bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of endocrine therapy adherence on racial disparities in breast cancer survival.
Authors: Lee Kimberley T , Buhlmann Melanie , Gwede Clement K , Gore L. Robert , Pan I-Wen , Luo Yi , Tworoger Shelley S , Vadaparampil Susan Thomas , Jim Heather S.L. 
Published: June 2023

541 Background: Black women have worse breast cancer outcomes compared to their White counterparts, even for hormone receptor positive (HR+) HER2 negative (HER2-) breast cancer (BC). This tumor type is usually treated with 5-10 years of adjuvant endocrine therapy (ET) to reduce risk of BC recurrence and improve survival. We investigated the impact of adherence to ET on racial differences in survival for HR+ HER2- BC survivors. Methods: We conducted a population-based, retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, which links demographic and clinical data with cause of death for persons with cancer and Medicare claims for covered health services. We examined 9,039 women with HR+ HER2- stage I-III BC diagnosed between 2007 and 2016, who received primary breast surgery and initiated ET. Adherence to ET was measured using the medication possession ratio (MPR), which assesses the proportion of time a patient has medication available via filled prescriptions. As in established literature, we defined ET adherence as MPR > = 80%. Causal mediation analysis was performed to measure to impact of adherence on survival disparities between Black and White BC survivors. Results: Mean age at diagnosis was 72 years, 6.5% were Black, and 20.9% were dual eligible for Medicaid (a surrogate for socioeconomic hardship). Most had stage I or II breast cancer (69.3%) and mastectomy as primary surgery (69.7%). Nineteen percent received chemotherapy and 62.5% received radiation. In univariate analyses, factors associated with ET adherence were Black race (OR 0.62, 95% CI 0.54-0.75), insured by Medicaid (OR 0.72, 95% CI 0.65-0.81), being married (OR 1.14, 95% CI 1.03-1.25), and increased comorbidities (Charlson score > = 2) (OR 0.88, 95% CI 0.78-0.99). Age, BC stage, type of surgery, and receipt of chemotherapy or radiation were not associated with ET adherence. In multivariable models adjusting for age, race, marital status, Medicaid eligibility, and Charlson score, Black race and Medicaid eligibility remained inversely associated with ET adherence (OR 0.70, 95% CI 0.59-0.83 and OR 0.77, 95% CI 0.69-0.87 respectively). Among those who were adherent to ET, Black women had 43% higher risk of mortality compared to White women (HR 1.43, 95% CI 1.17-1.76). In mediation analysis, 4.25% of the observed survival disparity between Black and White women can be explained by differences in ET adherence. Conclusions: We identified racial disparities in ET adherence and overall survival among women with BC. Adherence to ET accounted for a small percentage of racial disparities in survival. Further research is needed to delineate other factors contributing to ET non-adherence among Black women and to investigate additional factors contributing to known disparities in BC survival.
Validation of a novel and rapid reagent free assay to predict outcomes for adjuvant therapy decision making in hormone receptor-positive breast cancer.
Authors: Coombes Charles , Amrania Hemmel , Angelou Christina , Al-Khalili Zamzam , Ellis Ian O. , Francescatti Darius , Phillips Chris , Green Andrew R. , Wright Nicholas , Rakha Emad A. , Palmieri Carlo 
Published: June 2023

545 Background: Digistain is a mid-infrared imaging technology that assesses aneuploidy by measuring the nuclear-to-cytoplasmic chemical ratio in the cellular content of tissues to generate the Digistain Index (DI). DI correlates with tumor grade and shows promise for risk stratification. Here we investigated whether DI could predict clinical outcomes in patients with early breast cancer to guide decision making regarding subsequent adjuvant chemotherapy. Methods: Infrared spectrometry was performed on existing tissue microarrays to determine the DI of 801 patients with hormone receptor-positive, HER 2-negative primary breast cancer with ≤3 positive lymph nodes who had received systemic endocrine therapy only. Multivariate logistic modelling incorporated the DI with pathological features to generate the Digistain Prognostic Score (DPS). Receiver operator characteristics curves were used to assess the ability of DPS to predict 5- and 10-year progression-free survival (PFS), recurrence and overall survival (OS). Results: In a Cox-regression analysis, the hazard ratio (HR) of DI to predict OS was 4.49 (95% CI 1.08–18.67; P=0.039) compared with HRs in the range of 1.04–1.81 (all P < 0.001) for age, tumor grade, tumor size and lymph node stage. In multivariate modelling analysis, DPS was consistently highly accurate and had negative predictive values for PFS, recurrence, and OS at 5 and 10 years that were similar, if not superior, to existing genomic-based tests. Using the DPS, the HRs for Kaplan-Meier curves for low- vs. high-risk classification were statistically significant (P<0.001) for PFS, recurrence and OS (1.80, 1.83 and 2.49, respectively). Conclusions: In patients with early breast cancer, DPS showed high accuracy and predictive performance, and was able to stratify patients into low or high risk. Considering its low cost and ability to provide almost immediate prognostic information, DPS has the potential to offer clinical utility to reduce the use of unnecessary chemotherapy.
Cardiac safety and efficacy for patients with early-stage breast cancer treated with pegylated liposomal doxorubicin (PLD) or doxorubicin.
Authors: Tang Lichen , He Min , Wu Jiong , Wang Zhonghua , Liu Guangyu , Yu Keda , Geng Cuizhi , Fan Zhimin , Ling Rui , Qiao Guangdong , Cai Li , Luo Ting , Jin Feng , Wang Haibo , Zhang Anqin , Zhang Hongwei , Zeng Xiaohua , Wang Xiaojia , Jiang Ming , Zhimin Shao 
Published: June 2023

550 Background: Anthracyclines play an important role in the treatment of breast cancer (BC) while cardiotoxicity, a serious side effect, limits the clinical application. Pegylated liposomal doxorubicin (PLD) is a new dosage form of doxorubicin encapsulated in liposomes, which can reduce the plasma free level of doxorubicin and drug to normal tissue delivery, thereby reducing cardiotoxicity. The aim of this study was to evaluate the cardiac safety and efficacy of PLD compared with doxorubicin as adjuvant therapy in breast cancer patients. Methods: This is an open-label, randomized trial involving patients with operable breast cancer who were at high risk of recurrence after radical sugery (NCT03949634). Patients were randomized (1:1) to receive adjuvant PLD or doxorubicin (A) and cyclophosphamide followed by taxanes ± trastuzumab. The primary endpoint was cardiotoxicity, which was defined as congestive heart failure (CHF) with clinical symptoms, or no symptoms but with an abnormal left ventricular ejection fraction (LVEF). Secondary endpoints included 5-year disease-free survival (DFS) rate, 5-year overall survival (OS) rate and safety. Results: Between November 2017 and September 2019, 247 patients were randomized and received study treatment (PLD arm, 131; A arm, 116). The median age was 49 years (range, 26-67) in PLD arm and 48 years (range, 25-70) in A arm. The pathological stages were 18.3% stage I, 58.0% stage II, and 22.1% stage III in PLD arm, while those of A arm were 20.7% stage I, 59.5% stage II, and 19.8% stage III. The median follow-up time was 43.0 months. The incidence of abnormal LVEF was 0 in the PLD arm and 1.7% the A arm (P = 0.220). The incidence of CHF was 0 in the PLD arm and 0.9% the A arm (P = 0.470). Survival data analysis is immature. The exploratory analysis of cardiac-related biomarkers showed that the incidence of high-sensitivity cardiac troponin-T (hs-cTnT) was lower in PLD arm than in A arm (3.8% vs. 30.2%, P < 0.001). Grade 3/4 adverse events (AEs) occurred in 42.7% patients in PLD arm and in 61.2% patients in A arm. The most common grade 3/4 AEs in PLD arm and A arm included neutropenia (34.4% vs. 55.2%), leukopenia (30.5% vs. 39.7%), and hand-foot syndrome (4.6% vs. 0.0%). Conclusions: Hs-cTnT elevation may have a role in the AE prediction of antharcycline. PLD usage may present lower incidence of cardiotoxicity than doxorubicin in the adjuvant treatment of patients with early-stage breast cancer. Clinical trial information: NCT03949634 .
In situ immune impact of nivolumab + ipilimumab combination before standard chemoradiation therapy (RTCT) for FIGO IB3-IVA in patients (pts) with cervical squamous carcinoma: COLIBRI trial, a GINECO study.
Authors: Ray-Coquard Isabelle Laure , Kaminsky-Forrett Marie-Christine , Ohkuma Ryotaro , De Montfort Aymeric , Joly Florence , Treilleux Isabelle , Ghamry-Barrin Sarah , Bello-Roufai Diana , Saintigny Pierre , Angelergues Antoine , Michon Lucas , Hardy-Bessard Anne-Claire , Lainé Alexandra , Savoye Aude-Marie , Berthet Justine , Caux Christophe , Lecuru Fabrice , Dubois Bertrand , Lagarde Bétrian Sarah 
Published: June 2023

5501 Background: We report the results of a window-of-opportunity phase 2 trial using neoadjuvant nivolumab + ipilimumab followed by standard chemoradiation therapy (RTCT) in cervical squamous cell carcinoma pts using the CD8+/FOXP3+ ratio as a surrogate marker of immune checkpoint blockade (ICB) in situ effect. Association with better clinical outcome after neoadjuvant chemotherapy and higher CD8+/FOXP3+ ratio was described in cervical cancer pts. However, immune modulation after ICB and correlation with treatment response needs to be characterized. Methods: The primary objective was to explore the changes in the ratio of CD8+/FOXP3+ in tumor biopsies performed before and after ICB (prior to standard RTCT) by multiplex-immunofluorescence (mIF) analyzing densities of CD8 effector T cells (CD8+: CD3+CD8+FOXP3-) and CD4 regulatory T cells (FOXP3+: CD3+CD8-FOXP3+). To normalize the distribution of the values, mIF data were log-transformed (log10). Targeted gene expression profiling of 2,549 genes using HTG technology allowed us to evaluate the 27-gene based ‘HOT’ score reported to be associated with immunologically active tumors (Foy J-P. et al., 2022, Eur J Can). Results: Pts received 1 cycle of nivolumab 3 mg/kg (D1D15) + ipilimumab 1 mg/kg (D1) before starting RTCT + brachytherapy. After RTCT, pts could continue nivolumab in maintenance 480 mg total dose every 28 days for 6 months. Forty pts were treated (including 50% FIGO III-IV). There were no new or unexpected toxicity. Grade≥3 AEs related to ICB occurred in 3 pts. mIF data of the 28 evaluable pts revealed an increase of total CD8+ cells (Wilcoxon, p=0.009), proliferating CD8+ cells (p=0.002) and CD8+/FOXP3+ ratio (p=0.03) between baseline and before RTCT. In the 37 pts evaluable by HTG, a significant increase of expression of the CD8A gene (paired t-test, p=2.2e-05) and the ‘HOT’ score (paired t-test, p=3.1e-06) was observed after ICB. The Objective Response Rate on primary tumor before, after, at the end of treatment (EOT) is reported in table. Correlation between CD8+/FOXP3+ ratio, the ‘HOT’ score and response to treatment will be presented. Conclusions: These data indicate that neoadjuvant nivolumab + ipilimumab is safe and orchestrates de novo immune responses in cervical squamous cell carcinoma. The 82.5% CR rate on primary tumor 6 months post RTCT suggests favorable clinical outcomes. Clinical trial information: NCT04256213 . [Table: see text]
Influence of adherence to adjuvant endocrine therapy in early breast cancer: Results from a large German real-world claims data analysis.
Authors: Dannehl Dominik , Engler Tobias , Dijkstra Tjeerd , Gutsfeld Raphael , von Au Alexandra , Hahn Markus , Hawighorst-Knapstein Sabine , Chaudhuri Ariane , Wallwiener Markus , Bauer Armin , Brucker Sara , Wallwiener Stephanie , Hartkopf Andreas Daniel 
Published: June 2023

551 Background: In hormone-receptor positive (HR+) early breast cancer (EBC) adjuvant endocrine therapy (ET) significantly reduces recurrence and mortality. The most common way to estimate therapy adherence is the use of patient reported outcome measures. Yet, this method is inaccurate due to the social-desirability bias. We therefore aimed to analyze adherence to ET over the first 5 years of treatment by using claims data from a large German health insurance provider (AOK Baden-Wuerttemberg). Methods: Female patients diagnosed with HR+ EBC between July 1st 2010 and December 31st 2019 were included into the analysis. Adherence to ET was defined as the ratio of the summed number of pills of filled prescriptions for ET (either aromatase inhibitors or tamoxifen) and the duration of endocrine therapy in days (from the start of the first prescription after completion of surgery and chemotherapy, if applicable). ET administration was observed over 5 years. High/low adherence was defined as a ratio between 0.8 – 1 and 0 – 0.8, respectively. ET duration was divided into yearly intervals and adherence was calculated as above. Continuous high/low adherence was then defined as an adherence between 0.8 – 1 and 0 – 0.8 in each year. Distant recurrence-free survival (DRFS) was calculated from the day of the first diagnosis of EBC until onset of distant metastatic disease. Overall survival (OS) was defined as the period between first diagnosis of EBC until death. Results: In total, 20998 patients were included. 17006 patients (81%) were HR+. Regarding overall adherence during the first 5 years, average adherence was 0.81 ± 0.26, with 72% of all HR+ patients showing high adherence to ET. Of 17006 HR+ EBC patients, 8363 (49%) showed a continuous high adherence to ET and 1731 (10%) showed a continuous low adherence to ET over 5 consecutive years. Continuous adherence to endocrine therapy had a significant impact on DRFS (HR: 0.61; 95% CI: 0.52 - 0.71; p < 0.0001) and OS (HR: 0.52; 95% CI: 0.46 -0.59; p < 0.0001). The 10-year OS rate was 79% / 64% for patients with continuous high / low adherence to endocrine therapy. Conclusions: As measured by the number of prescribed pills, adherence during the first 5 years of endocrine therapy was higher than expected by literature. Continuous adherence to ET over 5 years has a significant impact on OS and DRFS. Future research should focus on identifying factors that influence therapy adherence in HR+ EBC patients.
Correlation of cyclin E1 expression and clinical outcomes in a phase 1b dose-escalation study of azenosertib (ZN-c3), a WEE1 inhibitor, in combination with chemotherapy (CT) in patients (pts) with platinum-resistant or refractory (R/R) epithelial ovarian, peritoneal, or fallopian tube cancer (EOC).
Authors: Liu Joyce F. , Fu Siqing , Richardson Gary Edward , Vranjes Zivko , Meniawy Tarek , Shannon Catherine M. , Hamilton Erika P. , Blank Stephanie V. , Mathews Cara Amanda , Alidzanovic Jasmina , Ruseva Rossitza Krasteva , Shi Qing , Harismendy Olivier , Ptaszynski Ann M. , Westin Shannon Neville , Meric-Bernstam Funda , Thaker Premal H. 
Published: June 2023

5513 Background: Azenosertib (ZN-c3) is a novel, selective, and orally bioavailable WEE1 inhibitor demonstrating single-agent antitumor activity. Azenosertib may inhibit CT-induced DNA damage repair and provide benefit in pts with platinum R/R EOC. Cyclin E1 amplification/overexpression is present in ≥35% of metastatic ovarian cancer. High expression/amplification of Cyclin E1 is a poor prognostic marker and predictive of lack of response to platinum-based CT. Ovarian models overexpressing Cyclin E1 have exquisite sensitivity to azenosertib in vitro and in vivo; forced Cyclin E1 overexpression sensitizes cell lines with low endogenous Cyclin E1 to azenosertib. Methods: This open-label, multicenter study (NCT04516447) assessed azenosertib + paclitaxel (PAC), carboplatin (Carbo), gemcitabine (GEM), or pegylated liposomal doxorubicin (PLD) in pts with metastatic high-grade serous EOC after ≤2 lines of CT including platinum CT. Primary endpoint is safety and identification of RP2D of each combination. Secondary endpoints include clinical activity. Azenosertib was given continuously or intermittently QD in 21 or 28D cycles until PD or unacceptable toxicity. Results: 103 pts were enrolled; at data cut-off, 94 were efficacy evaluable. 26.6% had a partial response (PR) and median progression free survival (PFS) = 9.03 mo (95%CI: 5.52-11.01). Azenosertib + PAC demonstrated the highest ORR [9/18 (50%)], followed by Carbo [9/27 (33.3%)]; ORR for azenosertib + PLD or + GEM was 14.3% (5/35, 2/14 respectively). 80 pts had available Cyclin E1 expression data by IHC; higher Cyclin E1 (H-score >50) correlated with higher ORR and longer PFS (ORR = 31.3% vs 7.7%; PFS = 10.35 vs 3.25 mo, HR=0.3; Table). Frequent Grade ≥3 TEAEs (%) were neutropenia (44.4), thrombocytopenia (30.3), anemia (12.1), leukopenia (11.1), fatigue (10.1), diarrhea (6.1), nausea (5.1), and vomiting (5.1). Conclusions: Azenosertib + CT is well tolerated and has encouraging clinical activity, with durable responses in pts with platinum R/R EOC. Pts with Cyclin E1 overexpressing tumors, a subgroup with suboptimal benefits from CT, demonstrated significant improvements in ORR and PFS vs pts with tumors having low expression. These data support a planned trial of azenosertib + CT vs CT alone in Cyclin E1 overexpressing platinum R/R EOC. Clinical trial information: NCT04516447 . [Table: see text]
A phase II trial of palbociclib combined to letrozole after progression on second-line chemotherapy for women with ER/PR-positive high-grade serous or endometrioid ovarian, fallopian tube, or peritoneal cancer: LACOG 1018.
Authors: Damian Fernanda Bronzon , Melo Andreia Cristina De , Zibetti Dal Molin Graziela , Rodrigues Angelica Nogueira , Calabrich Aknar Freire de Carvalho , Werutsky Gustavo , Filho Elias Abdo , Rebelatto Taiane Francieli , de Jesus Rafaela Gomes , Jimenez Mirela Foresti 
Published: June 2023

5514 Background: Treatment options for patients with high-grade ovarian serous (HGSC) or endometrioid carcinoma (HGEC) who progress after receiving chemotherapy for recurrence are limited. Methods: LACOG 1018, a phase II, single-arm, multicenter trial evaluated the efficacy of letrozole 2.5mg/day po continuously plus palbociclib 125mg/day po for 21 days in 28-day cycles in patients with histologically proven ovarian HGSC or HGEC, fallopian tube or peritoneal cancer who had progressed on prior chemotherapy for locoregional recurrence or metastatic disease (at least one platinum-based regimen). Patients had centrally confirmed ER and/or PR positivity (> 10% by immunohistochemistry) and ECOG PS 0-2. The primary endpoint was progression-free survival (PFS) at 12 weeks by RECIST 1.1. Secondary endpoints were overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR) and safety. Tumor evaluations were performed every 6 weeks until week 24. Sample size was calculated as 31 patients for the primary endpoint (90% power to detect a two-sided significance level of 5%, 45% PFS at 12 weeks) and 39 patients for secondary endpoints considering 10% drop-out. NCT03936270. Results: A total of 41 eligible patients were included in five Brazilian centers between Feb2020-Jan2022 (table). The PFS-week12 rate was 63.4% (95%CI 46.8 – 76.1). At the time of analysis (cut-off date Jan 18th, 2023) median follow-up was 18.1 months (95%CI 12.9 – 24.3), and 37 PFS events had occurred. Median PFS was 4.2 months (95%CI 2.7 – 5.5) and median OS was 13.4 months (95%CI 10.4 – 20.1). The ORR was 7.7% (N=3 PR) and the CBR was 71.8%. Treatment-related adverse event rates of any grade and grade 3-4 were 95.1 % and 51.2 %, respectively. Grade 3-4 neutropenia was reported in 17 (41.5%) patients, and febrile neutropenia in 1 (2.4%). Only one patient (2.4 %) discontinued the treatment due to toxicity. At the cut-off date, three patients remained on treatment. Conclusions: Palbociclib combined to letrozole demonstrated a significant efficacy in terms of PFS rate at 12 weeks (63.4%) and CBR (71.8%), with no new safety concerns in women with recurrent advanced and metastatic hormone receptor-positive ovarian cancer. These results warrant further investigation of palbociclib plus letrozole in high-grade ovarian cancer. Clinical trial information: NCT03936270 . [Table: see text]
Camrelizumab plus apatinib in patients with advanced or recurrent endometrial cancer after failure of at least one prior systemic therapy: A single-arm phase II trial.
Authors: Wang Huaying , Tian Wenjuan , Ren Yulan , Lu Jing , Wang Tingting , Li Haiming , Jing Chuyu , Shan Boer , Yang Huijuan , Cheng Xi 
Published: June 2023

5516 Background: The first stage results of a Simon’s two-stage single-arm phase II trial showed promising antitumor activity and manageable safety of camrelizumab (a humanized anti-PD-1 monoclonal antibody) plus apatinib (a highly selective VEGFR2 inhibitor) in patients with advanced or recurrent endometrial cancer after failure of prior systemic therapy. Here, we report the primary results of this trial. Methods: This open-label, single-arm, phase II trial used a minimax Simon’s two-stage design. Patients with advanced or recurrent endometrial cancer that had progressed after at least one prior systemic therapy were treated with camrelizumab (200 mg, intravenously, every two weeks) and apatinib (250 mg, orally, daily) on a four-week cycle until disease progression or intolerable toxicity. The primary endpoint was the objective response rate per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Other assessed endpoints were disease control rate, time to response, duration of response, time to treatment failure, progression-free survival, overall survival, and treatment-related adverse events. Results: Between January 20, 2020 and October 14, 2022, 36 patients (median age: 60 [range: 29, 76] years; 17 [47.2%] had Eastern Cooperative Oncology Group [ECOG] performance status 1; 15 [41.7%] had received at least two prior systemic therapies) were enrolled. At the date of data cutoff (December 31, 2022), the median follow-up time was 13.9 (interquartile range: 5.8-23.2) months. All 36 patients were evaluable for efficacy, the confirmed objective response rate was 44.4% (95% CI: 27.9%, 61.9%) and the conformed disease control rate was 88.9% (95% CI: 73.9%, 96.9%), with two complete response, 14 partial response, and 16 stable disease. The median progression-free survival was 6.4 (95% CI: 5.2, 13.0) months. The treatment-related adverse events of grade 3 or greater occurred in 19 (52.8%) patients, with increased gamma-glutamyltransferase (8 [22.2%]), hyperglycemia (4 [11.1%]), hypertension (4 [11.1%]) and increased direct bilirubin (4 [11.1%]) being most common. Reactive cutaneous capillary endothelial proliferation occurred in 6 (16.7%) patients and all were grade 1 or 2. No treatment-related death occurred. Conclusions: Camrelizumab plus apatinib show promising antitumor activity and manageable toxicity in patients with advanced or recurrent endometrial cancer after failure of prior systemic therapy and warrant further investigation. Clinical trial information: ChiCTR2000031932 .