Mirvetuximab soravtansine in folate receptor alpha (FRα)–high platinum-resistant ovarian cancer: final overall survival and post hoc sequence of therapy subgroup results from the SORAYA trial

International Journal of Gynecological Cancer, Journal Year: 2024, Volume and Issue: 34(8), P. 1119 - 1125

Published: June 10, 2024

Objective The single-arm, phase II SORAYA trial ( NCT04296890 ) of mirvetuximab soravtansine-gynx in folate receptor alpha (FRα)–high platinum-resistant ovarian cancer (n=105 (efficacy-evaluable)) met its primary endpoint with an objective response rate 32.4% (95% CI, 23.6 to 42.2). Here we report final results for overall survival and post hoc rates subgroups by sequence number prior therapies. Methods Eligible patients had high-grade serous high FRα expression one three therapies (prior bevacizumab required). Enrolled participants received 6 mg/kg adjusted ideal body weight intravenously once every 3 weeks until progressive disease, unacceptable toxicity, withdrawal consent, or death. Final were assessed efficacy-evaluable participants. safety population included all who ≥1 dose soravtansine-gynx. Results At data cut-off (December 22, 2022; n=105), median was 15.0 months 11.5 18.7). Median two therapy lines 18.7 13.8 not estimable (NE)) 11.6 7.1 16.7) lines. NE) poly (ADP-ribose) polymerase inhibitor (PARPi) treatment versus 14.0 those without. (data cut-off: November 17, 2021) differed among as their first the setting (34.8%; 95% 23.5 47.6) a different (28.2%; 44.9) platinum-sensitive (34.0%; 24.6 44.5) (17.6%; 3.8 43.4). No new signals observed. Conclusion These support clinically meaningful efficacy FRα-expressing cancer, irrespective sequence.

Language: Английский

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Phase 1b study of intraperitoneal ipilimumab and nivolumab in patients with recurrent gynecologic malignancies with peritoneal carcinomatosis

Med, Journal Year: 2024, Volume and Issue: 5(4), P. 311 - 320.e3

Published: March 11, 2024

Language: Английский

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TGF β1 promotes the polarization of M2-type macrophages and activates PI3K/mTOR signaling pathway by inhibiting ISG20 to sensitize ovarian cancer to cisplatin

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 134, P. 112235 - 112235

Published: May 17, 2024

Language: Английский

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First evaluation of [68Ga]Ga-NOTA-(TMVP1)2 for imaging VEGFR-3 in ovarian cancer patients

American Journal of Nuclear Medicine and Molecular Imaging, Journal Year: 2025, Volume and Issue: 15(2), P. 65 - 73

Published: Jan. 1, 2025

Language: Английский

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Low-dose lenvatinib and anti-programmed cell death protein-1 combination therapy in patients with heavily pre-treated recurrent ovarian and endometrial cancer: a pilot study

International Journal of Gynecological Cancer, Journal Year: 2024, Volume and Issue: 34(8), P. 1203 - 1210

Published: April 24, 2024

Treatment options for heavily pre-treated recurrent ovarian and endometrial cancer are limited. Lenvatinib plus anti-programmed cell death protein-1 (PD-1) combination therapy has been efficacious in advanced cancer, but at the recommended dose level, high-grade adverse events occur lead to drug discontinuation. This study evaluated feasibility of low-dose lenvatinib anti-PD-1 patients with cancer. is a single-arm, protocol-based pilot study. Patients or who had least one line previous were included given 8 12 mg daily (based on patient's weight) therapy. The primary endpoint was objective response rate. Twenty-one enrolled, including 15 six All pre-treated, median number lines treatment cohorts three two, respectively. After follow-up 11.0 months (range 6.8-23.9), rate 46.7% (95% CI 21.3% 73.4%) 66.7% 22.3% 95.7%), duration 5.3 0 11.7) 6.1 2.4 9.8) months, progression-free survival 4.1 2.6 5.6) 6.6 1.7 11.5) No grade 4 5 occurred. Eight (38.1%) reduction. There no discontinuation alone, only patient discontinued both drugs due events. Low-dose showed promising efficacy favorable tolerability

Language: Английский

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Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer

Open Medicine, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 1, 2025

Primary chemoresistance to platinum-based treatment is observed in approximately 33% of individuals diagnosed with ovarian cancer; however, conventional clinical markers exhibit limited predictive value for chemoresistance. This study aimed discover new genetic that can predict primary resistance chemotherapy. Through the analysis three GEO datasets (GSE114206, GSE51373, and GSE63885) utilizing bioinformatics methodologies, we identified two specific genes, MFAP4 EFEMP1. The findings revealed areas under receiver operating characteristic curves EFEMP1 were 0.716 0.657 training cohort, 0.629 0.746 testing respectively. In all cases or treated platin, high expression was linked shortened overall survival progression-free survival. positively correlated epithelial-mesenchymal transition, TGF-β signaling, KRAS so on. groups exhibited elevated stromal, immune, ESTIMATE scores. Finally, constructed a regulatory network involving lncRNA-miRNA-mRNA interactions. summary, have potential serve as indicators both response chemotherapy rates, might be regarded innovative biomarkers therapeutic targets OC patients.

Language: Английский

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The Role of Cytoreductive Surgery in Platinum-Resistant Ovarian Cancer (PROC): A Systematic Review

Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 217 - 217

Published: Jan. 11, 2025

Platinum-resistant ovarian cancer (PROC) has limited therapeutic options, and the role of cytoreductive surgery (CRS) in improving survival outcomes remains uncertain. We performed a systematic review to evaluate oncological benefit CRS on PROC patients associated surgical morbidity mortality. followed prospective protocol according PRISMA guidelines. searched PubMed, Medline, Embase till October 2024. used "Population Intervention Comparator Outcomes (PICO)" framework. Our population included women with epithelial who underwent with/without chemotherapy. overall (OS), progression-free-survival (PFS), post-operative mortality Quality Life. search yielded 6590 citations; six studies (N = 155 patients) were included. There is evidence available PROC, notable variation reported outcomes' measures; therefore, we unable perform quantitative synthesis. demonstrated benefits well-selected patients, particularly those limited, isolated recurrences, low tumour burden, good performance status. Complete resection (R0) was significantly longer OS/PFS compared had suboptimal surgeries (R1/R2). seems extend carefully selected especially disease spread favourable profiles. Nevertheless, carries substantial risks, its appear contingent upon achieving R0. Further trials standardised patient selection criteria are needed define CRS's PROC. At present, should be considered within multidisciplinary approach specialised gynaecological oncology centres, careful assessment patient-specific risk factors potential for R0 resection.

Language: Английский

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High Frequency of PIK3R1 Alterations in Ovarian Cancers: Clinicopathological and Molecular Associations

Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 269 - 269

Published: Jan. 15, 2025

Background: The phosphoinositide 3-kinase (PI3K) pathway is activated in multiple cancers. However, the significance of PIK3R1 encoding PI3K regulatory subunit, an inhibitor catalytic subunit encoded by PIK3CA, ovarian cancer development largely unknown. Methods: Here, we investigated genomic alterations and gene expression direct sequencing qPCR methods 197 results were correlated with clinicopathological molecular variables patient outcomes. Results: In addition to mutations (3.5%) allelic losses (28.4%), observed a very high frequency decreased mRNA levels carcinomas (95.8%). Tumors mostly represented low-stage cancers endometrioid clear-cell type. deletion underexpression shared similar phenotypes high-grade (p = 0.003 p 0.025, respectively). Allelic loss was also associated advanced stages 0.003) serous histotypes 0.004). copy number 0.009). coexisted PTEN 0.041), whereas linked PIK3CA amplification 0.038 0.033, Low diminished probability complete response (OR 0.07, 0.03) patients treated platinum-based regimens. Conclusions: may contribute different malignant potential changes. aberrations suggests their importance deregulation, they potentially serve as alternative markers for therapy these inhibitors.

Language: Английский

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The value of MRI in differentiating ovarian clear cell carcinoma from other adnexal masses with O-RADS MRI scores of 4–5

Insights into Imaging, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 29, 2025

Abstract Objective To assess the utility of clinical and MRI features in distinguishing ovarian clear cell carcinoma (CCC) from adnexal masses with ovarian-adnexal reporting data system (O-RADS) scores 4–5. Methods This retrospective study included 850 patients indeterminate on ultrasound. Two radiologists evaluated all preoperative MRIs using O-RADS risk stratification system. Patients 4–5 were divided into a training set ( n = 135, hospital A) test 86, B). Clinical compared between CCC non-CCC patients. Analysis variance support vector machine used to develop four prediction models. Tenfold cross-validation was applied determine hyperparameters. Model performance by area under curve (AUC) decision curve. Results 221 (30 CCCs, 191 non-CCCs). CA125, HE4, CEA, ROMA, endometriosis, shape, parity, unilocular, component, growth pattern mural nodules, high signal T1WI, number ratio intensity, ADC value significantly different CCCs non-CCCs. The kappa interobserver correlation coefficient each feature exceeded 0.85. comprehensive model combining had greater AUC than tumour maker (0.92 vs 0.66 0.78 set; both p < 0.05), displaying improved net benefit. Conclusions can effectively differentiate Critical relevance statement has incidence rate Asians limited sensitivity platinum chemotherapy. improves ability applicability for facilitating individualised decision-making. Key Points Identifying preoperatively is beneficial treatment planning. Ovarian tends be high-signal big size, endometriosis low CEA. model, integrating features, Graphical

Language: Английский

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Emerging Therapeutic Targets for Platinum-Resistant Ovarian Cancer

Advances in Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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