bluuebunny/crossref_metadata_2025_split huggingface dataset:
Camrelizumab plus apatinib in patients with advanced cervical cancer: A multicenter, open-label, single-arm, phase II trial.
Authors: Lan Chunyan , Huang Xin , Shen Jing-Xian , Wang Yin , Xiong Ying , Li Jundong , Cao Xinping , Deng Yanhong , He Mian , Zou Guorong , Wang Xiaodi 
Published: May 2020

6021 Background: Camrelizumab is a fully humanized, monoclonal antibody against PD-1. We aimed to assess the efficacy and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor targeting VEGFR2, in patients with advanced cervical cancer. Methods: In this open-label, single-arm, phase 2 study done at four centres in China, eligible patients were aged 18–70 years, had an ECOG performance status of 0 or 1, progressed after at least one line of systemic chemotherapy for metastatic, recurrent or persistent cervical cancer, and had measurable disease. Patients received camrelizumab 200 mg every 2 weeks and apatinib 250 mg once daily. Treatment continued until disease progression, unacceptable toxicity, and withdrawal of consent. The primary endpoint was the objective response rate (ORR) assessed by RECIST version 1.1. An optimal Simon two-stage design was employed to test the null hypothesis of a 17% ORR versus 35% alternative (1-sided alpha 0.10, 80% power), if > 3 responses out of the first 16 patients were observed, then the study would continue to enroll a total of 44 patients. Results: Between Jan 21st, 2019, and Aug 1st, 2019, 45 patients were enrolled and received study treatment (safety population). The median age was 51 (range, 33–67) years. Median previous treatment lines were 2 (range, 1–4). As of Jan 22, 2020, median follow-up was 9.2 months (range, 2.4–12.2). 25 (59.5%; 95%: CI 44.7–74.4) of 42 patients who had at least one post-baseline tumor assessment (efficacy evaluable population) achieved an objective response, including two (4.8%) complete response, and 23 (54.8%) partial response. Median duration of response was not reached. The disease control rate was 88.1% (37/42). Median progression-free survival (PFS) was 7.6 months (95% CI: 5.8–not reached). 31 (68.9%) patients had grade ≥ 3 treatment-related adverse events (TRAEs). Grade ≥ 3 TRAEs occurring in ≥ 5% of patients were hypertension (24.4%), anemia (20.0%), fatigue (15.6%), γ-glutamyltransferase increased (13.3%), neutropenia (6.7%), and thrombocytopenia (6.7%). In post-hoc analyses, objective response was noted in 20 (69%) of 29 patients with PD-L1-positive tumors, and in 5 (50.0%) of 10 patients with PD-L1-negative tumors (Chi-square test, P = 0.281). PFS was longer in patients with PD-L1-positive tumors than patients with PD-L1-negative tumors (median PFS: 9.6 versus 5.3 months; log-rank test, P = 0.017). Conclusions: Camrelizumab plus apatinib showed promising antitumor activity and tolerable toxicities in patients with advanced cervical cancer. Clinical trial information: NCT03816553.
Phase II trial of guadecitabine priming and pembrolizumab in platinum resistant recurrent ovarian cancer.
Authors: Matei Daniela , Pant Alok , Moroney John William , Fleming Gini F. , Tanner Edward , Swetzig Wendy M , Xu Jiahui , Cardenas Horacio , Kandpal Manoj , Gavrilescu Andreea , Chen Siqi , Kocherginsky Masha , Davuluri Ramana V , Zhang Bin 
Published: May 2020

6025 Background: Platinum resistant ovarian cancer (PROC) remains a disease of high need. Immune checkpoint inhibitors (ICI) have modest activity. We hypothesized that priming with a hypomethylating agent (HMA) guadecitabine (G) will improve the anti-tumor activity of ICI in PROC by enhancing tumor cell recognition by CD8+ T cells. Methods: This open-label phase II study used a Simon’s two-stage design. Eligible patients (pts) had recurrent PROC; ECOG PS of 0-1; normal end organ function; and measurable disease. Up to 5 prior cytotoxic regimens were allowed. Treatment consisted of G 30mg/m2 sq D1-4 and pembrolizumab (P) 200mg iv D5. Each cycle was 21 days. The primary endpoint was response rate (RR). Secondary endpoints were progression-free survival (PFS), clinical benefit rate (CBR), and toxicity assessment. Translational endpoints were LINE1 methylation in PBMCs, global tumor methylation, and immune endpoints. Tumor biopsies were obtained at baseline and after 2 cycles. If 2 patients experienced clinical benefit in stage I [n = 16], enrollment proceeded to stage II. The null hypothesis was rejected for ≥ 6 responses in 35 evaluable patients. Results: 48 pts were enrolled, 43 were treated, and 33 were evaluable for response. Histology was serous (35), endometrioid (2), clear cell (3) and other (3). Median age was 63 (range 40-88) and median number of prior regimens was 4 [range 1-8]. Two PRs were recorded in the first stage, allowing second stage of enrollment. Overall, there were 2 PRs (RR = 6.6%) and 16 pts had stable disease (SD) [48%]. The clinical benefit rate (PR + SD > 3 months) was 27%. One patient continued treatment for > 2 yrs. Grade 3-4 related toxicities were neutropenia [20], lymphopenia, (9), anemia (2), neutropenic fever (1), rash (1), and others (8). There were 13 grade 3-4 SAEs and 4 grade 5 SAEs, assessed as being unrelated to treatment. LINE1 was hypomethylated in PBMCs D5 vs. D1 (n = 21, p = 0.001). Epic arrays measured global tumor methylation, with 39579 CpG sites (0.05%) being differentially methylated (C2D5 vs. C1D1, n = 11, paired t-test; p < 0.01). Main pathways affected included endosomal transport, K+ transport, cathecolamine secretion, etc. PDL1 staining in archival tissue showed tumor staining > 0 in 16 of 35 and tumor/stroma interface staining > 0 in 20 of 35 specimens. Antigen-specific cytotoxic T cell activity was increased in CD8+ cells from ascites (C2D5 vs. C1D1). Conclusions: G+P has modest anti-tumor activity in patients with PROC, but some patients experienced prolonged disease stabilization. Biomarkers of response are being investigated. Clinical trial information: NCT02901899.
Histopathologic validation of the sentinel node technique in early-stage cervical cancer patients.
Authors: Mathevet Patrice , Guani Benedetta , Ciobanu Andrea , Mery Lamarche Eliane , Boutitie Florent , Balaya Vincent , Lecuru Fabrice 
Published: May 2020

6028 Background: Sentinel lymph node biopsy (SLN) could be an alternative to systematic lymphadenectomy in early cervical cancer. SLN is less morbid and had shown a high sensitivity for metastasis detection. However, sensitivity of the SLN technique could be over evaluated because SLN are examined with ultrastaging and non sentinel nodes are only examined with routine techniques. The aim of this study was to validate the negative predictive value (NPV) of the SLN technique, with ultrastaging of SLN and non sentinel nodes (NSLN). Methods: We used the SENTICOL 1 study data, published in 2011. All nodes, SLN and NSLN have been secondarily subjected to ultrastaging. The ultrastaging consisted in sectioning every 200 µm and immunohistochemistry. A central reviewing of the positive slides and 10% of the negative slides was undertaken. Results: One hundred thirty-nine patients were included. SLNs were detected in 136 (97.8%) of the 139 patients. SLNs were found bilaterally in 104 (76.5%) of the 136 patients. 2056 NSLNs were identified (median = 13 NSLNs per patient [range 1-54]). Of 136 patients with SLNs detection, 23 had positive SLNs, after serial sectioning and IHC. NSLNs were metastatic in 8 patients. However, in case of bilateral SLN detection, the FN rate was 1/99 (1%) with detection of ITC in one NSLN from 99 bilateral negative SLNs. The NPV was 99% (0,99 [IC 95% = 0,97-1,00]). Conclusions: The pelvic SLN technic is a safe and trustfully technic to determine the nodal status in patients with early-stage cervical cancer. In case of optimal mapping with bilateral detection, NPV is 99% (IC 95% = 0,97-1,00).
Prexasertib, a cell cycle checkpoint kinase 1 inhibitor, in BRCA mutant recurrent high-grade serous ovarian cancer (HGSOC): A proof-of-concept single arm phase II study.
Authors: Lampert Erika Joelle , An Daniel , McCoy Ann , Kohn Elise C. , Annunziata Christina M. , Trewhitt Kathryn , Zimmer Alexandra Dos Santos , Lipkowitz Stanley , Lee Jung-min 
Published: May 2020

6038 Background: Preclinical data suggest cell cycle checkpoint inhibition induces greater cell death in BRCA mutant HGSOC by causing replication stress and dysregulation of DNA damage responses. We hypothesized that prexasertib, a cell cycle checkpoint kinase 1 (CHK1) inhibitor, would be active in BRCA mutated HGSOC patients. Methods: We conducted a single center, two-stage phase II study of prexasertib (105mg/m2 IV every 2 weeks) in HGSOC patients with known germline or somatic BRCA mutations. The primary endpoint was RECIST response rate (RR). Progression-free survival (PFS) and safety (CTCAE v4) were secondary endpoints. Baseline research biopsies and blood samples were collected for exploratory biomarker endpoints. Results: Between February 2015 and July 2019, 22 heavily pretreated (median 5 prior systemic therapies [1-12]) women with BRCA mutant HGSOC (median age 58.7 [44-74.8]) received at least one dose of prexasertib. 13 (59%) patients were secondary platinum-resistant (median 8 [3-12] prior therapies) and 9 (41%) maintained platinum-sensitivity (median 4 [1-5] prior therapies). All but one received prior PARP inhibitor (PARPi) either in combination (10 [48%]) or as monotherapy (11 [52%]), with a median 5 month [mo; 1-29] PARPi-free interval prior to study entry. There was one complete response (41+mo, platinum-sensitive, no prior PARPi) and one partial response (9+mo, platinum-sensitive, 13.5mo PARPi-free interval) yielding an 11% RR (2/18 evaluable). No response was seen in platinum-resistant patients with prior PARPi. Median duration on study treatment was 4mo [1-9] among 21 patients with prior PARPi and 4mo [1.5-9] among 17 evaluable patients with prior PARPi. Common (>10%) grade 3/4 adverse events were neutropenia (82%), leukopenia (64%), and thrombocytopenia (14%); only one patient had grade 3 febrile neutropenia. 16 of 18 (89%) patients with grade 3/4 neutropenia received prophylactic growth factors for subsequent treatments. Conclusions: Prexasertib is tolerable and has modest activity in heavily pretreated BRCA mutant HGSOC patients. Further evaluation of predictive biomarkers for exceptional responders is ongoing. Clinical trial information: NCT02203513.
Quality of life, vascular endothelial growth factor inhibition, and survival outcomes with combination oral metronomic therapy in platinum refractory epithelial ovarian carcinoma: Results from a randomized study.
Authors: Sharma Aparna , Khurana Sachin , Malik Prabhat Singh , Singh Mayank , Mathur Sandeep , Kumar Sunesh , Sreenivas Vishnu kumar , Kumar Lalit 
Published: May 2020

6048 Background: Patients with recurrent and refractory epithelial ovarian cancer (EOC) have dismal outcomes. We evaluated a combination of oral metronomic therapy in platinum refractory EOC vis-à-vis angiogenic marker expression and its impact on patient reported outcomes. Methods: Between October 2017 and September 2019, 75 patients were randomized to receive etoposide (VP-16) (50 mg daily for 14 days) cyclophosphamide (50 mg daily for 28 days) (Arm A, n = 38) or etoposide (VP-16) (50 mg daily for 14 days) cyclophosphamide (50 mg daily for 28 days) and pazopanib (400 mg daily 28 days) every 28 days (Arm B, n = 37). Eligibility criteria included histopathological diagnosis of EOC, platinum refractory disease and ECOG performance status 0-2. Primary endpoint was serological progression free survival (PFS) as defined by Rustin criteria. Quality of Life (QoL) (evaluated using the EORTC QLQC30 and OV 28 questionnaires) and serum vascular endothelial growth factor (VEGF) were ascertained at baseline and after 3rd and 6th cycle. Intention to treat analysis was done. Results: Baseline characteristics were well matched in 2 arms. At a median follow up 14.4 months (95% CI 13.2-15.7), the median serological PFS is better for patients in Arm B 5.1 months (95%CI 3.13-10.33) compared to 3.4 months (95%CI 3-6.53) in arm A ( P= 0.045). Median overall survival (OS) is not reached in arm B versus 11.2 months (95%CI 5.66-NR) in arm A (P= 0.032). Disease progression was seen in 42.1% (n = 16) in Arm A versus 40.5 %(n = 15) in arm B ( P= 0.40). Sixteen patients are maintaining response. Mucositis (29.7% n = 11) and fatigue (13.5%, n = 5) were more in the pazopanib-containing arm ( P= 0.36). Serum VEGF demonstrated significant decline with subsequent cycles of therapy {median values (range): Arm A, baseline; 466.0 pg/mL(123.9-1930) vs. 6 cycles; 92.05pg/ mL(42.34-279.5) P< 0.0001; Arm B, baseline; 382.0 pg/mL(49.44-2054.0) vs 6 cycles; 119.7 pg/mL(18.20-367.5) P= 0.013} without any difference between the two arms ( P= 0.18). QoL symptom scales in both QLQC 30 and OV 28 questionnaires indicated small but significant improvement in pazopanib arm ( P= 0.02) without differences in global (p = 0.96) and physical functioning scales. ( P= 0.68). Conclusions: Addition of pazopanib to etoposide and cyclophosphamide resulted in improvement in serological PFS and OS with a well-tolerated toxicity profile and modest improvement in QoL.Serum VEGF expression requires validation in a larger cohort. Clinical trial information: CTRI/2017/10/010219.
Pharmacokinetics and safety following a single oral dose of niraparib in patients with moderate hepatic impairment.
Authors: Akce Mehmet , El-Khoueiry Anthony B. , Piha-Paul Sarina Anne , Bacque Emeline , Pan Peng , Zhang Zhi-Yi , Ewesuedo Reginald , Gupta Divya , Milton Ashley , Judson Patricia , O'Bryant Cindy L. 
Published: May 2020

6054 Background: Niraparib is approved for the maintenance treatment of adult patients (pts) with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy, or with similar cancers but advanced, associated with homologous recombination deficiency (HRD) and have been treated with ³3 prior chemotherapy regimens. Niraparib is extensively metabolized in the liver and eliminated via both hepatobiliary and renal routes. Objectives of this study included characterization of niraparib pharmacokinetics (PK) and safety in pts with normal hepatic function vs. pts with moderate hepatic impairment. Methods: This phase I, open-label, parallel-group, single-dose study enrolled pts with advanced solid tumors into 2 groups: normal hepatic function and moderately impaired hepatic function, defined as bilirubin >1.5 to 3 times the upper limit of normal and any aspartate aminotransferase elevation. Pts received a single 300-mg dose and underwent PK sampling for 7 days. Exposure parameters included maximum concentration (Cmax), area under the concentration-time curve calculated to last measured concentration (AUClast), and extrapolated to infinity (AUCinf). PK parameters were determined using a non-compartmental analysis in WinNonlin. Results: Seventeen pts were enrolled; 9 with normal hepatic function and 8 with hepatic impairment. Niraparib Cmax was 7% lower in pts with moderate hepatic impairment compared with pts with normal hepatic function (Table). Overall exposure was increased in pts with moderate hepatic impairment, with niraparib AUClast and AUCinf increased 45% and 60%, respectively. Safety data during the PK phase of the study is consistent with the known profile for niraparib. Conclusions: Pts with moderate hepatic impairment experienced increased niraparib exposure which did not noticeably alter the toxicity profile in this population. Clinical trial information: NCT03359850. [Table: see text]
Risk stratified multidisciplinary ambulatory management of malignant bowel obstruction (MAMBO) program for women with gynecological cancers: Preliminary results from a prospective single-center study.
Authors: Liu Shiru Lucy , Lee Yeh Chen , Jivraj Nazlin , Bowering Valerie , Wang Lisa , Bhat Gita , Madariaga Ainhoa , Kasherman Lawrence , Nathwani Kashish , Tesfu Azieb , Lee Sarah , Ferguson Sarah E. , Croke Jennifer M. , O'Brien Catherine , Lau Jenny , Chawla Tanya , Schlomovitz Eran , Oza Amit M. , Lheureux Stephanie 
Published: May 2020

6062 Background: Malignant Bowel Obstruction (MBO) is one of the most common and devastating complications in women with gynecological cancer (GC). There is currently no consensus guideline to improve patient (pt) care in this setting. MAMBO (NCT03260647) is an ongoing prospective study evaluating the clinical implementation of a novel management algorithm for multidisciplinary management of MBO in GC pts. We report preliminary patient outcomes. Methods: All GC pts at Princess Margaret Cancer Centre with a confirmed diagnosis of or are at risk of MBO are eligible for enrollment. Participants follow a low fiber diet titrated by severity of symptom and their monthly weight and albumin levels are recorded, along with standardized patient-reported outcome measures (PROMs) at different time points. For pts who develop MBO, inpatient and ambulatory management algorithms are applied using a multidisciplinary and interprofessional care model consisting of nurses, surgeons, oncologists, radiologists, nutritionists, total parenteral nutrition team, social work, and palliative care. Decisions regarding most optimal management strategies are made by this team with regular MAMBO rounds. A retrospective analysis of pts hospitalized with MBO between 2012 and 2017 was performed in order to have a historical comparison for outcome and survival analysis using Kaplan Meier methods. Results: Since August 2017, 70 pts have been enrolled in MAMBO. Most had high-grade serous ovarian carcinoma (75%), of whom 68% are platinum-resistant. So far, 36 (51%) developed MBO, 6 of whom had multiple sequential episodes. Mean number of days in hospital with MBO was 10 days (median 7, range 0-45), compared to 18 days (median 9, range 0-134) for historical control (p = 0.009). There was no significant loss in weight 6 months from MBO diagnosis but a significant reduction in albumin level by 2.75 g/L after 3 months (p = 0.005). PROMs suggest fatigue and general lack of wellbeing were the symptoms with highest distress. Most patients (78%) received chemotherapy following MBO and most received weekly paclitaxel (36%). Median time from first MBO to death was 219 days (95% CI: 101-not reached) for all-comers in MAMBO and 174 days (95% CI: 98-363) for MBO requiring hospitalization, compared to 108 days (95% CI: 79-160) for historical controls (p = 0.007 and p = 0.062, respectively). Conclusions: Patient care and outcomes from MBO seem to be improved in GC pts enrolled in MAMBO compared to historical controls. Clinical trial information: NCT03260647.
Juvenile granulosa cell tumor: An interim report from the international ovarian and testicular stromal tumor (OTST) registry.
Authors: Harris Anne , Nelson Alexander , Watson David , Mallinger Paige , Langford Miranda , Stering Allen , Turk Farheen , Billmire Deborah F. , Schneider Dominik T. , Frazier A. Lindsay , Dehner Louis P , Hill Ashley , Messinger Yoav H. , Schultz Kris Ann P 
Published: May 2020

6064 Background: Juvenile granulosa cell tumors (JGCT) are rare sex cord-stromal tumors which occur primarily in children and adolescents. Methods: All individuals or proxy caregivers provided informed consent/assent for participation in the International OTST Registry. Clinical data was collected. When available, pathology was centrally reviewed. Staging was evaluated using the International Federation of Gynecology and Obstetrics (FIGO) classification. Kaplan-Meier survival analyses and exact permutation tests were performed. Results: Forty-two individuals with ovarian JGCT were enrolled. Median age at diagnosis was 9 years (range 0-27). Most individuals had Stage I disease (Stage Ia=16; Stage Ib=1; Stage Ic=16). Seven individuals presented with higher stage (Stage II=2; Stage III=5). Stage was unknown for 2 individuals. Three-year overall survival (OS) was 88% (CI 77%, 100%) and event-free survival (EFS) was 69% (CI 54%, 88%). At median follow-up time of 25 months (range 0-416), 9 patients (Stage Ia=1, Stage Ic=5, Stage III=3) had recurrent disease. Use of post-operative adjuvant chemotherapy varied by stage and timing of rupture. Of those with Stage Ic JGCT, 2/7 with preoperative rupture and 3/9 with intraoperative rupture recurred. Among individuals with recurrence, median time to recurrence was 11.5 months (range 3-19). Four of 9 individuals with recurrence survived (no evidence of disease n=2; alive with disease n=2). All individuals who died presented with extrapelvic recurrence. Median time from recurrence to death was 10 months (range 2-53). In individuals with recurrence, advanced stage at diagnosis (HR 5.1; p-value 0.087) and recurrence outside the tumor bed (HR Infinity; p-value 0.048) were associated with inferior OS. Three-year OS for individuals with recurrence was 57% (CI 30%, 100%). Conclusions: Low stage JGCT is associated with a favorable prognosis, however, recurrence is associated with lower survival rate. Within this series, recurrences presented within 2 years of diagnosis. Novel strategies are needed to address recurrent and extrapelvic disease.
Financial toxicity and patient-reported outcomes over time: A longitudinal study of women with recurrent ovarian cancer.
Authors: Meyer Larissa , Schneider Amy , Chen Tsun Hsuan , Wang Xin Shelley , Sun Charlotte C. 
Published: May 2020

6079 Background: The chronic nature of treatment for ovarian cancer (OC) can place women at increased risk of financial toxicity (FT) from ongoing direct and indirect costs coupled with potential loss of income. We explored FT and its association with anxiety, depression, and quality of life over time in women with recurrent OC. Methods: Women with recurrent OC enrolled in a longitudinal study were given the following validated instruments at baseline and every 3 months: FACIT Comprehensive Score for Financial Toxicity (COST), GAD-7 (anxiety), CES-D (depression) and FACT-Ovary. Mixed models were performed on longitudinal data over 12 months of follow-up. Multivariable analysis of demographic data was performed. Results: 225 patients were divided into low FT (top 2 terciles, n = 152) and high FT (bottom tercile, n = 73,) by baseline COST scores. The median age was 59 (range 22.9-78.9). There were no significant differences between the groups in regards to marital status, number of people in household or education level. There were significant differences between the low and high financial toxicity groups in terms of median age (low FT = 61 yrs vs. high FT = 54 yrs, p < 0.0001); race (5.4% black in low FT vs. 15.1% in high FT, p = 0.04), number of children < 18 years in the home ((p = 0.02), employment status p( < 0.0001) and annual income p( < 0.0001). On multivariable analysis, only income and age remained significantly associated with FT. The mean baseline COST score in the low FT group was 34 vs. 16 in the high FT group. Interestingly, pts with low baseline FT had significant worsening of FT over the 12 month time period while those with high FT had slight improvement over time. Consistently, the high FT group had higher scores on screening measures for anxiety and depression, as well as lower overall quality of life which persisted over time. Conclusions: Financial toxicity is a measurable and clinically relevant patient reported outcome. The cohort of women with high FT demonstrated higher mean scores on screening measures for depression and anxiety as well as persistently lower quality of life. Targeted interventions to decrease financial toxicity may provide more global improvements in mental health and quality of life.