stress and induce cell death by regulating reactive oxygen species(ROS). Ferroptosis, a cell death process driven by the accumulation of iron-dependent lipid peroxides, has been induced by inactivation/depletion of glutathione peroxidases(GPxs). Our previous studies found that the expression level of RelB gene, a member of NF-κB family, is negatively correlated with ER targeted by Tam in BCa. Methods: The RelB level of BCa tumor tissues and the corresponding cell lines were examined by immunoblotting and western blot. The effects of Tam on cell viability were determined using colony survival and MTT assay. The ROS and oxygen consumption rates(OCR) were measured using specific ROS detection probes and a Seahorse XF96 Analyzer, respectively. The lipid peroxidation level of cells was analyzed by immunofluorescence assay. The morphological changes of mitochondria were observed by transmission electron microscope. RelB binding to the NF-κB intronic enhancer region of the human GPx4 gene was determined using a ChIP assay. Accordingly, the effect of RelB on BCa Tam resistance was further validated using BCa mice xenograft models. Results: RelB was uniquely expressed at the high level in Tam resistance BCa tissues and cell lines. Down-regulation of RelB based on a CRISPR/Cas9 system remarkably sensitized resistance BCa cells to Tam. Treatment with SN52, a RelB inhibitor, illuminated the role of RelB in Tam-treated BCa cells. The high level of ROS and declination of mitochondrial respiration which induced by Tam were inhibited in resistance cells. Tam enhanced lipid peroxidation with concomitant non-apoptotic cell death, which are negatively regulated by GPx4 activity. In addition to GPx4 knockdown, deferoxamine was able to rescue Tam-induced cell death in BCa cells, verifying that Tam induces cell death partially through ferroptosis. Importantly, RelB upregulates GPx4 expression through binding to an NF-κB enhancer element located at the 5’-flanking region. Consistently, in vivo functional validation confirmed that RelB inhibition not only impairs tumor growth, but also inhibits Tam resistance in nude mice. Conclusions: RelB could inhibit ferroptosis which induced by hydroxyl radicals accumulation through upregulating GPx4 in BCa.
Practice-changing use of 21-gene oncotype DX breast recurrence score assay in a public hospital in Brazil: Results of 155 cases.
Authors: Mattar Andre , Fonseca Guilherme Ribeiro , Romão Murilo Barato Agudo , Shida Jorge Yoshinori , Stiepcich Monica Maria Agata , Jakubowski Debbie M , Chao Calvin Y. , Oliveira Sergio C , Gebrim Luiz Henrique 
Published: May 2020

e12518 Background: The 21-gene assay estimates risk of recurrence expressed as a Recurrence Score result between 0 and 100. The assay is clinically validated to predict chemotherapy (CT) benefit in node-negative (N0) and node-positive (up to three axillary nodes, N1) hormone receptor-positive (HR+) early-stage breast cancer (ESBC). The TAILORx study, which randomized 6711 women with N0 ESBC and Recurrence Score result 11-25 to hormonal therapy (HT) ± CT, demonstrated that patients older than 50 years derived no benefit from CT+HT, although younger patients with Recurrence Score result 16-25 may derive some benefit. The 21-gene assay has been incorporated in practice guidelines worldwide, based on evidence of clinical utility in N0 and N1 ESBC. We evaluated the impact of the 21-gene test on treatment decisions for patients with N0 and N1 ESBC at Sistema Único de Saúde in Brazil. Methods: Eligible patients were post-surgery with T1/T2 tumors, had HR+, HER2−, N0 or N1 ESBC, and were candidates for adjuvant systemic therapy. Treatment recommendations, CT+HT or HT alone, were captured before and after 21-gene test results. All patients were seen at Pérola Byington Hospital, a public hospital in São Paulo, Brazil. TAILORx results were used to guide decisions for or against CT for each patient. Results: From 08/2018 to 04/2019, 155 women were enrolled. Patient mean age was 57.6 years (29-78), 116 (75%) were postmenopausal, and 53 (34%) had N1 breast cancer. Based on clinical data alone, 151 patients had pre-assay recommendations of CT. Post-assay, 106 of 151 patients (70%) had changes in CT recommendation: 104 (69%) initially recommended CT received HT alone, and 2 (1%) initially recommended HT alone received CT+HT (Table). Using the modified Adjuvant!Online criteria for clinical risk classification, 109 of 155 patients (70%) had high risk, 48 (44%) of whom received CT. Of 46 patients with low clinical risk, 10 (22%) received CT. CT use trended with histologic grade: 11% with grade 1, 69% with grade 2, and 61% with grade 3. Most of our patients had tumor bigger than 2 cm (61%) with 8% bigger than 4 cm. Conclusions: The change in clinical practice at this public hospital was greater than expected: 69% of initial treatment recommendations were changed with the Recurrence Score result to omit CT. Clinicopathologic criteria did not correlate well with Recurrence Score results and did not identify those most likely to benefit from CT. A cost-effectiveness study is underway at our institution. [Table: see text]
Nine weeks versus six months of adjuvant trastuzumab in HER2-positive breast cancer: 3-year disease-free survival results.
Authors: Saifo Maher 
Published: May 2020

e12530 Background: A total of 12 months adjuvant trastuzumab is still the optimal choice for patients with HER2-positive early breast cancer. However, the shorter course of 9 weeks may be considered as a cost-effective and safe option in developing countries such as Syria. Purpose: We aimed at investigating whether short-course 9-week adjuvant Trastuzumab is non-inferior to 6-month treatment at Albairouni University Cancer Center. The primary endpoint was disease-free survival (DFS). The secondary objective was assessing toxicities, especially cardiotoxicity. Methods: Patients with HER2-positive stage I-IIIC breast cancer were assigned to receive either 9 weeks or 6 months of trastuzumab in combination with adjuvant chemotherapies (sequentially). The 9-week group; 90 patients received trastuzumab intravenously (loading dose 4 mg/kg; then 2mg/kg weekly), whereas in the 6-month group; 157 patients, trastuzumab was delivered every 3 weeks intravenously (loading dose 8 mg/kg then 6 mg/kg). The LVEF was measured pretreatment and every 3 months afterwards. Results: 3-year DFS was 71.87% in the 9-week group versus 76.43% in the 6-month group, (Non-significant). No obvious side effects have been noticed during the follow-up period in the 9-week group. Congestive heart failure was reported in 2.55% of patients in the 6-month group. Conclusions: Short-course 9-week adjuvant trastuzumab is less effective than 6 months of treatment, with less cardiotoxicity. The short course could be considered in patients with heart disease and low risk of recurrence.
Effect of farrerol on the proliferation of estrogen receptor-positive breast cancer by downregulating oncogenic genes with estrogen receptor response elements.
Authors: Lu Xiao-Qing , Yang Rui , Zhang Jia-Qian , Zhang Shengxiao , Zhang Huan-Hu 
Published: May 2020

e12541 Background: Breast cancer (BC) is the most common malignant tumor among women worldwide, the most common of which is estrogen receptor (ER) -positive BC. Farrerol, a noval estrogen-like chemicals, is closely associated with ER positive BC. In this study, we will explore the anticancer effect of farrerol on ER-positive BC and the detailed mechanism. Methods: Cloning formation assay and MTT assay were used to evaluate the effect of farrerol on proliferation ofcells. The affinity of farrerol, estrogen and tamoxifen with ER was tested by molecular docking technique. Point mutation was performed on the possible binding sites of ER according to the results of virtual docking, and Surface Plasmon Resonance (SPR). ER response elements in BC cells with farrerol were evaluated by qPCR. Results: With the increased farrerol concentration, the number of cell clones formed gradually decreased and the volume of clones became smaller in the ER positive McF-7 cell group, while a completely opposite clones was observed in non- ER positive MDA-MB-231 cells. The proliferation inhibition rate of McF-7 cells in the 160 mol/L and 320 mol/L groups was 45.86% and 65.3% respectively, significantly higher than that of MDA-MB-231 and normal mammary epithelial cells (P < 0.05). Both molecular docking technique and SPR experiment showed that farrerol could bind to ER at different sites than estrogen binding. Fiarrerol effectively down-regulated the transcription of the oncogenes MYC and TFF1, and suppressed ER-positive BC. Conclusions: Farrerol has the opposite effect with estrogen, which inhibited the proliferation of ER-positive BC cells, and downregulated the expression of oncogenic genes with ER response elements in BC cells. Therefore, farrerol, as a natural ingredient, could be further developed and applied with its obvious inhibitory effect on ER-positive BC in the future.