bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overall survival and updated progression-free survival results from a randomized phase 2 trial comparing the combination of olaparib and cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer.
Authors: Liu Joyce F. , Barry William Thomas , Birrer Michael J. , Lee Jung-min , Buckanovich Ronald J. , Fleming Gini F. , Rimel Bj , Buss Mary K. , Nattam Sreenivasa R. , Hurteau Jean , Luo Weixiu , Farooq Sarah , Whalen Christin , Kohn Elise C. , Ivy S. Percy , Matulonis Ursula A. 
Published: September 2018

5535 Background: We previously reported that the combination of cediranib (ced) and olaparib (olap) improved progression-free survival (PFS) and overall response rates (ORR) in women with recurrent platinum-sensitive (plat-sens) high-grade serous (HGS) or BRCA-related ovarian cancer (OvCa) (NCT 01116648). We conducted an updated PFS and overall survival (OS) analysis. Methods: Patients (pts) across 9 centers were randomized 1:1 in this Ph 2 open label study to Olap (olap 400 mg capsules BID) or Ced/Olap (olap 200 mg capsules BID; ced 30 mg daily), stratified by BRCA status and prior anti-angiogenic therapy. Eligibility included pts with recurrent plat-sens HGS or BRCA-related OvCa. Pts had measurable disease by RECIST 1.1, PS 0 or 1, and the ability to take POs. No prior anti-angiogenics in the recurrent setting or prior PARP inhibitor was allowed. PFS was defined as time from randomization to radiographic progression or death. OS was defined as time from randomization to death. Results: Pts were enrolled from Oct 2011 to Jun 2013: 46 to Olap, 44 to Ced/Olap. 48 pts were known BRCA carriers (25 Olap; 23 Ced/Olap). As of Dec 21, 2016, 67 pts had a PFS event, and 52 pts had an OS event. Updated median PFS was 8.2 mos for Olap and 16.5 mos for Ced/Olap (HR 0.50, 95% CI 0.30-0.83, p=0.007). Median OS was 33.3 mos for Olap and 44.2 mos for Ced/Olap (HR 0.64, 95% CI 0.36-1.11, p=0.11). Within known germline BRCA mut carriers, updated PFS was 16.5 vs 16.4 mos (HR 0.75, p=0.42), and OS was 40.1 vs 44.2 mos (HR 0.79, p=0.55) for Olap and Ced/Olap, respectively. In pts without known germline BRCA mut, updated PFS was 5.7 vs 23.7 mos (HR 0.32, p=0.002), and OS was 23.0 vs 37.8 mos (HR 0.48, p=0.074). Conclusions: Updated PFS results consistently demonstrated that Ced/Olap significantly extended PFS compared to Olap in the overall population of women with plat-sens OvCa. In this Phase 2 study not powered to detect OS diferences, there was a trend towards OS improvement with Ced/Olap, particularly in pts without a known germline BRCA mutation. Results from ongoing studies of this oral combination in OvCa are of clinical interest. Clinical trial information: NCT 01116648.
Somatic mutations in homologous recombination pathway genes in ovarian cancer.
Authors: Aghajanian Carol , DeLair Deborah , Grisham Rachel N. , Hensley Martee Leigh , Konner Jason A. , Makker Vicky , O'Cearbhaill Roisin Eilish , Sabbatini Paul , Soumerai Tara , Snyder Charen Alexandra , Spriggs David R. , Soslow Robert A. , Tew William P. , Zamarin Dmitriy , Robson Mark E. , Berger Michael F. , Solit David B. , Hyman David Michael , Cadoo Karen Anne 
Published: September 2018

5545 Background: 15% of patients with OC have a germline BRCA 1 / 2 mut & 6% of OC have a somatic BRCA 1/ 2 mut. Inhibitors of poly ADP ribose polymerase (PARPi) are approved in this setting. Data is evolving as to activity of PARPi in BRCA wild type OC with somatic homologous recombination (HR) gene deficiency. We sought to determine the prevalence of somatic alterations in HR genes in an unselected cohort of epithelial OC of any histologic type. Methods: From 03/2014-10/2016 patients consented to an IRB approved protocol for tumor-normal sequencing, via a custom next-generation sequencing panel (MSK-IMPACT) with return of results for tumor mut only. Muts in 14 HR genes ( ATM, BARD1, BRCA1, BRCA2, BRIP1, CHEK1, CHEK2, FANCA, MRE11, NBN, PALB2, PTEN, RAD51D, RAD51C) and p53were assessed. Statistics were analyzed using GraphPad Prism v. 6. Results: 260 tumors were sequenced; 156 (60%) high grade serous (HGS), 34 (13%) low grade serous (LGS), 34 (13%) clear cell, 10 (4%) mucinous, 8 (3%) endometrioid, 18 (7%) mixed/other histology. 151 (97%) of HGS and 24 (23%) of the remaining tumors harbored p53 mut. 48 (18%) somatic HR mut were identified. (Table 1) 26 HGS (17%) tumors and 22 (21%) of the remaining tumors harbored a HR gene mut (HGS vs other histology, p=0.4). Notably, 8 (24%) of clear cell cancers demonstrated HR gene muts (vs HGS, p=0.3). 18 (38%) of the identified muts in the overall cohort were in BRCA 1/2. There were no somatic HR gene muts identified in the mucinous OC, which were characterized by frequent p53 (90%) and KRAS(60%) muts. Conclusions: In this cohort of OC, 17% of tumors harbor somatic HR gene muts. The prevalence of HR somatic muts was similar in HGS vs other histologies, with the exception of mucinous OC. BRCA1/2 muts predominated, however 60% of identified muts were in other genes. Accrual is ongoing to increase histologic cohort sizes. Broad HR gene somatic mutational profiling may identify a wider cohort of OC patients with potential to benefit from PARPi therapy. [Table: see text]
Shared decision-making in ovarian cancer.
Authors: Wenzel Lari B. , Mukamel Dana B , Osann Kathryn , Sparks Lisa , Havrilesky Laura Jean , Wright Alexi A. , Walker Joan L. , Robison Katina , Alvarez Ronald David , Van Le Linda , Wakabayashi Mark Tsuneo , Randall Leslie M. , Wahi Aditi , Hsieh Susie , Lipscomb Joseph , Cohn David E. 
Published: September 2018

5549 Background: The value of shared decision-making in ovarian cancer is relatively unexplored. The goal of this study was to test a new decision aid, Patient Centered Outcome Aid (PCOA), that facilitates shared decision-making and helps ovarian cancer patients assimilate information and identify quality of life (QOL), toxicity and survival trade-offs between IP/IV therapy and IV therapy alone, based on their preferences and personal clinical characteristics. Methods: Participants were randomized to either PCOA (N=64) or usual care (N=59). Patient characteristics, QOL and shared decision-making data were collected at baseline and treatment initiation. Primary outcomes included satisfaction with treatment decision and decisional regret. Comparisons were made using t-tests and multivariate methods, adjusting for patient covariates. Multivariate linear models were used to investigate predictors of the primary outcomes. Results: Although satisfaction and decisional regret did not differ significantly by arm at any time point, the majority of PCOA patients indicated that the aid helped them understand treatment options and side effects. Notably, low shared decision-making and low QOL, were significant predictors of low satisfaction at treatment initiation (multiple r=0.76), six months (multiple r=0.48) and nine months (r=0.58). They were also significant predictors of decisional regret (multiple r=0.48 and 0.36 at 6 and 9 months). Patient covariates including age, stage, treatment and neoadjuvant status were not associated with differences in satisfaction or decisional regret. Conclusions: There were no clinically meaningful differences in satisfaction with the treatment decision, or decisional regret between the study arms. The absence of a difference may reflect the high degree of shared decision-making in both arms and greater disease severity in PCOA patients, who were more likely to report low baseline QOL and declining QOL over time. Both shared decision-making and quality of life were robust, independent predictors of satisfaction with the treatment decision over time. This implies that women who perceive themselves as less engaged in the decision process, and report poor QOL may benefit from a decision aid, in addition to physician counseling. Clinical trial information: NCT02259699.
Bevacizumab, eribulin, and oxaliplatin in patients with platinum-resistant ovarian carcinomas: A phase II study with biomarker analysis.
Authors: Takano Masashi , Kouta Hiroko , Kudoh Kazuya , Kita Tsunekazu , Yoshikawa Tomoyuki , Kikuchi Ryoko , Matsuura Hiroko , Miyamoto Morikazu , Goto Tomoko , Furuya Kenichi , Kikuchi Yoshihiro 
Published: September 2018

5550 Background: Eribulin is a candidate for paclitaxel-refractory breast cancers, and Bevacizumab (B) is known to enhance efficacy of anti-cancer agents in ovarian cancers. A phase II study to evaluate weekly administration of B with eribulin and oxaliplatin (EriOX) in patients with platinum-resistant and refractory ovarian carcinomas (PR-ROC) was performed. Methods: Eligible patients were as follows: (a) ECOG PS = 0~2 (b) histologically confirmed epithelial ovarian cancer (c) diagnosed as platinum-resistant ovarian cancer (d) written informed consent. Patients were treated with weekly-B-EriOX consisting of B (2mg/kg), eribulin (1mg/m2) and oxaliplatin (30mg/m2), three weeks on and on week off, q4weeks. The study was conducted using two-stage design of Simon (type I error = 0.05, power = 0.9, true response rate = 25%). Biomarker analyses including serum VEGF, BNP, p53, IL-6, and Her-2 were also conducted. Results: A total of 34 patients were enrolled in the present study: 13 cases in the first-stage, and additional 21 cases in the second-stage. There were 3 responders (≧2) in the first-stage, and the protocol was proceeded to the second-stage. Median age of the patient was 58.5 years (range: 35-76), and median number of previous regimen was 4 (range: 2-9). Overall, two patients (6%) had a complete response (CR), 8 patients (24%) had a partial remission (PR) and 16 patients (47%) had a stable disease (SD). The response rate and clinical benefit rate (CR+PR+SD) were 29% and 76%, respectively. Median progression-free survival was 4 months (range: 1-27+). Hematological adverse effects (AE) with grade 3/4 were observed in 4 patients (11%). Non-hematological AE greater than grade2 was observed in one case: hypo albuminemia and edema, which were manageable and tolerable. As there were 10 responders (≧6), the protocol was considered for additional investigation. The Patients with elevated serum mutated p53 / IL-6 showed lower response and worse prognoses. Conclusions: Weekly B and EriOX administration was considered for additional investigation for patients with PR-ROC. Serum mutated p53 protein and/or IL-6 could be biomarkers in PR-ROC patients treated with weekly B and EriOX.
Panitumumab in platinum-sensitive epithelial ovarian cancer patients with KRAS wild-type: The PROVE-study, a phase II randomized multicenter study of the North-Eastern German Society of Gynaecologic Oncology.
Authors: Chekerov Radoslav , Klare Peter , Krabisch Petra , Potenberg Jochem , Heinrich Georg , Mueller Lothar , Kurbacher Christian M. , Grischke Eva-Maria , Braicu Elena Ioana , Wimberger Pauline , Sehouli Jalid 
Published: September 2018

5558 Background: For ovarian cancer (OC) patients with platinum-sensitive recurrence the addition of new biologic agents to chemotherapy may improve survival. Panitumumab is a fully human monoclonal antibody specific to the epidermal growth factor receptor (EGFR). The purpose of this trial was to investigate the therapeutic efficacy of panitumumab in the combination with carboplatin-based chemotherapy in relation to the respective standard combination in patients with a KRAS wildtype with platinum-sensitive recurrent ovarian cancer (NCT01388621). Methods: Major eligibility criteria were pretreated platinum-sensitive epithelial ovarian/ fallopian/ peritoneal cancer and no more than 2 prior treatments for this disease. Only patients with measurable disease or elevated CA125 and with KRAS wild type were eligible. Patients were treated with Carboplatin AUC4/Gemcitabine 1000 mg/m² or Carboplatin AUC5/PLD 40 mg/m² and randomized to panitumumab 6 mg/kg day 1 and day 15, every 3 or 4 weeks. Tumor assessment was performed at baseline and at every third cycle according to CT-scan and CA-125 criteria. Results: In this multi-institutional phase II trial 102 patients were randomized and 96 enrolled for the final analysis. Progression-free survival in the intention-to-treat population (N=96) was 9.5 vs. 10.7 months (HR 0.829, 95%CI of 8.5-11.6 months vs 8.5-13.1 months) for the experimental vs. standard arm, p=0.45. Data of overall survival are not jet evaluable. The most common treatment related grade 3+ toxicities included hematologic toxicity (54%), skin reactions (18%) and gastrointestinal events (16%). Conclusions: The addition of panitumumab to platinum-based chemotherapy for recurrent ovarian cancer does not influence efficacy and progression-free survival in platinum sensitive patients, while no new additional toxicity aspects for panitumumab were evaluated. Clinical trial information: NCT01388621.
ENGAGE: Evaluation of a streamlined oncologist-led BRCA mutation (BRCAm) testing and counselling model for patients with ovarian cancer.
Authors: Colombo Nicoletta , Scambia Giovanni , Chalas Eva , Huang Gloria S. , Pignata Sandro , Fiorica James , Van Le Linda , Ghamande Sharad A. , Gonzalez Santiago Santiago , Bover Isabel , Suárez Begoña Graña , Green Andrew Emmons , Huot-Marchand Philippe , Bourhis Yann , Karve Sudeep , Blakeley Christopher 
Published: September 2018

5559 Background: Short BRCAm testing turnaround times (TAT) are crucial to making timely treatment decisions for patients (pts) with ovarian cancer. ENGAGE (NCT02406235; D0816R00006) evaluated a streamlined, oncologist-led germline BRCAm testing model, piloted by the Institute of Cancer Research and the Royal Marsden Hospital, London, UK. Results presented are from the final analysis (data cut-off: 30 Sep 2016). Methods: This prospective, observational study enrolled pts with ovarian cancer across sites in the US (n = 11), Italy (n = 8) and Spain (n = 7). Oncologists and nurses at participating sites were trained on genetic counselling techniques relating to BRCAm testing. Primary endpoints were BRCAm testing TAT (time from initial counselling to the provision of test results or post- BRCAm test counselling [whichever occurred latest]); pts’ satisfaction with the oncogenetic testing model, evaluated using pre- and post- BRCAm testing surveys; and clinicians’ opinion on the value of this new testing pathway, evaluated using a post- BRCAm testing survey. Results: For the 700 evaluable pts enrolled (US = 317; EU = 383), pre- BRCAm testing counselling was carried out by either an oncologist (40.7%) or clinical staff (nurse or research coordinator; 59.3%) in the US, and only by oncologists in the EU. The median overall TAT was 9.1 weeks (all pts), with 12.0 weeks in Spain, 20.4 weeks in Italy (17.4 weeks EU median) and 4.1 weeks in the US. The differences were mainly due to the time from BRCAm testing to obtaining the test results. Satisfaction with the overall counselling was high amongst pts, with a mean dimension score rating of 3.8/4 (where 4.0 = highest satisfaction). 93.6% of pts were happy to have received genetic testing as part of an existing oncologist appointment, and more than 80% of oncologists were satisfied with the screening process, agreeing that it was an efficient use of their time. Conclusions: The ENGAGE study results show that a streamlined oncologist-led BRCAm testing model can offer reduced TAT and high levels of satisfaction amongst pts and clinicians. The success of this model is enhanced by access to a BRCAm testing facility, from which results can be obtained quickly. Clinical trial information: NCT02406235; D0816R00006.
Ki67 as a prognostic factor in low grade serous ovarian cancer (LGSOC): A retrospective analysis of the Tumor Bank Ovarian Cancer (TOC).
Authors: Sehouli Jalid , Plett Helmut , Richter Rolf , Denkert Carsten , Darb-Esfahani Silvia , Chekerov Radoslav , Schmitt Wolfgang D , Grabowski J.P. , Taube Eliane T , Braicu Elena Ioana 
Published: September 2018

5562 Background: LGSOC is a rare and distinct entity characterized by younger age, lower response to chemotherapy and better clinical outcome. Aim of this study was to evaluate the impact of Ki67, estrogen and progesterone receptors (ER and PR) on platinum response and survival in primary LGSOC patients. Methods: 80 primary LGSOC patients with available FFPEs were identified within TOC. The histology was confirmed at a second histological evaluation. For Ki67 analysis conventional immunohistochemical staining was performed with the Mib-1 clone on Ventana. Slides were explored with a light microscope camera. A representative field for Ki-67 evaluation was selected, in case of heterogeneous staining a hot spot was chosen. The software classified detected cells into non-tumor, negative and positive cells. When necessary, a correction of tumor and non-tumor areas was performed by an experienced pathologist. The counted cells ranged between 175 and 2398. Overall the method allows a precise, continuous and standardized means to quantify Ki-67. ER and PR status was determined on scanned IHC TMA slides. ER and PR positive tumors were defined if the percentage of stained tumor cells was at least 10%. Statistical analysis was performed using IBM SPSS Statistics. Results: Median age at diagnosis was 56 years (range: 20-81), 81.3% of patients presented in advanced stage and 96.3% received platinum based chemotherapy. Ki67 median value was 5.09 (IQR: 1.56-10.5). 93.1% and 47.9% of the patients showed ER and PR positive tumors, respectively. Median overall survival (OS) was 45.5 months (range: 0.1-182.8). Our analysis showed that platinum free interval (PFI) was significant longer in patients with lower Ki67 (p = 0.006). Higher proliferation rates were significant associated with poorer progression free (p = 0.011, HR = 1.039, 95%CI: 1.009-1.070) and OS rates (p = 0.001, HR = 1.059, 95%CI: 1.025-1.095). No differences in clinical outcome were seen in patients with different ER and PR status. Conclusions: This is the first study showing that higher Ki67 values correlate with shorter PFI and poorer survival rates in LGSOC, underlying the heterogeneous character of this disease.
Are symptoms of ovarian cancer evident: A retrospective analysis of claims data to determine prior symptoms to diagnosis.
Authors: Langabeer Denise Manon , Ganduglia Cazaban Cecilia , Swartz Michael D , Krause Trudy 
Published: September 2018

5565 Background: There are no standard of care screening methods for ovarian cancer. Over sixty percent (60%) of ovarian cancer cases are found at Stage III and IV, which ultimately impacts a woman’s survival rate. The purpose of this study is to determine if specific symptoms are evident prior to diagnosis of ovarian cancer. Methods: A retrospective analysis of health insurance claims between 2008 through 2013 from a commercial payer was performed based on the following eligibility criteria: 1) women diagnosed with ovarian cancer, 2) at the time of diagnosis, 24 years of age or older, 3) enrolled in healthcare plan for a period of 24 months or more prior to diagnosis, and 4) resident in the state of Texas. Symptoms were identified based on ICD-9 diagnosis codes and categorized specific to pain, abdominal and pelvis, digestive, and bladder and were evaluated at minimum of six months prior to diagnosis. ICD9 codes are used for this analysis as the data is limited to years before the change to ICD10. Results: Baseline data of 3,641 women diagnosed with ovarian cancer were identified and were associated with 927,528 claims specific to the symptoms. The age of women diagnosed with cancer ranged between 24 and 88 (mean=52; SD: 0.1833). Nearly 70% of women were treated for one or more symptoms prior to diagnosis. The symptoms women experienced the most were associated with abdomen and pelvis at 60%. Pain, digestive, and bladder ranged between 20% and 30%. Conclusions: This research is intended to further explore whether symptoms are evident in women diagnosed with this disease, and if so, how long and how frequent did the symptoms occur prior to diagnosis. Additionally, a review of combination of symptoms is explored. This research is intended to provide a better understanding of the disease as well as support that women may need to be referred to an oncologist earlier for further evaluation should reoccurring symptoms present.
Evaluating the repertoire of immune checkpoint markers expressed on peripheral and ascites CD8+ T cells in ovarian cancer.
Authors: Gaillard Stephanie , Dumbauld Chelsae , Bilewski Alyssa , Ehrisman Jessie A , Secord Angeles Alvarez , Havrilesky Laura Jean , Berchuck Andrew , Weinhold Kent , Chan Cliburn , Yi John 
Published: September 2018

5571 Background: Understanding the immune checkpoint marker repertoire can facilitate development of therapeutic strategies to improve efficacy of immune-based therapies. We used a novel high-dimensional flow cytometry panel to determine co-expression patterns of immune checkpoint markers and effector function of CD8+ T cells from peripheral blood and ascites of patients newly diagnosed with ovarian cancer. Methods: Peripheral blood and ascites samples were collected from patients with epithelial ovarian cancer (n=8). Cells isolated from peripheral blood and ascites were used for immune profiling by multiparameter flow cytometry of 5 inhibitory receptors (PD-1, LAG-3, TIM-3, TIGIT, and BTLA) on CD8+ T cells, along with 4 functional parameters (production of each of the following: TNF-α, IFN-γ, IL-2, and upregulation of CD107a). A complementary multiplex analysis on plasma and ascites fluid was performed to quantify 14 soluble checkpoint markers. Results: The concentrations of soluble PD-1, TIM-3, LAG-3, CTLA-4, BTLA, IDO, and CD137 were increased in ascites fluid compared to plasma from patients with ovarian cancer. Ascites CD8+ T cells co-express higher levels of inhibitory receptors than peripheral CD8+ T cells. In total, CD8+ T cells in ascites retained the ability to produce effector functions at levels similar to peripheral blood. However, IFN-γ production was retained in PD-1 only expressing CD8+ T cells and decreased in CD8+ T cells co-expressing multiple receptors. Conclusions: High-dimensional flow cytometry allowed for the phenotypic and functional characterization of CD8+ T cells from ovarian cancer patients. The profile of receptor co-expression was distinct in peripheral blood compared to ascites. Collectively, our study suggests that co-expression of factors beyond PD-1 influences CD8+ T cell activity. Thus blocking PD-1 and PD-L1 alone may not be sufficient for CD8+ T cells expressing multiple inhibitory receptors.