tbuckley/cabot-search huggingface dataset:
Intratumoral Ral-binding protein 1 (RalBP1) expression as a potential predictor of bevacizumab treatment efficacy in patients with ovarian cancer.
Authors: Fabian Bernhard Thaddäus Kraus, Christina Schramm, Doris Mayr, Anca Chelariu-Raicu, Juliane Reichenbach, Nicole Elisabeth Topalov, Christina Viktoria Tauber, Alexander Burges, Mirjana Kessler, Sven Mahner, Fabian Trillsch, Bastian Czogalla
Journal: Journal of Clinical Oncology (2024)

5576 Background: The anti-VEGF antibody bevacizumab (Bev) has become part of the first-line treatment of patients with advanced ovarian cancer (OC) due to its significant impact on progression-free survival (PFS). However, a significant effect on overall survival (OS) was not demonstrated. In this context, we hypothesized that the stress-responsive multidrug transporter and modulator of neovascularization Ral-binding protein 1 (RalBP1) might be prognostic for patient survival and stratify patients according to their predicted Bev response. Methods: Tissue samples from 554 patients with epithelial OC were obtained during first-line cytoreductive surgery at the Department of Obstetrics and Gynecology, University Hospital, LMU Munich, between 2003 and 2021. RalBP1 immunohistochemical staining was quantified using a mean staining intensity score (MSIS, 1-3) and a cut-off was defined as 2.5. Correlationbetween MSIS and clinicopathologic data was assessed using two-sample t-tests. Additional correlation measures included Spearman’s correlation, Chi 2 -test and ANOVA. PFS and OS were visualized by Kaplan-Meier curves and significant differences determined by Wilcoxon. Cox regression models were used for multivariate analysis. Results: RalBP1 was present in the cytosol of almost all OC cells (RalBP1-low: n= 385, RalBP1-high: n= 169) and independent of histopathologic subtype or grading. Patients with elevated intratumoral RalBP1 expression showed significantly improved median PFS (73.5 vs. 35.8 months, HR=0.62, p=0.033) and median OS (120.1 vs. 71.7 months, HR=0.56, p=0.007) after complete tumor debulking and platin-based adjuvant chemotherapy (n=155). In a comprehensive multivariate analysis, RalBP1 expression levels emerged as an independent prognostic marker for both OS (HR=0.67, p=0.031) and PFS (HR=0.72, p=0.033). Interestingly, in the subgroup of all patients that received an adjuvant platinum-based chemotherapy (n=351), the RalBP1–low patient status was shown to be a predictive factor for response to Bev therapy for both PFS (median 26.4 vs. 18.1 months, HR=0.94, p=0.036) and OS (median 63.4 vs. 49.3 months, HR=0.72, p=0.041). Conclusions: RALBP1 may serve as a prognostic biomarker for OC patients, helping to identify those who are likely to benefit not only in PFS but also in OS following Bev therapy. Its tumor biological role remains a matter of current investigations.
Systematic review of frailty assessment in ovarian cancer studies.
Authors: Ainhoa Madariaga, Husam Alqaisi, Alicia Castelo, Rouhi Fazelzad, Stephanie Lheureux, Amit M. Oza
Journal: Journal of Clinical Oncology (2024)

5564 Background: Frailty is a state of vulnerability to poor resolution of homeostasis following a stressor event, such as chemotherapy or surgery. Better knowledge of frailty assessments (FA) in ovarian cancer could help drive a global and individualized care strategy. Methods: A search was performed in 10 databases including Medline, Embase and Cochrane (up to March 2022). The search strategy utilized a combination of keywords and controlled vocabulary related to ovarian cancer, frailty/geriatric assessment. Studies performing FA in patients with ovarian cancer on systemic therapy, surgery and surveillance were included. The 2020 PRISMA checklists were followed, and the study was registered in PROSPERO (CRD42022323409). Primary objective was to identify frailty scales used in ovarian cancer studies. Secondary objectives were to describe impact of results on decision making and outcomes, adherence to ASCO Vulnerability Assessment (VA) guidelines. Results: 2,259 articles were screened, and 48 included in the final analysis. Studies were published between 2004-2022 and included 84,575 patients. 23 studies (48%) had an age limit for inclusion (≥65 to ≥80 years). Six studies were interventional (1 phase 3 clinical trial [CT], rest phase 2) and 42 were observational (45% retrospective). FA were highly variable. Median number of tests to assess frailty were 3 (range 1-13). Most studies used a combination of tests (several may apply): validated frailty scales (21 studies, 43.7%), nutritional/sarcopenia status (20 studies, 41.7%), functionality/physical performance (19 studies, 39.6%), geriatric assessment (7 studies, 14.6%). Global measures with all the comprehensive assessment items of the ASCO VA guideline were included in 14.6% of studies. FA was not used for decision making in any study. One FA designed for ovarian cancer was identified, the GINECO Geriatric Vulnerability score. Frailty was the primary objective in 26 studies (54%), out of which 12 were retrospective. Among them, study objectives were highly variable including survival, complications, or cost of surgery (13 studies) and systemic therapy (7 studies), prognosis (4 studies), treatment compliance and dependence (1 each). All but one (a prognostic study) met its primary outcome demonstrating worse outcomes in frail patients. Conclusions: Frailty assessments are heterogeneous in ovarian cancer studies. Most studies do not adhere to the ASCO vulnerability assessment guidelines. An association between frailty and poor outcomes was detected in surgical and systemic therapy studies. There is room for improvement, as none of the assessed studies used the frailty for decision making.[Table: see text]
Efficacy, safety, and biomarkers of neoadjuvant niraparib monotherapy in homologous recombination deficiency (HRD) advanced ovarian cancer: A prospective, multicenter, phase II, single-arm NANT study.
Authors: Qing-lei Gao, Dan Liu, Huayi Li, Wei Zhang, Ping Wang, Jundong Li, Wanying Shan, Ronghua Liu, Gang Chen, Mingfu Wu, Xiao Li, Cheng Liu, Rutie Yin, Shengtao Zhou, MaoMao Li, Shanyang He, Guangnian Zhao, Kun Song, Li Hong, Ding Ma
Journal: Journal of Clinical Oncology (2024)

5549 Background: The efficacy of PARP inhibitors as neoadjuvant therapy and its clear association with tumor microenvironment (TME) status remain enigmatic. Here, for the first time, we reported the efficacy and safety of niraparib monotherapy, an oral low-toxicity PARP inhibitor, as the neoadjuvant therapy in patients (pts) with HRD high-grade serous ovarian cancer (HGSOC), and directly linked pre-treatment TME components with response using cutting-edge technologies. Methods: Treatment-naïve pts with newly diagnosed advanced unresectable HGSOC and those who could not endure primary debulking surgery were enrolled to receive laparoscopic biopsies. TME landscape was profiled by single-cell RNA sequencing and multiplex immunohistochemistry. Pts with HRD ( BRCA1/2 mutations and/or genomic instability score ≥ 42) HGSOC received daily oral niraparib for two 28-day cycles. Pts with complete response, partial response (PR), or stable disease (SD) received interval debulking surgery (IDS). The co-primary endpoints were objective response rate (ORR) and R0 resection rate. Results: Between January 18, 2021 and July 18, 2023, 127 pts from six centers were screened for eligibility. Totally, 67 HRD pts received neoadjuvant niraparib monotherapy, 48 pts completed response evaluations, and 40 pts underwent IDS. Thirty pts achieved PR and 12 pts reached SD, resulting in an ORR of 62.5% and a disease control rate (DCR) of 87.5%. BRCAm pts exhibited improved responses with increased ORR (77.3%) and DCR (100.0%). For surgical outcomes, 80.0% of pts achieved R0 resection and 95.0% of pts accomplished optimal debulking. Treatment-related adverse events (TRAEs) of grade ≥3 were observed in 61.2% of pts and hematological toxicities were the most common. No fatal TRAEs were reported. Co-enrichment of MRC1 + macrophages, effector regulatory T cells, and myofibroblastic cancer-associated fibroblasts were associated with lack of response. Conclusions: Neoadjuvant niraparib monotherapy regimen achieved encouraging ORR and R0 resection rate with tolerable toxicities in pts with HRD unresectable HGSOC, offering an alternative option for those pts unwilling to receive or unable to tolerate neoadjuvant chemotherapy. Pre-treatment TME factors were correlated with clinical response to PARP inhibitors. Clinical trial information: NCT04507841 . [Table: see text]
Scalp Cooling in Preventing Persistent Chemotherapy-Induced Alopecia: A Randomized Controlled Trial
Authors: Danbee Kang, Juhee Cho, Di Zhao, Jeonghyun Kim, Nayeon Kim, Hoyoung Kim, Sooyeon Kim, Ji-Yeon Kim, Yeon Hee Park, Young Hyuck Im, Eliseo Guallar, Jin Seok Ahn
Journal: Journal of Clinical Oncology (2024)

PURPOSE Current studies of the efficacy of scalp cooling are limited by short-term duration. Therefore, we conducted a randomized controlled trial to evaluate the efficacy of scalp cooling in reducing persistent chemotherapy-induced alopecia (PCIA) 6 months after chemotherapy. METHODS We conducted an open-label randomized controlled trial comparing scalp cooling versus control in newly diagnosed patients with breast cancer stages I-III scheduled to receive neoadjuvant or adjuvant chemotherapy with curative intent between December 2020 and August 2021. Patients were randomly assigned (2:1 ratio) to scalp cooling or usual clinical practice. The primary outcome was PCIA 6 months after chemotherapy. Hair thickness and density were measured using Folliscope 5.0. CIA-related distress was assessed using the CIA distress scale (CADS), with a higher score reflecting higher stress. RESULTS The proportion of patients with PCIA at 6 months was 13.5% (12/89) in the scalp-cooling group and 52.0% (26/50) in the control group. The average difference in the change in hair thickness from baseline between the scalp-cooling and control groups was 9.0 μm in favor of the intervention group. The average difference in the change in hair density between intervention and control at the end of the study was –3.3 hairs/cm 2 . At 6 months after chemotherapy, the average difference in the change in CADS score between the intervention and control groups was –3.2 points, reflecting reduced CIA-related stress in the intervention group. CONCLUSION Scalp cooling reduced the incidence of PCIA, primarily by increasing hair thickness compared with control. Scalp cooling is helpful in promoting qualitative hair regrowth. Yet, further research is necessary to observe longer-term benefits of scalp cooling.
Benmelstobart (TQB2450) combined with anlotinib hydrochloride capsule in the treatment of advanced, recurrent, or metastatic endometrial cancer: A multicohort, open label, multicenter, phase II clinical trial (TQB2450-II-08).
Authors: Xiaohua Wu, Xiaojun Chen, Ke Wang, Dong Wang, Ruifang An, Jianqing Hou, Ying Yang, Danbo Wang, Pengpeng Qu, Bingzhong Zhang, Wei Duan, Xiumin Li, Ai-min Zang, Guohua Yu, Hanmei Lou, Desheng Yao, Shuzhen Wang, Dong Yan, Liang Li, Xiaowei Liu
Journal: Journal of Clinical Oncology (2024)

5593 Background: The treatment options after first-line chemotherapy for endometrial cancer (EC) are very limited. Several immune checkpoint inhibitors or combined with antiangiogenic drugs have shown antitumor activity and been approved in EC. Anlotinib is a multiple-targeted tyrosine kinase inhibitor that has been approved for the treatment of several solid tumors. Benmelstobart (TQB2450) is a humanized monoclonal antibody targeting programmed death-ligand 1 (PD-L1). This multicohort, open label, multicenter, phase II study aims to evaluate the efficacy and safety of TQB2450 injection or combined with anlotinib hydrochloride capsule in the treatment of recurrent or metastatic advanced EC. Methods: Patients with pathologically confirmed recurrent or metastatic advanced EC failed at 1 or 2 prior lines of therapy will be enrolled. Non-MSI-H/dMMR patients were treated with TQB2450+anlotinib therapy (TQB2450 1200mg, IV D1/Q3W; anlotinib 12mg PO QD, D1-14/Q3W) (cohort 1) or anlotinib (cohort 3), MSI-H/dMMR patients were treated with TQB2450 (cohort 2), until disease progression or intolerable toxicity experienced. Cohort 1 is divided into two stages for enrollment. In the first stage, 22 patients are enrolled. If the lower limit of the confidence interval is greater than 15%, indicating that there are at least 8 patients achieved CR/PR, consideration can be given to proceeding to the next stage. In the second stage, 85 patients are enrolled. The primary endpoint was the objective response rate (ORR) by independent review committee (IRC). Key secondary endpoints include ORR by investigator, disease control rate (DCR), duration of response (DoR), progression free survival (PFS), overall survival (OS) and safety. Results: As of November 09, 2023, 170 patients were enrolled and treated (cohort 1 N=107, cohort 2 N=32, cohort 3 N=31). In the first stage, 22 patients enrolled, 8 achieved CR/PR, and the study progressed to the second stage in cohort 1. Antitumor activities are shown in the table. Treatment-emergent adverse events (TEAEs) occurred in 99.07%, 100% and 100% of patients. Grade ≥3 TEAEs were reported in 74.77%, 40.63% and 87.10% of patients, respectively, with the most common ones being weight loss (46.73%, 25%, 29.03%), white blood cell decreased(47.66%, 12.5%, 19.35%), blood corticotrophin increased (44.86%, 15.63%, 22.58%), thyroid stimulating hormone increased (37.38%, 3.13%, 25.81%). Conclusions: TQB2450 plus anlotinib showed promising antitumor activity with a manageable safety profile in the treatment of recurrent or metastatic advanced EC. Clinical trial information: NCT04574284 . [Table: see text]
HER2 expression in a molecularly characterized cohort of patients with endometrial cancer (EC): SPECTRUM study.
Authors: Alfonso Cortés Salgado, Esther Moreno, José Palacios, Eva Guerra, Laura del Campo-Albendea, Irene Carretero-Barrio, Marta Rosas, Cristina Saavedra Serrano, Maria Gion, Tamara Caniego-Casas, María Fernández-Abad, Elena Lopez Miranda, Noelia Martinez-Jañez, Elena Vida Navas, Belén Pérez Míes
Journal: Journal of Clinical Oncology (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&lt;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]
Anlotinib plus hormone therapy in patients with platinum-resistant recurrent ovarian cancer: A prospective, single-arm, open-label, phase II study.
Authors: Xipeng Wang, Jiarui Li, Ping Zhang, Yizhi Wang, Xin Lu, Hong Xu
Journal: Journal of Clinical Oncology (2024)

5567 Background: Studies have suggested that estrogen regulates the malignant transformation of ovarian surface epithelial cells, stimulates the growth and migration of cancer cells. and promotes the VEGF expression in epithelial ovarian cancer. Anlotinib is a novel multi-target tyrosine kinase inhibitor, inhibiting tumor angiogenesis and proliferative signaling. In this study, we evaluate the activity of anlotinib combined with letrozole in patients with estrogen receptor positive, platinum-resistant recurrent ovarian carcinoma (NCT04720807). Methods: Patients who have previously received two or more chemotherapy treatments, with histopathologically confirmed high-grade serous ovarian cancer (including salpingo carcinoma and peritoneal carcinoma), estrogen receptor (ER) positive and ECOG 0-2 were considered eligible for enrollment. Anlotinib was taken orally (10mg mg qd, d1-14, 21 days per cycle), and letrozole was taken orally (2.5mg qd, d1-21, 21 days per cycle). The treatment was continued until disease progression, death, or intolerant toxicity. The primary endpoint was objective response rate (ORR) and the secondary endpoints included disease control rate (DCR), duration of remission (DOR) progression free survival (PFS), overall survival (OS) and safety. Results: Between September 2020 and December 2023, 30 patients with a median age of 61 years (range:50-79), FIGO histopathological stage I (11.1%), Ⅱ(3.7%), III (59.3%) and IV (25.9%) were enrolled. Twenty-seven of these patients have been evaluated for efficacy. In the efficacy-evaluable population (n=12), the therapeutic evaluation showed that 7 and 13 patients achieved partial response and Stable disease respectively(with the standards of GCIC), yielding the ORR of 16.7% (7/27 95% CI: 11.8% to 46.6%). The DCR was 74.1% (20/27, 95% CI: 53.4% to 88.1%). The median PFS was 4.24 months (95% CI: 3.71m to 5.09m) and the median OS was 18.96 months (95% CI: 8.34m to 31.05m).With subgroup analyses, Patients who had received PARPi before and patients with baseline CA125 level &gt;500 had significant prolongations in mOS and mPFS, respectively. The most common adverse events (AEs) were grade 1 or 2, which included laryngitis (44.4%), stomatitis (37.0%), hand-foot syndrome (29.6%), and fatigue (25.9%), diarrhea (22.2%), hypertension (14.8%),. The grade 3 AEs were hypertension (37.0%), hand-foot syndrome (3.7%), diarrhea (3.7%) and hyperuricemia (3.7%). No higher AEs or treatment-related death were observed. Conclusions: As a chemo-free regimens, anlotinib plus letrozole showed a promising efficacy with a favorable toxicity profile for patients with platinum-resistant recurrent ovarian cancer. Research Sponsor: Chia Tai Tianqing Pharmaceutical Group Co. GYNECOLOGIC CANCER. Clinical trial information: NCT04720807 .
Efficacy and safety of sintilimab plus paclitaxel and cisplatin as neoadjuvant therapy for locally advanced cervical cancer: A phase II trial.
Authors: Ting Wan, He Huang, Yanling Feng, Jundong Li, Min Zheng, Yifan Meng, Jihong Liu
Journal: Journal of Clinical Oncology (2024)

5512 Background: The KEYNOTE 826 study has demonstrated significant survival benefits with first-line pembrolizumab (anti PD-1) plus chemotherapy for recurrent/metastatic cervical cancer (CC). This phase II study aims to evaluate the efficacy and safety of Sintilimab (anti PD-1) plus paclitaxel and cisplatin as neoadjuvant therapy for locally advanced CC. Methods: Patients with newly confirmed locally advanced CC (stage IB3 or IIA2) received neoadjuvant chemotherapy with paclitaxel (150mg/m2, iv) and cisplatin (70mg/m2, iv) plus Sintilimab (200mg, iv) Q3W for 3 cycles, followed by radical surgery. The patients evaluated PD without distant metastases after 2 cycles of neoadjuvant therapy underwent surgery immediately. The primary endpoint was pathological complete remission rate (pCR). Secondary endpoints included ORR, PFS, 2-years PFS rate and adverse events (CTCAE 5.0) and biomarker exploration. Results: As of data cutoff on Feb 1st, 2024, 47 eligible patients were enrolled, 44 patients received 3 cycles of neoadjuvant therapy, 43 patients then underwent radical surgery and were evaluable. The primary endpoint of pCR rate was 32.6% (14/43), optimal remission rate (residual tumor cells with a depth of less than 3mm) was 51.2% (22/43). Except for one patient with SD, 42 had objective responses (97.7%). At the date cutoff, the median follow-up time was 17 months (range 1-35), two patients who evaluated as PR after neoadjuvant therapy were recurred, one with distant lymph node recurrence, and the other with lung metastasis. In terms of hematological toxicity, 15 patients presented with grade 3-4 neutropenia and no other grade 3-4 adverse events. Possible immune-related side effects included skin rash (17/47, G1-2), alanine aminotransferase increased (8/47, G1), hypothyroidism (6/47, G1-2), creatinine increased (5/47, G1), and hyperlipidemia (1/47, G1). Conclusions: Sintilimab plus paclitaxel and cisplatin as neoadjuvant therapy showed encouraging antitumor activity with 32.6% pCR rate and manageable toxicities in patients with locally advanced CC. Clinical trial information: NCT04799639 .