bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of fulvestrant and abemaciclib in hormone receptor positive advanced or recurrent endometrial cancer.
Authors: Green Angela , Zhou Qin , Iasonos Alexia , Zammarrelli William , Weigelt Britta , Ellenson Lora H , Chhetri-Long Rashmi , Shah Pooja , Hom Vania , Erinjeri Joseph P. , Petkovska Iva , Chandarlapaty Sarat , Cohen Seth M. , Grisham Rachel N. , Konner Jason A. , Rubinstein Maria M , Tew William P. , Troso-Sandoval Tiffany A. , Aghajanian Carol , Makker Vicky 
Published: June 2024

5511 Background: Inhibition of the Cyclin D-Cyclin dependent kinase (CDK)4/6-INK4-retinoblastoma pathway can overcome acquired or de novo treatment resistance to endocrine monotherapy. Elevated CDK4 expression is observed in 34–77% of endometrioid endometrial cancers (ECs) and is an early event of neoplastic transformation. Responses to endocrine monotherapy in advanced or recurrent EC are suboptimal and short-lived. We hypothesized that CDK4/6 inhibition with abemaciclib combined with fulvestrant is a promising strategy to improve outcomes with endocrine therapy in patients (pts) with advanced or recurrent hormone receptor-positive EC. Methods: This was an investigator-initiated, open label, single arm phase II study in pts with advanced or recurrent EC. Eligibility criteria included age ≥18 years, estrogen receptor or progesterone receptor expression ≥ 1% by immunohistochemistry, measurable disease, ≤ 2 prior lines of chemotherapy, and ≤ 1 prior line of hormonal therapy. All histologies were eligible except carcinosarcoma. Mixed histologies required ≥ 95% endometrioid component. Pts received fulvestrant 500 mg intramuscularly monthly with an initial 2-week loading dose and abemaciclib 150 mg orally twice daily until disease progression or prohibitive toxicity. Primary endpoint was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors v1.1. Results: At data cutoff (October 7, 2023), 27 pts initiated protocol therapy and 25 pts were evaluable for efficacy. 24 pts (89%) had tumors with endometrioid histology. 9 pts (33%) had prior hormonal therapy and 26 pts (96%) had ≥1 prior line of chemotherapy. 11 pts achieved a partial response resulting in an ORR of 44% (90% CI, 27.0% to 62.1%). The median duration of response, among pts that experienced a response, was 15.6 months (90% CI, 7.2 – nonestimable (NE)). All responses were in grade 1 or 2 endometrioid ECs. 10 out of 11 responses (91%) were in pts with copy number low/no specific molecular profile ECs, while 1 response (9%) was in a patient with microsatellite instability-high EC. Median PFS was 9.0 months (90% CI 1.8 to 20.4) and median OS was 37.8 months (90% CI 16.3 to NE). Most common ≥ grade 3 treatment related adverse events were neutropenia (22%) and anemia (19%). Conclusions: The combination of abemaciclib and fulvestrant has promising activity with durable responses observed in pts with advanced or recurrent EC; a phase 3 trial is planned. Clinical trial information: NCT03643510 .
A single-arm, phase II trial assessing the combination of AK105 and anlotinib in first-line treatment for persistent, recurrent, or metastatic cervical cancer.
Authors: Guo Ruixia , Qiu Haifeng , Wang Qian , Su Ke , Chang Lei , Cai Mingbo , Mao Meng , Bian Aiping 
Published: June 2024

5530 Background: Anlotinib, a small molecule antiangiogenic drug, which can inhibit multiple tyrosine kinase receptor activity, had been proven effective and well-tolerant in patients with recurrent or metastatic cervical cancer who had received two or more lines of prior treatments. AK105 is a novel human immunoglobulin G1 (IgG1) anti-programmed cell death-1 (PD-1) antibody. This single-arm, phase Ⅱ clinical trial aimed to assess the efficacy and safety of AK105 plus anlotinib as fist-line therapy for persistent, recurrent, or metastatic cervical cancer. Methods: Patients with pathologically diagnosed persistent, recurrent, or metastatic cervical cancer were eligible for this study. They should have previously received platinum-based systemic chemotherapy and currently not suitable for local treatment like radiotherapy or surgery, with ECOG PS 0-1. Prior use of immune checkpoint inhibitors or antiangiogenic agents was excluded. The designed doses were: AK105, 200mg, IV, Q3W; anlotinib, 12mg, PO, QD, 2 weeks on/1 week off, Q3W. The treatment will last as long as two years, while should be halted by disease progression, or unacceptable toxicities. The primary endpoint was the objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression free survival (PFS), duration of response (DoR), overall survival (OS) and safety. Results: From Apr 2022 to Dec 2023, 15 patients were recruited with a median age of 50 years (range: 31-74). 9 patients were PD-L1 expression positive (CPS≥1), 1 negative and 5 NA. 73.3% patients were confirmed as squamous cell carcinoma. At the data cutoff date (Dec 29, 2023), 10 patients had received at least once tumor efficacy evaluation. 6 (6/10, 60.0%) patients achieved PR, 2 (2/10, 20.0%) patients achieved SD, and 2(2/10, 20.0%) patient PD. The ORR was 60.0% (95% IC, 26.2%-87.8%) and DCR was 80.0% (95% IC, 44.4%-97.5%). Incidence of any grades TRAEs was 86.7%. Grade 3 TRAEs incidence was 33.3% including hypertension (1/15, 6.7%), thrombocytopenia (1/15, 6.7%), elevated alanine aminotransferase (1/15, 6.7%), adrenal insufficiency (1/15, 6.7%), and rash (1/15, 6.7%), pulmonary infection (1/15, 6.7%). No Grade 4 or death occurred. Conclusions: This chemo-free therapy of AK105 plus anlotinib in the first-line treatment with persistent, recurrent, or metastatic cervical cancer showed promising efficacy with favorable toxicity profile. More data will be reported in the future. Clinical trial information: NCT05137171 .
Prognostic analysis of nimotuzumab combined with concurrent chemoradiotherapy in locally advanced cervical cancer: A multicenter real-world study.
Authors: Li Jiwei , Wu Tao , Cai Manbo , Xie Changjun , Ding Sijuan , Zou Wen , Wang Jingjing 
Published: June 2024

5532 Background: Nimotuzumab is a monoclonal antibody against EGFR, which can improve the radiotherapy efficacy of nasopharyngeal carcinoma with EGFR positive. Most cervical cancers are induced by virus and express EGFR. Therefore, this study explores the efficacy and safety of Nimotuzumab combined with concurrent chemoradiotherapy (CCRT) in locally advanced cervical cancer (LACC). Methods: Information on patients with stage IIB-IVa cervical cancer who received CCRT combined with Nimotuzumab or CCRT alone at five cancer centers from January 2021 to December 2022 were collected. Nimotuzumab was administered 200mg once a week for a total of 6 weeks, starting on the same day as CCRT. The imaging examination was carried out 2 months after the end of radiotherapy. The reduction rate of lesions = (pre-treatment diameter - post-treatment diameter)/pre-treatment diameter. Patients were classified into the Nimotuzumab group and No-Nimotuzumab group. Categorical variables were compared using the χ2 test or Fisher’s exact test. Clinical outcomes were analyzed using the Kaplan–Meier method with log-rank test. Results: There are 224 patients enrolled, median age 57 years (32–90 years). The median follow-up time was 20 months (12–36months). The 2-year overall survival (OS) and progression-free survival (PFS) rates were 93% and 89.5%, respectively. The objective response rate (ORR) was 91.96%. There were 64 patients in Nimotuzumab group and 160 patients in No-Nimotuzumab group. The number of patients in Nimotuzumab group with stage IIIC and IVa, as well as those without chemotherapy, is higher than that in No-Nimotuzumab group. There was no significant difference between the Nimotuzumab and No-Nimotuzumab groups in terms of 2-year OS rate (93.2% vs.93%, p = 0.895), and PFS rate (96.2% vs.90.4%, p = 0.645). However, The Nimotuzumab group has a better CR rate (53.13% vs. 35%, P=0.012), ORR (98.44% vs. 89.38%, p=0.024), and reduction rate of cervical lesions (79.26% vs.70.94%, p=0.046) compared to the No-Nimotuzumab group (Table). Also, there was no significant difference between the Nimotuzumab and No-Nimotuzumab groups in terms of hematological toxicity (89.83% vs. 94.48%, p=0.730), nausea and vomiting (35.59% vs. 38.19, p=0.865), radiation proctitis (45% vs. 33.1%, p=0.371), radiation cystitis (8.47% vs. 7.64%, p=0.761), and grade 3-4 toxicities. Conclusions: The combination of Nimotuzumab and CCRT for LACC has a better reduction rate of lesions and ORR, without increasing side effects. [Table: see text]
Clinico-molecular predictors of exceptional response to immune checkpoint inhibitors (ICI) in metastatic cervical cancer (mCC).
Authors: Barraud Solenn , Roussel-Simonin Cyril , Leary Alexandra 
Published: June 2024

5539 Background: Metastatic cervical cancer (mCC) constitutes a global health challenge, despite preventive efforts like HPV vaccination, with imputable 342,000 deaths in 2020. Immunotherapies with Immune checkpoint inhibitors (ICI) have been assessed in the context of recurrent or mCC. Only 15% of patients with PDL1+ mCC respond to ICI, however responses can be prolonged. We aimed to describe outcomes for long-term responders (LTR) versus non long-term responders (NLTR) to ICI, and identify clinico-molecular predictors for LTR. Methods: We conducted a retrospective review of all patients with mCC treated with an ICI at Institut Gustave Roussy (IGR). Patients were classified as LTR if they had a complete response (CR) / partial response (PR) / stable disease (SD) maintained for ≥12 months (mo) and as NLTR if progressed <12mo after ICI initiation. Cox regression analysis was performed to identify factors significantly associated with LTR (vs NLTR) and expressed as an odds ratio (OR). For a subset (43/106 patients), genomic analyses were performed using large panel next generation sequencing done at IGR within specific trials: STARTRK (NCT02097810) and STING (NCT04932525) on a tumor sample. Results: Between 01/2015 and 09/2023, 106 patients with mCC were treated with an ICI at the IGR. 20 patients (19%) were classified as LTR and 86 as NLTR (81%). 93% of patients received ICI without chemotherapy (2 LTR and 6 NLTR). After a median follow-up of 42mo, median PFS was not-reached in LTR versus 3.5mo for NLTR. Among the 20 LTR, 11 pts were in sustained complete response with a median of 22mo (range 2-55mo) since ICI discontinuation. Neither body mass index, performance status, LDH, neutrophil/lymphocyte ratio nor number of prior lines were predictive of LTR vs NLTR. A multivariate regression analysis identified 3 clinical factors significantly associated with LTR: oligo-metastatic (OR=11.4; p 0.006), lymph node metastases only (OR=8.2; p 0.02) and progression outside of irradiated fields (OR=5.9; p 0.03). With regards to molecular features, neither TMB nor MMR status were predictive, however PIK3CA mutations were significantly more frequent in LTR, found in 90% (vs 27% of NLTR) and PBMR1 mutations found exclusively in LTR, while NLTR presented with higher rates of STK11 alterations. Conclusions: Although responses to ICI in mCC remain rare (<20% patients), they are associated with impressive outcomes (median PFS>3.5 years) with a significant proportion disease-free months to years after ICI discontinuation suggesting some may be cured. Certain clinico-molecular features are strongly associated with LTR and may allow the selection of patients for ICI.
Safety and tolerability of durvalumab + carboplatin/paclitaxel followed by durvalumab ± olaparib in patients with newly diagnosed advanced or recurrent endometrial cancer (EC) in the DUO-E/GOG-3041/ENGOT-EN10 trial.
Authors: Thomes Pepin Jessica , Chon Hye Sook , Sundborg Michael J. , Gold Michael A. , Kim Byoung-Gie , Blank Stephanie V. , Liu Ji-Hong , McCollum Michael , Mori Masahiko , Moore Kathleen N. , Rivera Diaz Julian , de Padua Charles Andreé Joseph , Martínez-García Jerónimo , Papadimitriou Christos , Gri an Karin , Póka Róbert , Kowgier Matthew , Oscroft Emma , Van Nieuwenhuysen Els , Westin Shannon Neville 
Published: June 2024

5599 Background: DUO-E (NCT04269200) showed statistically significant and clinically meaningful progression-free survival improvement with addition of durvalumab (D) to carboplatin/paclitaxel (CP) followed by D ± olaparib (O) vs CP alone for patients (pts) with EC (Westin SN et al. J Clin Oncol 2024;42:283–99). We describe safety and tolerability, focusing on the most common adverse events (AEs). Methods: Pts with newly diagnosed FIGO Stage III/IV or recurrent EC and naïve to systemic treatment were randomized 1:1:1 to CP (CP + D placebo [pbo; 6 cycles] followed by D pbo + O pbo), CP+D (CP + D [1120 mg IV q3w; 6 cycles] followed by D [1500 mg IV q4w] + O pbo), or CP+D+O (CP + D [6 cycles] followed by D + O [300 mg tablets bid]). Safety was assessed through AEs. Results: 709 pts (19.3% mismatch repair deficient [dMMR], 80.7% MMR proficient [pMMR]) received treatment (CP: n=236; CP+D: n=235; CP+D+O: n=238). Total median treatment duration with D/pbo was 9.0, 9.9 and 13.1 months in the CP, CP+D and CP+D+O arms and 5.7, 7.6 and 9.2 months withO/pbo, respectively. 18.6%, 20.9% and 24.4% of pts in the CP, CP+D and CP+D+O arm, respectively, had AEs leading to treatment discontinuations, 50.0%, 54.5% and 68.9% had AEs leading to dose interruptions, and 56.4%, 54.9% and 67.2% had grade ≥3 AEs. There was no increase in immune-mediated AEs or AEs of special interest for O with CP+D+O. There were 3 cases of pure red-cell aplasia with CP+D+O (all grade 3) and 3 of autoimmune hemolytic anemia (1 with CP+D, 2 with CP+D+O; all grade 3). The most common AEs were mostly low grade, with grade 3/4 in few pts (anemia [14%, 16%, 24% in the CP, CP+D, CP+D+O arms, respectively], alopecia [0%, 0%, 0%], nausea [1%, <1%, 3%], fatigue [2%, 2%, 2%]), and led to few treatment discontinuations and interruptions (Table). AE profiles were generally consistent across MMR subgroups. Conclusions: In DUO-E, safety findings were generally consistent with the known safety profiles of CP, D and O. The addition of D to CP followed by D or by D + O resulted in expected and manageable safety profiles compared with CP alone, with the most common AEs being low grade and leading to few discontinuations or dose modifications/interruptions of D/pbo or O/pbo. Clinical trial information: NCT04269200 . [Table: see text]
Real-world treatment patterns and outcomes by mismatch repair/microsatellite instability (MMR/MSI) status in patients (pts) with advanced endometrial cancer (aEC), 2018-2023.
Authors: Pothuri Bhavana , Thaker Premal H. , Tymejczyk Olga , Reiss Samantha , Nitti Giovanni , Cain Theresa , Hada Manila 
Published: June 2024

5601 Background: Over the past decade, progress has been made in treating aEC, with newer therapies introduced in the first-line (1L) and second-line (2L) setting. Molecular profiling of MMR/MSI has emerged as a valuable tool for guiding treatment decisions, but real-world evidence on the shifting treatment paradigm is limited. Thus, this study aims to assess molecular profiling uptake, treatment patterns, and outcomes among aEC pts. Methods: This retrospective study included pts from the nationwide Flatiron Health electronic health record-derived deidentified database who were diagnosed with aEC (stage III/IV or recurrent) and initiated 1L therapy between 1/1/2018 and 6/30/2023. Patient characteristics, treatment patterns, and real-world time to next treatment (rwTTNT) were examined across MMR/MSI status: deficient (dMMR), proficient (pMMR), and never tested (NT). Kaplan-Meier methods were used to generate unadjusted time to event estimates. Results: A total of 1,441 pts met study criteria. Median age at aEC diagnosis was 68 years (range: 26-85), 1,056 (73%) were treated in the community setting, and 1,199 (83%) received MMR/MSI testing. Endometrioid carcinoma occurred in 619 (43%) overall and was the predominant histology (231/293; 79%) in dMMR. Approximately 15% had record of another cancer diagnosis at any point. NT pts were more likely than those tested to be Black or African American (26% vs 18%) and diagnosed with stage IV disease (55% vs 48%). The table presents select therapies and rwTTNT estimates. pMMR pts often received platinum-based chemotherapy (PBCtx) in 1L (67%) and immune checkpoint inhibitor (CPI) + vascular endothelial growth factor (VEGF) inhibitor therapies in 2L (23%), while dMMR pts were more likely than others to receive other CPI regimens (mono, combo + chemo) in 1L (23%) and 2L (44%). Median rwTTNT was similar across subgroups in 1L but was markedly longer among dMMR pts (10.8 vs 5-6 months) in 2L. Conclusions: While MMR/MSI testing was common, use of 2L immunotherapy for dMMR (51%) and CPI + VEGF for pMMR (23%) was lower than expected and may reflect slow uptake of recently approved, molecular profile-specific therapies. MMR/MSI testing gaps remain, especially in underrepresented pts, and may be a barrier to adoption of new therapies. Future analyses will be critical to assess changes in outcomes over a longer timeframe. Continued education is needed to increase access to newer FDA approved treatments. [Table: see text]
Prognostic value of PORTEC-3 molecular markers by disease risk in a real-world early endometrial cancer cohort.
Authors: Dow Jessica , Kolli Sahiti , Karalius Brad , Shami Jessica , Khosla Sajan , Roy David , Mayer Ingrid A. , Dempster Sara 
Published: June 2024

5604 Background: Molecular classification of endometrial cancer (EC) proposed by The Cancer Genome Atlas in 2013 has improved prognostic assessment of patients. PORTEC-3 assessed these molecular markers in early-stage high risk patients. We examine the prognostic value of these markers in a real-world data (RWD) cohort of early-stage high risk patients and extend the analysis to intermediate and low risk patients to inform treatment decisions across disease risk levels. Methods: We performed a retrospective study (2016-2022) of EC patients from the Tempus de-identified, multimodal RW database. Stage I-III patients who received total hysterectomy with bilateral salpingo-oophorectomy and next generation sequencing (NGS) Tempus xT assays were stratified into high, intermediate, and low risk disease levels based on tumor characterization and categorized into POLE mutated (POLEm), mismatch repair-deficient (dMMR), p53-abnormal (p53abn), or no specific molecular profile (NSMP) PORTEC-3 subtypes. Recurrence-free survival (RFS), defined as time from surgery to earliest disease recurrence, progression, metastasis or death, was assessed using Kaplan-Meier methods for the combination of risk level and molecular subtype. We compared RFS trends across molecular subtypes at 5-years in PORTEC-3 and 18-months in RWD due to limited follow-up. Results: Of the 740 eligible RWD patients, 546 (74%), 110 (15%) and 84 (11%) were high, intermediate, and low risk and 286 (39%), 250 (34%), 180 (24%) and 24 (3%) were P53abn, NSMP, dMMR and POLEm, respectively. Similar to RFS trends at 5 years in PORTEC-3, the p53abn subtype consistently had the lowest 18-month RFS, although the degree of separation from other subtypes varied across risk levels. NSMP and dMMR subtypes had 18-month RFS within 4% of each other for high and low risk levels, consistent with PORTEC-3. The POLEm subtype had 100% 18-month RFS across risk levels, but low prevalence. Conclusions: Marker prognostic ranking was consistent between the PORTEC-3 high risk cohort and all risk levels in RWD despite absolute RFS differences likely due to differences in baseline characteristics and outcome assessments. The consistent poor prognosis of p53abn patients, good prognosis of POLEm albeit with limited power, and moderate prognosis of NSMP and dMMR patients in RWD support use of these markers to inform treatment decisions across disease risk levels in an early EC setting. [Table: see text]
HER2 expression in a molecularly characterized cohort of patients with endometrial cancer (EC): SPECTRUM study.
Authors: Cortés Salgado Alfonso , Moreno Esther , Palacios José , Guerra Eva , del Campo-Albendea Laura , Carretero-Barrio Irene , Rosas Marta , Saavedra Serrano Cristina , Gion Maria , Caniego-Casas Tamara , Fernández-Abad María , Lopez Miranda Elena , Martinez-Jañez Noelia , Vida Navas Elena , Pérez Míes Belén 
Published: June 2024

5610 Background: Human epidermal growth factor receptor 2 (HER2)-low is a new category defined by HER2 1+ or 2+ by immunohistochemistry (IHC) and lack of HER2 amplification by in situ hybridization (ISH). Trastuzumab deruxtecan demonstrated antitumor activity in HER2-expressing gynecologic tumors. Little is known about HER2-low frequency in EC subtypes, the heterogeneity of the expression, the best scoring criteria or the prognostic value. Methods: This is a single center, retrospective study including patients diagnosed with EC amenable to curative treatment from 2003 to 2019. Two tissue cores of each sample were selected for the creation of 5 tissue microarrays (TMA). Molecular subrogated (MS) classification (WHO 5ed) was performed: polymerase epsilonmutated (POLEmut), mismatch repair deficient (dMMR), TP53 abnormal (p53abn) or non-specific molecular profile (NSMP). HER2 was assessed by IHC (4B5) and ISH on TMAs. HER2 scoring was done according to ASCO/CAP guidelines for breast and the proposed endometrial criteria. HER2 heterogeneity was defined as a difference in HER2 IHC ≥2+ or discrepancy in HER2 ISH between cores. Primary objective was to describe the frequency of HER2-low in MS. Secondary objectives included to assess heterogeneity, concordance between breast and endometrial criteria and the impact of HER2-low on recurrence-free (RFS) and overall survival (OS). Results: 193 patients were analyzed. Median age was 66.4 years (31-90). According to FIGO 2009 classification, stage I, II and III-IV corresponded to 71.5%, 14% and 14.5% of patients. Most cases (57.5%) were low-grade endometrioid followed by 14% serous, 11.9% high-grade endometrioid, 5.2% clear cell, 2.6% carcinosarcoma and 8.7% other histology. Regarding MS, 3.1% were POLEmut, 25.4% dMMR, 28% p53abn, 40.9% NSMP and 2.6% unclassifiable. Considering the entire cohort, 69.9% were HER2-negative (0+), 25.8% HER2-low and 4.3% HER2-positive (3+ or ISH+). The frequency of HER2-low was highest for POLEmut (66.7%) followed by p53abn (42.6%) (Table). Low heterogeneity in HER2 expression was demonstrated, with an agreement between cores in 84.5% of cases. Breast and endometrial criteria showed concordance in 85.5% of patients, with a kappa of 0,624 (p<0,05). HER2-low nor HER2-positive versus HER2-negative had an impact on RFS or OS. Conclusions: This is the first study showing the spectrum of HER2 expression in a MS cohort of EC. HER2-low is more frequent in POLEmut and p53abn subtypes. HER2-low had no prognostic significance. [Table: see text]