bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I/II study of SAR439859, an oral selective estrogen receptor degrader (SERD), in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC).
Authors: Campone Mario , Bardia Aditya , Ulaner Gary A. , Chandarlapaty Sarat , Gosselin Alice , Doroumian Séverine , Pelekanou Vasiliki , Celanovic Marina , Linden Hannah M. 
Published: May 2020

1070 Background: SERDs competitively antagonize and degrade the ER and can block signaling in ER-dependent tumors resistant to standard endocrine therapy (ET). This study (NCT03284957) investigates SAR439859, a potent oral SERD, in ER+/HER2- mBC. We present pooled dose escalation/expansion (Part A/B) data for SAR439859. Methods: Postmenopausal patients (pts) with ER+/HER2- mBC treated for ≥ 6 mos with prior ET received SAR439859 ≥ 150 mg QD (Part A) or 400 mg QD (Part B). Chemotherapy and targeted therapy in the advanced setting were allowed. Objective response rate (ORR; RECIST v1.1), clinical benefit rate (CBR; complete or partial response [PR] or stable disease [SD] ≥ 24 weeks), safety, and pharmacokinetics (PK) were assessed. Results: Pts (n = 62; Part A, 13; Part B, 49) had a median age of 63 yrs (range 37–88) and ECOG PS 0 (59.7%) or 1 (40.3%); 93.5% had visceral disease. All had prior ET, 74.2% had prior targeted therapy and 48.4% had ≥ 3 prior lines in the advanced setting. 61.3% of pts had treatment-related adverse events (TRAEs), all grade 1–2. Most frequent: hot flush (16.1%), constipation, arthralgia (both 9.7%), decreased appetite, vomiting, diarrhea, nausea (all 8.1%), fatigue (6.5%). No pts discontinued due to AEs. CBR was 35.6% overall, with antitumor activity irrespective of ESR1 mutation status (Table). In pts with no prior SERD, CDK4/6 or mTOR inhibitors (n = 14), ORR was 21.4% and CBR 64.3%. PK data for Part B and ESR1 mutation data will be provided. Conclusions: SAR439859 had a favorable safety profile with limited TRAEs. In these heavily pre-treated pts (prior targeted therapy in 74.2%), ORR and CBR were similar to historical fulvestrant performance in pts with no prior targeted therapy. Encouraging ORR and CBR in pts with no prior SERD, CDK4/6 or mTOR inhibitors (n = 14; ORR 21.4%; CBR 64.3%) supports SAR439859 development in earlier lines of therapy. Clinical trial information: NCT03284957 . [Table: see text]
Evaluation of DNA repair biology signatures to predict specific carboplatin (C) versus docetaxel (D) benefit in advanced triple-negative breast cancer (aTNBC).
Authors: Tovey Holly , Parker Joel S. , Hoadley Katherine A. , Kennedy Richard D. , Sipos Orsolya , Kilburn Lucy , Kernaghan Sarah , Gazinska Patrycja , Haider Syed , Pinder Sarah E , Bliss Judith , Perou Charles M. , Grigoriadis Anita , Tutt Andrew , Cheang Maggie Chon U ,   on behalf of the TNT trial management group
Published: May 2020

1074 Background: In the Triple Negative Trial we observed no improved response rate (RR) to C over D in aTNBC [Tutt et al, Nat Med 2018], but we did in BRCA1/2 mutated (mut) patients (pts). We hypothesise tumors with other aberrant DNA damage response (DDR) characteristics having higher RR to DNA damage inducing C than D. Methods: We tested the predictive value of DDR process related gene expression signatures (PARPi7, chromosomal instability CIN70, TP53 & DDR Deficiency (DDRD)) on 192 treatment naïve primary tumours (PT) by total RNA-sequencing. Odds ratio (OR) for RR are reported. Paired PT & recurrent (REC) signature scores were compared. Results: Unexpectedly, high DDRD and PARPi7 were associated with higher RR to D than C ( p =0.01 & 0.06). No effect was observed for CIN70 or TP53 signature. To assess whether the unexpected results were due to biological changes 12 PT-REC pairs were available from pts who received chemotherapy (CT) between PT & REC. CIN70 increased from PT to REC, DDRD (non-significantly) & PARPi7 decreased. 4/5 TP53 wildtype classified PT samples classified as mut in REC. The BRCA1/2 & DDRD-treatment interactions only held in pts who received CT before trial entry (table). The PARPi7-treatment interaction only held in CT naïve pts. In CT naïve pts, high CIN70 tumors suggested higher C RR as hypothesized. Restricted to the 149 PAM50 basal-like pts, results were non-significant but similar trends seen. Conclusions: In this trial of aTNBC, DDRD high pts with prior CT had better RR to D than C. A possible explanation for this unexpected result is selective pressure of adjuvant DNA damaging CT and selection for relative taxane sensitivity in those who recur despite a high DDRD score. The hypothesised CIN70 treatment interaction was observed in CT naïve pts. Our results suggest care is required in application of signatures to initial diagnostic material when predicting response to DNA damaging agents at REC particularly in pts with prior CT. [Table: see text]
The landscape of genomic alterations detected in serial circulating tumor DNA (ctDNA) in clinical progressive metastatic breast cancer.
Authors: Jacob Saya , Davis Andrew A. , Gerratana Lorenzo , Shah Ami N. , Katam Neelima , Zhang Qiang , Wehbe Firas , Flaum Lisa E. , Siziopikou Kalliopi P. , Platanias Leonidas C. , Gradishar William John , Behdad Amir , Cristofanilli Massimo 
Published: May 2020

1084 Background: Metastatic breast cancer (MBC) is associated with genomic evolution, representing a challenge at clinical progression. While tissue and blood next-generation sequencing (NGS) allows for the baseline detection of alterations, non-invasive longitudinal assessment of ctDNA can provide a tool for monitoring tumor evolution. We characterized genomic changes using serial ctDNA testing in patients with clinical progression. Methods: Patient data was obtained under an IRB-approved protocol and ctDNA was collected at Northwestern University between 2015-2019. All ctDNA samples were analyzed using the Guardant360 NGS assay. Of 255 patients with MBC, 86 had at least two serial ctDNA collections with the second collection drawn at first progression (P1) by imaging and clinical assessment. Participants were followed until second clinical progression (P2). We analyzed type of alterations, mutant allele frequency (MAF), number of alterations (NOA), and sites of disease on imaging in close proximity to ctDNA evaluation. Matched pairs variations in MAF and NOA at P1 and P2 were tested through Wilcoxon test. Results: We identified 44 HR+, 20 HER2+ and 22 TNBC cases. Median lines of therapy were 3 (interquartile range (IQR): 1-6) for HR+, 3 (IQR: 1-5) for HER2+, and 2 (IQR: 1-4) for TNBC. The most likely alterations between baseline to P1 were TP53 (p < 0.0075), PIK3CA (p < 0.0126), AR (p < 0.0126), FGFR1 (p < 0.0455) and ESR1 (p < 0.0143). In the HR+ subset , ESR1 was statistically more likely at P1. ESR1 at P1 was also associated with development of new liver lesions (p < 0.0320). ERBB2 mutation at P1 was associated with new lung (p < 0.0050) or bone lesions (p < 0.0030). Increase in NOA was observed between baseline and P1 (p < 0.0001), P1 and P2 (p < 0.0001), and baseline to P2 (p < 0.0004). MAF was increased between baseline and P2 (p < 0.0480). Conclusions: Serial ctDNA testing identified resistance alterations ( TP53, PIK3CA, AR, ESR1, FGFR1), with some mutations indicating new sites of disease ( ESR1, ERBB2). Heterogeneity of ctDNA was significantly associated with progressive disease. Prospective evaluation of the impact of serial ctDNA testing on treatment decisions is needed to expand the role of precision medicine in MBC. [Table: see text]
Outcomes for black versus white women with stage IV breast cancer enrolled on investigator-initiated clinical trials at Emory.
Authors: Ekpo Princess , Torres Mylin Ann , Rupji Manali , Switchenko Jeffrey M. , Subhedar Preeti , Gogineni Keerthi , Bhave Manali A. 
Published: May 2020

1086 Background: Black women are 40% more likely to die from their breast cancer compared to White women. Inadequate representation of Blacks in clinical trials may contribute to health care inequity. Emory’s Winship Cancer Institute (WCI) in Atlanta serves a significant Black population and has a unique opportunity to engage these underrepresented patients in clinical trials. We aimed to assess clinical outcomes in Black versus White women with metastatic breast cancer (MBC) enrolled on investigator-initiated clinical trials (IITs) at Emory. Methods: Black and White women with MBC enrolled on IITs conducted at WCI between 1/2009 and 1/2019 were retrospectively evaluated. Descriptive statistics were generated for all patient characteristics. Univariate analyses and a multiple logistic regression model were used to assess the effect of age and race on clinical response, length of time on trial, number of therapy lines prior to trial enrollment, and toxicity on trial. Overall survival was assessed using Kaplan Meier analysis. Results: Sixty-two women with MBC were included [White, n = 41 (66%), and Black, n = 21 (34%), p = 0.55]. Over 90% of women were enrolled on phase II clinical trials and received targeted therapy. Mean age at clinical trial consent was 53.2 and 55.9 years in Black and White women, respectively (p = 0.36). While the majority of women had hormone-receptor positive disease, a higher percentage of Blacks had triple negative breast cancer (29% vs. 17% in Whites, p = 0.39). Black women had fewer lines of systemic therapy prior to trial enrollment (2.86 vs. 4.3, respectively, p = 0.017) and were enrolled on trial for less time than White women (5.67 mo vs. 7.83 mo, respectively, p = 0.22). There were no differences in toxicity rates among patients enrolled on IITs based on race. Black women were more likely to have progressive disease (PD) on trial (45% in Blacks vs. 20% in Whites, p = 0.05). While there was no significant difference in overall survival (p = 0.482), there was a trend towards shorter survival in Black women (51.3 mos vs. 64 mos, respectively). Conclusions: Black women with MBC who enrolled on IIT trials at Emory had worse treatment response and a trend towards poorer survival compared to White women. More research is needed to determine whether this is due to adverse biology. These results reinforce the need for exploration of biomarkers of response by race and ethnicity and improved representation of Blacks in clinical trials to inform real world efficacy.
Surgery at primary and metastatic sites for stage IV breast cancer (BC): A National Cancer Database (NCDB) analysis.
Authors: Bilani Nadeem , Elson Leah , Elimimian Elizabeth Blessing , Liang Hong , Nahleh Zeina A. 
Published: May 2020

1099 Background: There is no clear evidence of a survival benefit of primary tumor resection in patients with stage IV breast cancer (BC). This large study evaluated factors associated with undergoing primary tumor resection, and whether resection at the primary site, or distant site resection (metastasectomy), was associated with better overall survival (OS). Methods: This retrospective analysis of stage IV BC cases used the 2004-2016 National Cancer Database (NCDB) population. To evaluate variables associated with primary tumor resection, we used univariate analyses (chi-squared and Wilcoxon rank-sum test), followed by multivariate logistic regression. Consequently, we conducted multivariate Cox regression survival analyses on the following groups: 1) all stage IV BC patients; 2) a subset of those with only 1 site of metastasis; and 3) another subset with metastasis to > 1 distant site. Results: A total of 54,871 stage IV BC patients were included in this analysis. From this, we analyzed a subset with only 1 distant site involved (n = 30,480) and another subset with multiple secondary sites (n = 17,344). In total, 15,661 patients underwent surgery at the primary site: 11,451 (73.1%) were non-Hispanic white; 2479 (15.8%) were non-Hispanic black; 981 (6.3%) were Hispanic and 484 (3.1%) were Asian. Variables associated with undergoing resection of the primary tumor were: age, race, Charlson/Deyo score, insurance and facility type, involved breast quadrant, receptor status, N-staging, extent of metastasis and year of diagnosis. Survival analysis of all stage IV patients showed that both lumpectomy (HR 0.59, 95% CI: 0.57-0.62, p < 0.0001) and mastectomy (HR 0.62, 95% CI: 0.60-0.64, p < 0.0001) were associated with better OS when compared to no surgery. The statistical effect was larger in the subgroup with metastasis to 1 site, but still significant in the subgroup with multiple metastatic sites. Distant site resection also yielded a survival benefit compared to no metastasectomy across all 3 groups. In the subgroup with metastasis to only 1 site, metastasectomy was associated with better OS when the metastatic site was liver (HR 0.60, 95% CI: 0.43-0.82, p = 0.0018), lung (HR 0.47, 95% CI: 0.37-0.61, p < 0.0001), and brain (HR 0.70, 95% CI: 0.55-0.88, p = 0.0022). Conclusions: Across all 3 patient subgroups, primary tumor resection (lumpectomy or mastectomy) and metastasectomy were associated with improved OS. Additional stratified analysis in the subgroup with only 1 metastatic site showed benefit of metastasectomy when that site was the lung, liver or brain.
Stress related to electronic health record (EHR) use among oncology trainees: A quality improvement study to optimize information gathering.
Authors: Ganta Teja 
Published: May 2020

11015 Background: Poor EHR usability is associated with physician burnout [1]. Oncology providers are tasked with coordinating data from multiple sources/tabs within an EHR (biomarkers, genetic data, imaging, etc.) to make treatment plan decisions. It is hypothesized that oncology trainees will have decreased stress using an EHR tool to optimize data gathering. Methods: This single-institution quality improvement study aims to decrease the time and stress associated with navigating the EHR to review/document laboratory data among first-year clinical oncology fellows rotating on consult services at The Mount Sinai Hospital as measured by self-reported survey data. An EHR tool was built that pulls into the note a drop-down list of user-selectable laboratory panels grouped according to hematologic/oncologic disease presentations. A survey was sent to all fellows in the program to assess attitudes toward the EHR. All 1st-year fellows were given access to the EHR tool as they are the ones who primarily rotate on consult services. After 3 months, a follow-up survey was sent to 1st-year clinical fellows to assess satisfaction with the EHR intervention. Results: For the baseline survey, there are a total of 17 respondents (response rate 77%). 70.6% of fellows believe using the EHR increases their level of stress. The most prevalent reasons cited for frustrations with the EHR are “Hard to read other providers’ notes” (82.4%), “Gathering information from multiple different pages” (76.5%), “Increased documentation requirements” (76.5%), “Inability to quickly navigate the system” (64.7%). For the follow-up survey targeting 1st-year fellows, there are a total of 6 respondents (response rate 100%). 5 fellows tried the EHR tool at least once. Of those 5 fellows, 100% use it daily in clinical practice while on consult services, believe it makes notes more legible, believe it saves time spent in chart review, and believe it decreases their stress associated with navigating the EHR. Conclusions: A majority of clinical oncology fellows believe that the EHR contributes to their stress. The reasons cited suggest that interventions that optimize note-writing and chart-reviewing may decrease stress. The majority of fellows who used this EHR tool believe the tool improved their efficiency and stress levels. This suggests more widespread use of this tool among oncology clinicians may contribute to wellness although further studies to increase utilization must be taken.
A single-arm multicenter phase II trial of doxorubicin (Doxo) in combination with trabectedin (Trab) given as first-line treatment to patients with metastatic/advanced uterine (U-LMS) and soft tissue leiomyosarcoma (ST-LMS): Final results of the LMS-02 study.
Authors: Pautier Patricia , Floquet Anne , Chevreau Christine , Penel Nicolas , Guillemet Cecile , Delcambre Corinne , Cupissol Didier , Selle Frederic , Isambert Nicolas , Piperno-Neumann Sophie , Saada-Bouzid Esma , Bertucci Francois , Bompas Emmanuelle , Boudou-Rouquette Pascaline , Collard Olivier , Le Brun Ly Valérie , Toulmonde Maud , Le Cesne Axel , Lacas Benjamin , Duffaud Florence 
Published: May 2020

11506 Background: U-LMS and ST-LMS are rare tumors with poor prognosis when locally advanced or metastatic, and with moderate chemosensitivity. Overall response rates (ORR) given in the 1st-line setting do not exceed 50% for U-LMS and 35% for ST-LMS with a mean response duration of 3- 6 months without impact on overall survival (OS). In 2015 we reported very encouraging results of the LMS-02 study (NCT02131480) with ORR of 59.6% in U-LMS, and 39.3% in ST-LMS with manageable toxicity (Pautier; Lancet oncol 2015). Herein, we report the updated results of progression-free survival (PFS) and final results of overall survival (OS). Methods: Patients (pts) received 60 mg/m² intravenous Doxo followed by trabectedin 1.1 mg/m2 as a 3-hour infusion on Day 1 and pegfilgrastim on Day 2, repeated every 3 weeks for up to 6 cycles. Surgery for residual disease was permitted. Patients were stratified into U-LMS and ST-LMS groups. Results: Overall, 108 patients with LMS with a median age of 59 years and mostly metastatic disease (85%) were enrolled. Of those, 77 patients (71.3%) have received all 6 cycles of treatment, and 20 patients (18.5%) had metastasis resection. With a median follow-up of 7.2 years (95% CI: 6.9 - 8.2), the overall median PFS was 10.1 months (95% CI: 8.5 - 12.6), being 8.3 months (95 CI: 7.4 - 10.3) and 12.9 months (95% CI: 9.2 - 14.1) in U and ST group, respectively. Median OS was 34.4 months (95% CI: 26.9 - 42.7), being 27.5 months (95% CI: 17.9 - 38.2) in U-LMS and 38.7 months (95% CI: 31.0 - 52.9) in ST-LMS group. The median OS among the 20 pts with surgery was not reached vs 31.6 months in the population without surgery (95% IC: 23.9 - 35.4). Conclusions: The Doxo +Trab combination is an effective 1st-line therapy for pts with LMS, with promising PFS and OS results and an acceptable safety profile. Merely for comparison, the most recent results of Doxo alone in metastatic LMS, given in 1st-line setting in a phase III ANNOUNCE trial conducted during the same period, reported median PFS of 6.9 months, and median OS of 21.9 months (ASCO 2019 LBA3). Results of the LMS04 trial (NCT02997358), a randomized phase III study comparing this combination vs Doxo alone in 1st-line therapy in metastatic LMS are pending. Clinical trial information: NCT02131480 .
A phase II study of MEK162 (binimetinib [BINI]) in combination with imatinib in patients with untreated advanced gastrointestinal stromal tumor (GIST).
Authors: Chi Ping , Qin Li-Xuan , Kelly Ciara Marie , D'Angelo Sandra P. , Dickson Mark Andrew , Gounder Mrinal M. , Keohan Mary Louise , Movva Sujana , Nacev Benjamin , Crago Aimee Marie , Yoon Sam S. , Ulaner Gary A. , Martindale Moriah , Condy Mercedes M. , Phelan Haley , Biniakewitz Matthew , Singer Samuel , Hwang Sinchun , Antonescu Cristina R. , Tap William D. 
Published: May 2020

11508 Background: ETV1 and KIT are lineage-specific master transcriptional and signaling survival factors in GIST. In preclinical models, dual lineage targeting of ETV1 by MEK inhibition with BINI and KIT by imatinib are synergistic in suppressing GIST tumorigenesis and progression. This single-arm phase II study is designed to test the efficacy of the BINI+imatinib as a first-line treatment in patients (pts) with advanced GIST. Methods: Adult pts with untreated advanced GIST received imatinib (400mg daily) plus BINI (30mg twice daily), 28-day cycles. The primary endpoint (EP) was RECIST1.1 objective response rate (ORR) (complete response [CR]+partial response [PR]). The study was designed to detect a 20% improvement in the ORR of imatinib alone (unacceptable rate of 45%; acceptable rate of 65%). A sample size of 44 patients was required, using an exact binomial test, one-sided type I error of 0.08 and type II error of 0.1. Confirmed PR in > 24 pts would be considered positive. Secondary EPs included RR by Choi and EORTC criteria, resectability conversion rate (RCR), progression free survival (PFS), overall survival (OS) and long-term AEs. Correlatives included characterization of tumor genomics by MSK-IMPACT, cfDNA by MSK-ACCESS, ETV1 protein levels and transcriptomes and signaling inhibition. Results: At data cutoff of Jan 31, 2020, 38/39 pts with advanced GIST of all genotypes, including 3 KIT/PDGFRA-wild type GIST pts, were evaluable for primary EP. Median age 60 (range 29-78), 29% female. 26/38 pts with confirmed PR; Best ORR was 68.4% (two-sided 95% CI, 51-83%; one-sided 90% CI, 57-100%). 8/9 pts became resectable after treatment; RCR was 88.9% (95% CI, 52-100%). 13 pts remain on trial (2-159 weeks [wks]). 9 pts discontinued trial due to disease progression (11-159 wks); one pt progressed within 3 months, indicating primary resistance. Grade 3/4 toxicity included CPK elevation (asymptomatic, 61%), neutrophil decrease (11%), maculopapular rash (8%), anemia (8%). No unexpected toxicities observed. Correlation of outcome with MSK-IMPACT, MSK-Access and paired tumor biopsies will be presented. Conclusions: This study met its primary endpoint. BINI plus imatinib is highly effective in treatment-naive advanced GIST, with expected and manageable long-term treatment-associated toxicities. The combination strategy warrants further evaluation in direct comparison with imatinib in the frontline treatment of GIST. Clinical trial information: NCT01991379 .
A multicenter phase II study of nivolumab +/- ipilimumab for patients with metastatic sarcoma (Alliance A091401): Results of expansion cohorts.
Authors: Chen James Lin , Mahoney Michelle R. , George Suzanne , Antonescu Cristina R. , Liebner David A. , Van Tine Brian Andrew , Milhem Mohammed M. , Tap William D. , Streicher Howard , Schwartz Gary K. , D'Angelo Sandra P. 
Published: May 2020

11511 Background: In the open-label multicenter phase II study, A091401, nivolumab (N) and nivolumab+ipilimumab (N+I) demonstrated a confirmed response rate (RR) of 5% and 16%, respectively in patients (pts) with advanced sarcoma (D’Angelo SP et al Lancet Oncology 2018). Responses occurred in undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma, leiomyosarcoma, sarcoma not otherwise specified and alveolar soft part sarcoma. Here, we report efficacy of N and N+I, in each of 3 expansion cohorts [gastrointestinal stromal tumor (GIST), UPS and dedifferentiated liposarcoma (DDLS)]. Methods: Pts refractory to ≥ 1 regimen(s) were randomized (non-comparative) to receive either N [N (3 mg/kg q2W)] or N+I [N (3 mg/kg Q3W x4, then Q2W) plus I (3 mg/kg q3W x4)]. The primary endpoint was 6 month confirmed RR (RECIST v1.1). For UPS and DDLS, 2 confirmed responses in the 1st 12 evaluable pts was needed (85% power, 1-sided alpha=0.15, 5 v 25% RR). For GIST, a confirmed response in the 1st 9 evaluable pts expanded enrollment to 24 (80% power, 1-sided alpha=0.10, 5 v 20% RR). Other endpoints: adverse events (AEs, TRAEs), progression-free and overall survival (PFS, OS), and correlatives. Results: See table. Clinical trial information: NCT02500797 . Conclusions: Neither N or N+I lead to confirmed responses in GIST. In DDLS and UPS, the primary response endpoint was met with N+I but not with N alone (RR 14% for N+I vs. 7% and 8% for N alone). For the GIST cohort TRAE was higher with N+I, holding enrollment as required per protocol. There remains a pressing need to determine genomic and clinical biomarkers of response, resistance and toxicity. Correlative analyses (whole exome sequencing, multiplex IHC and RNAseq) are in progress. Support: U10CA180821, U10CA180882; ClinicalTrials.gov Identifier: NCT02500797. [Table: see text]