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.

Rucaparib for maintenance treatment of platinum-sensitive, recurrent ovarian carcinoma: Final results of the phase 3, randomized, placebo-controlled ARIEL3 trial.

Background: In ARIEL3, rucaparib maintenance significantly improved progression-free survival (PFS; primary endpoint) and long-term follow-up (LTFU) outcomes (including PFS2: time to disease progression on subsequent therapy or death) versus placebo in patients with recurrent, platinum-sensitive ovarian cancer. Here we report the final analysis of overall survival (OS; key secondary endpoint), LTFU outcomes, and safety.

Methods: OS and updated LTFU efficacy outcomes were analyzed (data cutoff date: April 4, 2022) across three nested populations (BRCA-mutated, homologous recombination deficient [HRD], and intention to treat [ITT]).

Relacorilant and nab-paclitaxel in patients with platinum-resistant ovarian cancer (ROSELLA): an open-label, randomised, controlled, phase 3 trial.

Background: Relacorilant, a first-in-class selective glucocorticoid receptor antagonist, increases a tumour's sensitivity to chemotherapy by reducing cortisol signalling. This study aimed to show whether the addition of relacorilant to nab-paclitaxel improves progression-free and overall survival in females with platinum-resistant ovarian cancer.

Methods: This randomised, controlled, open-label phase 3 trial (ROSELLA [GOG-3073/ENGOT-ov72]) was done at 117 hospitals and community oncology treatment centres in 14 countries across Australia, Europe, Latin America, North America, and South Korea.

Overall survival with maintenance olaparib in platinum-sensitive relapsed ovarian cancer by somatic or germline BRCA and homologous recombination repair mutation status.

Background: The open-label, single-arm, multicentre ORZORA trial (NCT02476968) evaluated maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSR OC) with a germline (g) or somatic (s) BRCA1 and/or BRCA2 mutation (BRCAm) or a non-BRCA homologous recombination repair mutation (non-BRCA HRRm).

Methods: Patients were in response to platinum-based chemotherapy after ≥2 prior lines of treatment and underwent prospective central screening for tumour BRCA status, then central gBRCAm testing to determine sBRCAm or gBRCAm status. An exploratory cohort evaluated non-BRCA HRRm in 13 predefined genes.

Pembrolizumab in Patients With Advanced Clear Cell Gynecological Cancer: A Phase 2 Nonrandomized Clinical Trial.

Importance: Advanced clear cell gynecological cancers (CCGCs) have a poor prognosis, with response rates to second-line chemotherapy less than 8%. Preliminary clinical activity with programmed cell death 1 protein (PD-1) inhibitors reported in CCGC merits further investigation.

Objective: To assess the clinical benefit of pembrolizumab in patients with previously treated advanced CCGC.

Germline BRCA1/2 status and chemotherapy response score in high-grade serous ovarian cancer.

Background: High-grade serous ovarian cancer (HGSOC) can be treated with platinum-based neoadjuvant chemotherapy (NACT) and delayed primary surgery (DPS). Histopathological response to NACT can be assessed using Böhm's chemotherapy response score (CRS). We investigated whether germline BRCA1/2 (gBRCA1/2) genotype associated with omental CRS phenotype.

The VALTIVE1 study protocol: a study for the validation of Tie2 as the first tumour vascular response biomarker for VEGF inhibitors.

Background: Anti-angiogenic, VEGF inhibitors (VEGFi) increase progression-free survival (PFS) and, in some cases, overall survival in many solid tumours. However, their use has been compromised by a lack of informative biomarkers. We have shown that plasma Tie2 is the first tumour vascular response biomarker for VEGFi in ovarian, colorectal and gall bladder cancer: If plasma Tie2 concentrations do not change after 9 weeks of treatment with a VEGFi, the patient does not benefit, whereas a confirmed reduction of at least 10% plasma Tie2 defines a vascular response with a hazard ratio (HR) for PFS of 0.

Extended panel testing in ovarian cancer reveals BRIP1 as the third most important predisposition gene.

Purpose: The prevalence of germline pathogenic variants (PVs) in homologous recombination repair (HRR) and Lynch syndrome (LS) genes in ovarian cancer (OC) is uncertain.

Methods: An observational study reporting the detection rate of germline PVs in HRR and LS genes in all OC cases tested in the North West Genomic Laboratory Hub between September 1996 and May 2024. Effect sizes are reported using odds ratios (ORs) and 95% confidence intervals (95% CI) for unselected cases tested between April 2021 and May 2024 versus 50,703 controls from the Breast Cancer Risk after Diagnostic Gene Sequencing study.

Once daily cediranib and weekly paclitaxel to prevent malignant bowel obstruction in at-risk patients with platinum-resistant ovarian cancer (CEBOC): a single-arm, phase II safety trial.

Objective: Cytotoxic chemotherapy for ovarian cancer can be augmented by co-administration of vascular endothelial growth factor inhibitors but these are contraindicated in patients with bowel obstruction due to the risk of gastrointestinal perforation. We evaluated the safety and feasibility of paclitaxel plus cediranib to treat patients with platinum-resistant ovarian cancer at risk of malignant bowel obstruction.

Methods: A phase II trial included eligible patients between March 2018 and February 2021, identified by clinical symptoms and radiographic risk factors for malignant bowel obstruction.

Real-World Concordance between Germline and Tumour Status in Epithelial Ovarian Cancer.

Patients diagnosed with epithelial ovarian cancer may undergo reflex tumour / testing followed by germline testing in patients with a positive tumour test result. This testing model relies on tumour / tests being able to detect all types of pathogenic variant. We analysed germline and tumour test results from patients treated for epithelial ovarian cancer at our specialist oncological referral centre.

Molecular Results and Potential Biomarkers Identified from the Phase 3 MILO/ENGOT-ov11 Study of Binimetinib versus Physician Choice of Chemotherapy in Recurrent Low-Grade Serous Ovarian Cancer.

Purpose: We present the results of a post hoc tumor tissue analysis from the phase 3 MILO/ENGOT-ov11 study (NCT01849874).

Patients And Methods: Mutation/copy-number analysis was performed on tissue obtained pre-randomization. The Kaplan-Meier method was used to estimate progression-free survival (PFS).

Efficacy and Safety of Weekly Paclitaxel Plus Vistusertib vs Paclitaxel Alone in Patients With Platinum-Resistant Ovarian High-Grade Serous Carcinoma: The OCTOPUS Multicenter, Phase 2, Randomized Clinical Trial.

Importance: Patients with platinum-resistant or refractory ovarian high-grade serous carcinoma (PR-HGSC) have a poor prognosis and few therapeutic options. Preclinical studies support targeting PI3K/AKT/mTOR signaling in this setting, and a phase 1 study of the dual mTORC1/mTORC2 inhibitor vistusertib with weekly paclitaxel showed activity.

Objective: To evaluate whether the addition of vistusertib to weekly paclitaxel improves clinical outcomes in patients with PR-HGSC.

Multi-Maintenance Olaparib Therapy in Relapsed, Germline BRCA1/2-Mutant High-Grade Serous Ovarian Cancer (MOLTO): A Phase II Trial.

Purpose: A single maintenance course of a PARP inhibitor (PARPi) improves progression-free survival (PFS) in germline BRCA1/2-mutant high-grade serous ovarian cancer (gBRCAm-HGSOC). The feasibility of a second maintenance course of PARPi was unknown.

Patients And Methods: Phase II trial with two entry points (EP1, EP2).

Is Reflex Germline Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older?

Women diagnosed with non-mucinous high-grade epithelial ovarian cancer (EOC) in England are often reflex-tested for germline and tumour / variants. The value of germline testing in women diagnosed aged ≥80 is questionable. We performed an observational study of all women diagnosed with non-mucinous high-grade EOC who underwent germline and tumour testing by the North West of England Genomic Laboratory Hub.

Patients, family members and healthcare professionals' top ten research priorities for adults receiving home parenteral nutrition for malignant or benign disease.

Background & Aims: Home parenteral nutrition (HPN) is the primary treatment for chronic intestinal failure (CIF) due to non-malignant disease and is increasingly used in patients with a diagnosis of cancer. This project engaged with patients, family members and healthcare professionals to ascertain what questions they want researched.

Methods: This study followed the five-stage process of the James Lind Alliance that involved (1) setting up a steering group, (2) carrying out an initial survey to gather participants' questions, (3) data processing, (4) an interim priority setting survey and (5) final priority setting workshop.

Clinical and molecular characteristics of ARIEL3 patients who derived exceptional benefit from rucaparib maintenance treatment for high-grade ovarian carcinoma.

Objective: ARIEL3 (NCT01968213) is a placebo-controlled randomized trial of the poly(ADP-ribose) polymerase inhibitor rucaparib as maintenance treatment in patients with recurrent high-grade ovarian carcinoma who responded to their latest line of platinum therapy. Rucaparib improved progression-free survival across all predefined subgroups. Here, we present an exploratory analysis of clinical and molecular characteristics associated with exceptional benefit from rucaparib.

Home Parenteral Nutrition in Patients with Advanced Cancer: Quality Outcomes from a Centralized Model of Care Delivery.

Lack of expertise in home parenteral nutrition (HPN) management has been reported as a barrier to its initiation in patients with advanced cancer (AC), and there are limited data describing hospital readmissions and HPN-related complications. We aimed to assess a centralized approach for managing HPN in AC and evaluate associated outcomes, including hospital readmissions and HPN-related complications. This was a cohort study of adults with AC requiring palliative HPN between 2010-2018 at a tertiary intestinal failure (IF) center, primarily utilizing a centralized model of HPN oversight to discharge patients remotely from an oncology center to their homes over a wide geographic area.

Predicting the likelihood of a pathogenic variant being somatic by testing only tumour DNA in non-mucinous high-grade epithelial ovarian cancer.

Aims: Clinical guidelines recommend testing both germline and tumour DNA for pathogenic variants (PVs) in non-mucinous high-grade epithelial ovarian cancer (NMEOC). In this study, we show that some tumour PVs are highly likely to be somatic based on certain clinical and variant characteristics, meaning it may not be necessary to test all NMEOC cases for germline PVs.

Methods: An observational study that included all tumour PVs detected in cases of NMEOC in the Northwest of England between July 2017 and February 2022.

Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal cancer treatment (ICON8): overall survival results from an open-label, randomised, controlled, phase 3 trial.

Background: Standard-of-care first-line chemotherapy for epithelial ovarian cancer is carboplatin and paclitaxel administered once every 3 weeks. The JGOG 3016 trial reported significant improvement in progression-free and overall survival with dose-dense weekly paclitaxel and 3-weekly (ie, once every 3 weeks) carboplatin. However, this benefit was not observed in the previously reported progression-free survival results of ICON8.