tbuckley/cabot-search huggingface dataset:
Differences in physical and emotional distress amongst patients undergoing neoadjuvant chemotherapy versus surgery for advanced ovarian cancer: Patient-reported outcomes at diagnosis.
Authors: Shilpa Mokshagundam, Michaela E McGree, Angela J Fought, Karen P Ishitani, Minji K Lee, Amanika Kumar
Journal: Journal of Clinical Oncology (2024)

5546 Background: Advanced ovarian cancer (OC) is managed with cytoreductive surgery and platinum-based chemotherapy. Prehabilitation is a multimodal intervention to improve physical and mental health prior to oncologic surgery. This study evaluates baseline differences in clinical characteristics, functional status, and patient-reported outcomes (PROs) between patients undergoing primary cytoreductive surgery (PCS) versus neoadjuvant chemotherapy (NACT) who enrolled in a prospective prehabilitation trial. Methods: This was a single-institution, non-randomized prospective behavioral intervention trial of patients with suspected advanced stage (IIIC/IV) OC. Baseline functional testing included the Short Physical Performance Battery (SPPB), Fried Frailty Index (FFI), gait speed, and grip strength. Patient-Reported Outcomes Measurement Information System (PROMIS) metrics, the Mindfulness Attention Awareness Scale (MAAS), and the Perceived Stress Scale (PSS-10) were used to evaluate PROs. Comparisons between cohorts utilized two-sample t-test or Kruskal Wallis test for continuous variables and chi-square or Fisher’s exact test for categorical variables. T-scores were obtained for PROMIS data using the HealthMeasures Scoring Service; validated cut points for PROMIS, MAAS, and PSS-10 were used for categorization. Results: Amongst the 53 enrolled patients, physical and emotional distress was higher amongst OC patients compared to population means. When compared to PCS patients, NACT patients were more likely to report “severe” in at least one PROMIS domain (emotional distress and anxiety, pain interference, physical function, and fatigue, p&lt;0.01). NACT patients reported significantly higher levels of perceived stress (p&lt;0.01). NACT patients were more likely to have stage IV disease, albumin &lt;3.5 g/dL, and lower gait speed and grip strength (all p&lt;0.01). Despite differences in clinical variables and PROs including physical function, there were no measurable differences in physical function based on SPPB and FFI. Conclusions: Advanced OC patients have high psychosocial needs, with NACT patients reporting severe perceived symptoms on PRO measures. The PSS-10 may be a valuable screening tool for patients undergoing NACT to prioritize supportive care services. Clinical trial information: NCT05047926 . [Table: see text]
Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy and in combination with abemaciclib, in endometrioid endometrial cancer (EEC): Results from the EMBER phase 1a/1b study.
Authors: Kan Yonemori, Kalyan Banda, Valentina Boni, Joohyuk Sohn, Tarek Meniawy, Janine Margaret Lombard, Peter A. Kaufman, Debra L. Richardson, Laura Bender Somme, Koji Matsumoto, Karthik Giridhar, Jose Angel Garcia Saenz, Hans Prenen, Bernard Doger de Spéville Uribe, Don S. Dizon, Javier García-Corbacho, Yujia Li, Bastien Nguyen, Roohi Ismail-Khan, Patrick Neven
Journal: Journal of Clinical Oncology (2024)

5589 Background: Imlunestrant is a next-generation oral SERD designed to deliver continuous estrogen receptor (ER) target inhibition aimed to improve outcomes for patients (pts) with ER+ cancers. In the first-in-human Phase 1a/1b EMBER trial (NCT04188548), imlunestrant showed favorable safety, pharmacokinetics, and clinical benefit in pre-treated pts with ER+ advanced breast cancer or EEC. Here, we report updated imlunestrant monotherapy data and the first clinical data of imlunestrant + abemaciclib in ER+ EEC pts from EMBER. Methods: Eligible pts had ER+ EEC previously treated with (or deemed inappropriate for) platinum-containing chemotherapy. Prior fulvestrant or aromatase inhibitor therapy was not allowed. In Phase 1a, pts received imlunestrant alone, and in Phase 1b, pts were randomized (1:1) to imlunestrant alone or with abemaciclib. Plasma samples were collected at baseline (all pts) and at cycle 2 (monotherapy pts) for ctDNA analysis (Guardant 360 assay) to correlate with clinical benefit. Primary endpoints were RP2D of imlunestrant monotherapy and in combination. Secondary endpoints included safety, tolerability, and overall response rate (ORR), clinical benefit rate (CBR: complete or partial response, or stable disease ≥24 weeks), and progression-free survival (PFS) using RECIST v1.1. Results: Overall, 72 pts were treated; 39 pts received monotherapy (33 at 400mg [RP2D] and 6 at 800mg po daily) and 33 pts received imlunestrant (29 at 400mg and 4 at 800mg po daily) + abemaciclib (150mg po twice daily). Baseline characteristics, safety, and preliminary efficacy are presented (Table). For monotherapy, the most common TEAEs (all grade/grade 3) were nausea (36%/3%), diarrhea (26%/0), urinary tract infection (26%/3%), and abdominal pain (21%/8%). For imlunestrant + abemaciclib, the most common TEAEs (all grade/grade 3) were diarrhea (88%/3%), nausea (67%/0), fatigue (49%/9%) and anemia (46%/12%). In the monotherapy arm, pts with deeper (≥ 50%) declines in ctDNA variant allele frequency had a higher CBR (4/7 vs 4/17). Conclusions: Imlunestrant, as monotherapy or with abemaciclib, appears safe and tolerable with preliminary evidence of efficacy in pts with metastatic ER+ EEC. Clinical trial information: NCT04188548 . [Table: see text]
Real-world biomarker testing, treatment patterns and outcomes in a US cohort of patients with advanced ovarian cancer.
Authors: Dan Steven Veljovich, Richard T. Penson, Michael J. Birrer, Linlin Luo, Nick Pyrih, Simon Pack, Crystal Iu, Manila Hada
Journal: Journal of Clinical Oncology (2024)

5571 Background: Olaparib, a poly(ADP-ribose) polymerase inhibitor (PARPi), has shown efficacy as monotherapy for the treatment of BRCA mutated (BRCAm) advanced ovarian cancer (AOC) and in combination with bevacizumab for Homologous Recombination Deficient (HRD+) AOC. This study describes real-world (RW) characteristics, testing and treatment patterns in patients (pts) with AOC, including outcomes with olaparib first-line maintenance (1LM) therapy. Methods: A retrospective observational study utilizing the electronic health record-derived de-identified US-based Flatiron Health database was performed including women aged ≥18 y at AOC diagnosis (Jul 2018–Dec 2022) with ≥1 clinical visit. Pts were followed from diagnosis until Aug 31, 2023, cessation of dataset coverage, or death, whichever occurred first. Biomarker testing was defined as evidence of a test for BRCAm or HRD (inclusive of BRCAm). Estimated RW time to first subsequent therapy or death (TFST) and time to treatment discontinuation or death (TTD) are reported. Results: Demographic and clinical characteristics are shown in the Table. Of 1503 pts included, 80.8% (n=1214) were BRCAm tested and 36.3% (n=546) were HRD (inclusive of BRCAm) tested. Among pts who were either BRCAm or HRD tested (n=1220), 58.0% (n=708) were tested between AOC diagnosis and initiation of 1LM therapy. No 1LM therapy was recorded in 61.9% (n=931/1503) of pts. In both BRCAm and HRD+ pts, olaparib, either as monotherapy (44.5% [n=69/155] and 33.6% [n=100/298], respectively) or in addition to bevacizumab (7.1% [n=11/155] and 9.4% [n=28/298], respectively), was the most frequently used PARPi for 1LM therapy (Table). Median (95% CI) TFST and TTD was 44.7 (27.0, NA) and 22.7 (17.0, 47.0) mos, respectively in BRCAm pts receiving olaparib 1LM (n=69), and 29.1 (22.1, NA) and 22.1 (13.1, NA) mos, respectively in HRD+ pts receiving olaparib + bevacizumab 1LM (n=28). Conclusions: While most pts received BRCAm testing, a majority did not receive HRD (inclusive of BRCAm) testing. A sizeable proportion of pts with actionable biomarker results did not receive PARPi as 1LM therapy highlighting the need for education on the importance of genetic testing to guide AOC treatment. Time-to-event outcomes were comparable with those from the SOLO1 and PAOLA-1 clinical trials, thus supporting the real-world effectiveness of olaparib. [Table: see text]
Germline genetic profiles of women with uterine cancer: A Myriad Collaborative Research Registry study.
Authors: Caitlin Ruth Johnson, Chinmayi Aryasomayajula, Alex Andrea Francoeur, Chelsea Stewart, Daniel Stuart Kapp, John K Chan
Journal: Journal of Clinical Oncology (2024)

5617 Background: To compare uterine cancer patient characteristics and genetic mutational profiles by age and self-identified ancestry. Methods: Data on uterine cancer patients who had germline, MyChoice, and/or Precise testing were collected from the Myriad Collaborative Research Registry. Mutations in genes of interest were obtained from TAPUR studies currently under enrollment. Graph Pad Prism v 10.1.1 was utilized for statistical calculations. Results: Of the 38,133 uterine cancer patients, 42.8% were diagnosed at &lt;50 years (younger) and 57.2% at ≥50 years (older). Approximately, 77.1% identified as Non-Hispanic White (NHW), 7.0% as Non-Hispanic Black (NHB), 2.2% as Hispanic, and 3.7% as Non-Hispanic Asian/Pacific Islander (NHAPI). Approximately 29.1% patients had germline Lynch gene mutations with 16.5%, 28.8%, 36.1%, and 18.4% occurring in MLH1, MSH2, MSH6, and PMS2, respectively (p&lt;0.001). Younger patients were more likely to have Lynch syndrome (9.6% vs 7.5%; p&lt;0.001) and MLH1 (1.2% vs 0.8%; p&lt;0.001) or MSH2 (3.1% vs 1.5%; p&lt;0.0001) mutations compared to older patients. Regarding race, MLH1 mutations were found in 5.2% of NHW and NHAPI, 4.9% of Hispanics, and 2.2% of NHB (p&lt;0.001). MSH2 mutations were most common among NHAPI (9.8%) and NHW (9.7%) followed by Hispanics (5.8%) and NHB (3.2%; p&lt;0.001). MSH6 mutations were most common in NHW (12.8%) vs Hispanics (6.5%), NHAPI (6.3%), or NHB (4.5%; p&lt;0.001). PMS2 mutations were highest among NHW (5.8%) followed by Hispanics (4.7%), NHAPI (4.4%), and NHB (2.9%; p=0.004). There were no differences in TMB (p=0.07), PDL1 (p=0.16), or MSI status (p=0.13) by age; however, younger patients had more HRD positivity (37.8% vs 30.9%; p&lt;0.0001) vs the older group. Regarding race, 50.0% of NHAPI, 36.9% of NHW, 30.8% of Hispanic, and 11.6% of NHB patients had high TMB (p=0.004). There were no significant differences in tumor HRD status (p=0.3), MSI status (p=0.3), or PDL1 positivity (p=0.4) by racial group. Additionally, 6.8%, 6.6%, 6.3%, and 4.4% of Hispanics, NHW, NHAPI, and NHB were BRCA positive. BRCA2 mutations were more present among Hispanics (4.2%) vs NHW (3.7%), NHAPI (3.4%), and NHB (2.3%; p=0.02). There were no differences in BRCA1 (p=0.3) or PTEN (p=0.8) mutations by racial group. Hispanic patients had the most germline p53 mutations (2.0%) followed by NHAPI (1.5%), NHW (1.4%), and NHB patients (0.7%; p=0.01). PDL-1 inhibitors may be useful among NHB based on germline POLE mutations (4.3%) vs NHW (1.2%), Hispanic (1.1%), and NHAPI patients (0.8%; p&lt;0.001). Conclusions: There are significant differences in germline testing results for women with uterine cancer by race/ethnicity and age, especially in Lynch genes which has implications for immunotherapy eligibility in the advanced and recurrent setting. Further work must be done to identify targetable mutations in minority populations.
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: Ruixia Guo, Haifeng Qiu, Qian Wang, Ke Su, Lei Chang, Mingbo Cai, Meng Mao, Aiping Bian
Journal: Journal of Clinical Oncology (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 .
Pelvic ultrasound-based deep learning models for accurate diagnosis of ovarian cancer: Retrospective multicenter study.
Authors: Hyun-Woong Cho, Sanghoon Lee, Jin Hwa Hong, Seonkyung Kim, Jaeyun Song, Jae Kwan Lee
Journal: Journal of Clinical Oncology (2024)

5543 Background: Although pelvic ultrasound is useful modality to diagnose ovarian cancer, there is few studies to evaluate the performance of deep learning model. Development of deep learning based on aggregating ultrasound images and clinical information such as age and CA-125 data might be beneficial to differentiated malignancy from benign ovarian cyst. The objective of this study is to build a deep learning model with advanced accuracy of differential diagnosis between malignant and benign lesions of ovary. Methods: Pelvic ultrasound images, information of age and ca-125 level at diagnosis from patients diagnosed with ovarian cancer or benign cyst during 2015-2022 were retrieved. The images were segmented into cystic and solid component and processed data for feature extraction. For convolutional neural network model development, patients were assigned to training dataset (565 patients), validation dataset (76 patients), and test dataset (163 patients). After feature extraction using this convolutional neural network, we also used age and tumor marker to classify these images as either malignant or benign. Using these datasets, we assessed the diagnostic value of the deep learning model. A new AI model to utilize image feature and clinical information together was developed. This model separates feature extractor and classifier from the architecture of conventional AI models, and the classifier receives clinical information data in addition to image information. ResNet50 and DenseNet121 were used in the conventional AI model. Results: In total, 804 patients who had ovarian tumors were included; 446 benign and 358 malignant. When pelvic ultrasound image of ovary was only used, ResNet50 showed AUC of 0.84 and DenseNet121 had AUC of 0.82 for this model to detect ovarian cancer. However, when segmented solid portion image and clinical data was combined with the ovary image, ResNet50 showed AUC of 0.95 and DenseNet121 had AUC of 0.96 for this model to detect ovarian cancer. Using the test data set, ResNet50 and DenseNet121 had sensitivities of 90% and 81%, specificity of 93% and 97%, positive predictive value of 92% and 95%, and negative predictive value of 92% and 86% to detect ovarian cancer, respectively. Conclusions: Binary classification model based on deep learning algorithms using pelvic ultrasound images can distinguish between benign and malignant ovarian tumors accurately. Segmentation of solid portion and clinical information of age and CA-125 at diagnosis combined with the pelvic ultrasound images increased the accuracy of the classification model.
Phase II study of pembrolizumab and lenvatinib in platinum sensitive recurrent ovarian cancer.
Authors: Smadar Bauer, Akram Saad, Inbal Greenhouse, Anna Ruth Rapoport, Shir Shahar, Tania Barnatan, Ronit Satchi-Fainaro, Ronnie Shapira-Frommer
Journal: Journal of Clinical Oncology (2024)

5581 Background: Ovarian cancer (OC) is characterized by a high recurrence rate following primary surgical and systemic therapy with decreasing efficacy of subsequent treatment lines and accumulating toxicity. Immunotherapy had shown limited efficacy in recurrent OC with 8% response rate in a notable cohort study (Keynote 100).The combination of Pembrolizumab (P) with Lenvatinib (L) was evaluated in a small cohort of platinum resistant OC (LEEP 005) with a 32% response rate. This study assessed the P+L combination’s effectiveness in the platinum sensitive recurrence setting. Methods: In this investigator initiated phase 2 study (NCT04519151), we enrolled patients with platinum sensitive recurrent OC. Inclusion criteria were high grade serous or endometrioid histology, maximum of two previous treatment lines, measurable disease per RECIST 1.1, reserved organ function, and ECOG of 0 or 1. Patients received P (200mg every three weeks) and L (20mg daily) until disease progression or unacceptable toxicity or up to 35 cycles of P. L treatment could be maintained beyond 35 courses of P per investigator decision. Study's primary end point is response rate (RR), and secondary end points encompass progression-free survival (PFS), overall survival (OS), duration of response (DOR), safety, and quality of life. Correlative study explored archival/fresh tumor tissue and blood biomarkers for response as well as fecal and vaginal microbiome. Results: Between May 2021 and July 2023 24 patients were treated. Median age was 65 years (range 43-77). 11(46%) received 1 prior treatment line and 11(46%) received prior bevacizumab. At a median follow up of 30 months, 12/24 (50%) had RECIST 1.1 response, 2 (8%) with CR and 10 (42%) with PR. Median PFS was 8 months. Median OS and DOR were not reached. At 6 and 12 months, response persisted in 10 and 3 patients, respectively. Treatment-related adverse events were noted in all patients, predominantly hypertension and fatigue. Dose reduction of L occurred in 19 (79%) patients mainly due to hypertension 8(33%), fatigue in 7(30%) and arthralgia in 5(21%). Discontinuation due to adverse event occurred in three patients (hepatitis, nephrotic range proteinuria, diabetic keto-acidosis). There was no treatment-related death. Data on the QOL analysis and biomarker study will be presented later. Conclusions: L+P combination showed meaningful responses and manageable toxicity in platinum sensitive recurrent OC patients thus potentially provides a non chemotherapy alternative. Effect on survival and response to subsequent therapies is yet to be evaluated. Further research is essential to pinpoint the patient subset that can benefit the most from this combination. Clinical trial information: NCT04519151 .
Use of cell-free DNA from ascites to identify variants and tumour evolution in a cohort of patients with advanced ovarian cancer.
Authors: Bonnita Werner, Elyse Powell, Jennifer Duggan, Marilisa Cortesi, Yeh Chen Lee, Vivek Arora, Ramanand Athavale, Michael Dean, Kristina Warton, Caroline Ford
Journal: Journal of Clinical Oncology (2024)

5547 Background: Accurate and clinically relevant molecular profiling is critical in the evolving landscape of precision treatments for ovarian cancer. Malignant ascites, a common manifestation in advanced ovarian cancer, provides easy access to tumour material in the form of cell-free DNA (cfDNA). Ascites fluid is an ideal liquid biopsy to enable molecular profiling and application of precision medicine as an alternative to tissue biopsy. Objectives: We aimed to identify clinically relevant variants in ascites and to examine tumour evolution by comparing matched samples from different points in the disease trajectory. Methods: A unique cohort of sequential ascites-derived cfDNA samples (26 samples from 15 participants, interval range 13-559 days), from people with ovarian cancer (clear cell and high-grade serous, aged 36-82) was collected. These were sequenced with the Illumina TSO-500 assay, along with matched DNA from ascites-derived tumour cells (n=5) and archived FFPE-tissue from surgery (n=5). cfDNA from one patient was additionally analysed with PCR-free sequencing, using an Oxford Nanopore Technology R9.4.1 MinION. Results: cfDNA had similar tumour purity, variant detection and reference alignment as well as improved coverage when compared to FFPE and ascites cell DNA. Somatic ovarian cancer-associated driver mutations were detected in 100% of cfDNA samples at mutation fractions of up to 0.9 MAF. 3 confirmed cases with somatic BRCA1/BRCA2 mutations were identifiable in ascites cfDNA, of these, ascites preceded surgery by 100 days or more in 2 cases, enabling earlier access to tumour tissue and expediting PARP-inhibitor access. Combined analysis of large-scale genomic alterations, loss of heterozygosity and tumour mutation burden identified 6 cases of high genomic instability (including 4 with mutations in BRCA1 and BRCA2). Over sequential ascites samples, changes in copy number profiles were observed and prevalence of subclones shifted by &gt;10% in 6 of 10 participants. Additionally, in one participant, selective deletion of Chr17p13.1 and a chromothripsis-affected Chr8q emerged between interval debulking surgery and disease recurrence, resulting in changes to clinically relevant TP53 and MYC variants over time. No artefactual single-base substitution signatures were observed in cfDNA, though results from 2 of 5 FFPE samples were &gt;20% sequencing artefact. Conclusions: Our work demonstrated the reliability of using cfDNA from ascites for molecular profiling, allowing a liquid biopsy of ovarian cancer when tumour tissue access may be restricted. This approach improves accessibility of tumour material, allowing capture of clinically actionable mutations prior to surgery or upon recurrence, following tumour evolution.