Feasibility of Manufacturing and Antitumor Activity of TIL for Advanced Endometrial Cancers.

Lifileucel, a tumor-infiltrating lymphocyte (TIL) cell therapy approved for advanced melanoma, demonstrates promise for treating other solid tumors, including endometrial cancer (EC). The current study evaluates the feasibility of manufacturing TILs from EC tumors using Iovance's proprietary 22-day Gen2 manufacturing process. Key parameters, including TIL yield, viability, immune phenotype, T-cell receptor clonality, and cytotoxic activity, were assessed.

Oral mucositis associated with antibody-drug conjugates in gynecologic oncology: strategies for prevention and treatment.

Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic option for the treatment of gynecologic malignancies and have become a key component of treatment strategies for recurrent ovarian, endometrial, and cervical cancers. These agents offer targeted tumor cell specificity while delivering potent cytotoxic agents. Despite their selectivity, ADCs are associated with unique treatment-related adverse events.

The GOG Foundation and EVA/LACOG partnership: a collaborative strategic alliance for clinical trial execution.

The collaborative efforts between GOG and LACOG are aimed at advancing clinical oncology research through strategic global partnerships, particularly related to the conduct of clinical trials. Herein, we provide the framework of this relationship addressing key operational components including establishing a shared Publication Policy. In addition, this initiative seeks to standardize contributions, recognize authorship fairly, and ensure compliance with agreed protocols.

Safety and efficacy of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with pembrolizumab in patients with platinum-resistant ovarian cancer.

Objective: Evaluate the efficacy and safety of mirvetuximab soravtansine-gynx (MIRV) plus pembrolizumab in dose escalation and expansion cohorts of heavily pretreated patients with platinum-resistant ovarian cancer (PROC).

Methods: Participants with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer whose disease relapsed ≤6 months from last platinum-based treatment received MIRV (6 mg/kg adjusted ideal body weight) and pembrolizumab (200 mg) intravenously once every 3 weeks. Tumor FRα expression thresholds were ≥25 % (dose escalation cohort) and ≥50 % (dose expansion cohort) of cells with ≥2+ membrane staining intensity.

Expanding the workforce of clinical trial investigators committed to gynecologic cancer research: the GOG Foundation, Inc's Scholar Career Development Award and New Investigator Program.

Objective: Training and supporting early-career investigators are essential for developing a resilient and competent clinical research workforce in gynecologic oncology. To address persistent gaps in mentorship, protected time, funding, and leadership pathways, the Gynecologic Oncology Group Foundation, Inc (GOG-F) launched two-tiered development programs: the GOG-F New Investigator Program and the GOG-F Scholar Career Development Award. This 5-year evaluation reports academic, leadership, accrual, and funding outcomes.

Efficacy and Safety of Avutometinib ± Defactinib in Recurrent Low-Grade Serous Ovarian Cancer: Primary Analysis of ENGOT-OV60/GOG-3052/RAMP 201.

Purpose: This study evaluated the efficacy and safety of avutometinib (rapidly accelerated fibrosarcoma/mitogen-activated extracellular signal-regulated kinase [MEK] clamp) alone or in combination with defactinib (focal adhesion kinase inhibitor) in patients with recurrent low-grade serous ovarian cancer (LGSOC).

Methods: In this phase II, open-label study, patients with recurrent, measurable LGSOC after ≥1 line of platinum chemotherapy were stratified by tumor Kirsten rat sarcoma virus homolog () mutation status and randomly assigned to oral avutometinib 4.0 mg two times per week monotherapy or avutometinib 3.

Veliparib concomitant with first-line chemotherapy and as maintenance therapy in ovarian cancer: Final overall survival and disease-related symptoms results.

Introduction: In the VELIA trial, the addition of veliparib to standard first-line platinum-based chemotherapy and continued as maintenance resulted in significantly longer median progression-free survival (PFS) compared with carboplatin plus paclitaxel induction therapy alone (23.5 vs 17.3 months; p < 0.

State of the Art: Therapies Now and Around the Corner for Gynecologic Cancers.

Therapeutic advances across the gynecologic cancer continuum have resulted in improvements in patient care and outcomes over the past decade, yet challenges remain. In ovarian cancer, the evolution of poly (ADP-ribose) polymerase (PARP) inhibitor therapy has resulted in marked benefit for patients with BRCA-mutated cancers but has also unmasked the need for new therapies in patients whose cancers are proficient in homologous recombination and lack vulnerability to PARP inhibitors, as well as for those patients whose cancers progress on PARP inhibitors. In endometrial cancer, immune checkpoint inhibitors (ICIs) have improved outcomes for patients receiving first-line therapy for advanced or recurrent disease when combined with standard-of-care chemotherapy.

Correction: Health disparities in cervical cancer: Estimating geographic variations of disease burden and association with key socioeconomic and demographic factors in the US.

[This corrects the article DOI: 10.1371/journal.pone.

Long-Term Survival in Patients With Low-Risk Cervical Cancer After Simple, Modified, or Radical Hysterectomy.

Importance: Three-year pelvic recurrence rate in women with low-risk cervical carcinoma was not inferior following simple hysterectomy (SH) vs modified radical hysterectomy (MRH) or radical hysterectomy (RH) in the Simple Hysterectomy and Pelvic Node Assessment randomized clinical trial, but the survival analysis of the trial was underpowered.

Objective: To evaluate long-term survival in low-risk cervical carcinoma following SH vs MRH or RH.

Design, Setting, And Participants: This cohort study included women undergoing SH, MRH or RH in US Commission on Cancer-accredited facilities participating in the National Cancer Database who received a diagnosis between January 2010 and December 2017 of International Federation of Gynecology and Obstetrics 2009 stage IA2 or IB1 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix (≤2 cm) and clinically negative lymph nodes.

Impact of adding the immune checkpoint inhibitor atezolizumab to first-line chemotherapy on progression-free survival in poor-prognosis ovarian cancer: A retrospective analysis from the IMagyn050 trial.

Purpose: Adding the anti-PD-L1 antibody atezolizumab to frontline chemotherapy-bevacizumab regimen did not improve progression-free survival (PFS) in ovarian cancer (OC) patients in IMagyn050 trial. This post-hoc analysis assessed the efficacy of atezolizumab in a subgroup of patients with particularly poor prognosis, as defined by the GCIG meta-analysis-characterized by a poor chemosensitivity and a suboptimal surgical resection.

Methodology: This analysis included 1199 evaluable participants with ≥3 available CA-125 concentrations, as required for KELIM score.

The dynamic immune behavior of primary and metastatic ovarian carcinoma.

Patients with high-grade serous ovarian carcinoma (HGSC) are usually diagnosed with advanced-stage disease, and the tumors often have immunosuppressive characteristics. Together, these factors are important for disease progression, drug resistance, and mortality. In this study, we used a combination of single-cell sequencing and spatial transcriptomics to identify the molecular mechanisms that lead to immunosuppression in HGSC.

Comparing Durvalumab, Olaparib, and Cediranib Monotherapy, Combination Therapy, or Chemotherapy in Patients with Platinum-Resistant Ovarian Cancer with Prior Bevacizumab: The Phase II NRG-GY023 Trial.

Purpose: We assessed the efficacy of anti-PD-L1 durvalumab in combination with olaparib and cediranib (DOC), compared with the standard-of-care chemotherapy (SOC) in patients with platinum-resistant ovarian cancer (PROC), who had prior bevacizumab.

Patients And Methods: NRG-GY023 was the first randomized four-arm superiority phase II trial enrolling patients with high-grade serous/endometrioid or clear-cell PROC with prior bevacizumab exposure. Patients were randomized 1:2:2:2 to SOC (weekly paclitaxel, topotecan, or pegylated liposomal doxorubicin), DOC, durvalumab + cediranib (DC), or olaparib + cediranib (OC).

Patient-reported outcomes from the MIRASOL trial evaluating mirvetuximab soravtansine versus chemotherapy in patients with folate receptor α-positive, platinum-resistant ovarian cancer: a randomised, open-label, phase 3 trial.

Background: Mirvetuximab soravtansine-gynx (MIRV) is a first-in-class antibody-drug conjugate targeting folate receptor α (FRα), approved by the US Food and Drug Administration for the treatment of platinum-resistant ovarian cancer in the USA. Here, we report patient-reported outcomes for participants treated with MIRV compared with investigator's choice of chemotherapy from the phase 3 MIRASOL trial, which met its primary endpoint of progression-free survival and key secondary endpoints of objective response rate and overall survival.

Methods: The MIRASOL trial was a confirmatory, phase 3, randomised, controlled, open-label trial, building on the phase 2 SORAYA trial which had previously demonstrated the safety and efficacy of MIRV in platinum-resistant ovarian cancer.

A review of mirvetuximab soravtansine-gynx in folate receptor alpha-expressing platinum-resistant ovarian cancer.

Purpose: To evaluate the pharmacology, efficacy, safety, and dosing and administration considerations (including adjusted ideal body weight [AIBW] dosing) for mirvetuximab soravtansine-gynx, a first-in-class folate receptor alpha (FRα)-directed antibody-drug conjugate for platinum-resistant ovarian cancer (PROC).

Summary: A literature search was conducted in PubMed using the terms "ovarian cancer" and "mirvetuximab soravtansine" of articles published from inception to April 16, 2024. Relevant publications, abstracts, and clinical trials were reviewed.

Surrogate endpoints for overall survival in randomized clinical trials testing antibody-drug conjugates.

Background: The surrogacy of overall response rate (ORR) or progression-free survival (PFS) for overall survival (OS) at the trial-level in randomized clinical trials (RCTs) testing antibody-drugs conjugates (ADC) has never been investigated.

Methods: RCTs testing ADCs in patients with advanced solid tumors and reporting data on OS and PFS and/or ORR were analyzed. The main objective was to assess the trial-level association between the surrogate endpoints (ORR or PFS) and the reference endpoint (OS), overall and in subgroups of trials defined by tumor type, number of previous lines of systemic treatments, and specific ADC features.

Platinum-free interval and response to platinum retreatment or lenvatinib/pembrolizumab in patients with recurrent endometrial cancer: A real-world endometrial cancer molecularly targeted therapy consortium cohort study.

Objective: We sought to determine the association between platinum-free interval (PFI) and response to retreatment with platinum-based chemotherapy vs lenvatinib/pembrolizumab in patients with recurrent endometrial cancer.

Methods: Endometrial Cancer Molecularly Targeted Therapy (ECMT2) Consortium patients with recurrent disease were included in this retrospective analysis if they received first-line treatment with platinum-based chemotherapy (adjuvant or first recurrence), followed by second-line re-treatment with platinum or lenvatinib/pembrolizumab. PFI was defined as time between date of last platinum to start date of second-line therapy.

Melanoma-associated antigen A4: A cancer/testis antigen as a target for adoptive T-cell receptor T-cell therapy.

T-cell receptor (TCR) T-cell therapies are adoptive cell therapies in which patient cells are engineered to express TCRs targeting specific cancer antigens and infused back into the patient. Since TCR recognition depends on antigen presentation by the human leukocyte antigen system, TCRs can respond to intracellular antigens. Cancer/testis antigens (CTAs) are a large family of proteins, many of which are only expressed in cancerous tissue and immune-privileged germline sites.

Parent Perspectives on Youth Cannabis Use and Mental Health: Impacts, Challenges, and Recommendations.

Cannabis use among youth and young adults (YYA) is rising and poses serious mental health risks, especially with the availability of high-potency products. Parents are often the first to observe the potential impacts of cannabis use and are essential in recognizing early warning signs, facilitating treatment, and supporting recovery. However, limited research has examined the perspectives of parents whose children experience severe mental health challenges following cannabis use.

Nivolumab With or Without Ipilimumab in Patients With Recurrent or Metastatic Merkel Cell Carcinoma: A Nonrandomized, Open-Label, International, Multicenter Phase I/II Study.

Purpose: Approximately 50% of patients with advanced Merkel cell carcinoma (MCC) have primary or acquired resistance to PD-(L)1 blockade, which may be overcome using combination immune checkpoint inhibition (ICI) with anti-cytotoxic T lymphocyte antigen-4 antibody. We present results from the recurrent/metastatic MCC cohort in CheckMate 358, a nonrandomized, multicohort, phase I/II study of nivolumab (NIVO) with or without ipilimumab (IPI) in virus-associated cancers (ClinicalTrials.gov identifier: NCT02488759).

Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: ASCO Guideline Update.

Purpose: To provide updated guidance regarding neoadjuvant chemotherapy (NACT) and primary cytoreductive surgery (PCS) among patients with stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer (epithelial ovarian cancer [EOC]).

Methods: A multidisciplinary Expert Panel convened and updated the systematic review.

Results: Sixty-one studies form the evidence base.

A pan-tumor review of the role of poly(adenosine diphosphate ribose) polymerase inhibitors.

Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors, such as olaparib, talazoparib, rucaparib, and niraparib, comprise a therapeutic class that targets PARP proteins involved in DNA repair. Cancer cells with homologous recombination repair defects, particularly BRCA alterations, display enhanced sensitivity to these agents because of synthetic lethality induced by PARP inhibitors. These agents have significantly improved survival outcomes across various malignancies, initially gaining regulatory approval in ovarian cancer and subsequently in breast, pancreatic, and prostate cancers in different indications.