Publications by authors named "Jonathan A Ledermann"

Background: Ethnic and socioeconomic disparities in cancer outcomes are exacerbated by clinical trial underrepresentation. This study aims to identify inequalities in ethnicity and socioeconomic features among ovarian cancer clinical trial participants in two London cancer centres.

Methods: All ovarian cancer patients treated between 2017 and 2022 were included.

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  • The study aims to assess the baseline symptom burden experienced by patients with recurrent ovarian cancer and its relationship with progression-free survival and overall survival.
  • Analysis involved 948 patients with either platinum-resistant or potentially platinum-sensitive recurrent ovarian cancer receiving advanced chemotherapy, revealing that a significant majority experienced mild to severe symptoms, including pain, fatigue, and anxiety.
  • Results showed that higher symptom burden was linked to reduced progression-free survival and overall survival, highlighting the need for effective symptom management in clinical settings and trials.
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Purpose: Cancer antigen-125 (CA-125) is recommended by treatment guidelines and widely used to diagnose ovarian cancer recurrence. The value of CA-125 as a surrogate for disease progression (PD) and its concordance with radiologic progression are unclear, particularly for women with platinum-sensitive relapsed ovarian cancer (PSROC) who have responded to chemotherapy and treated with maintenance poly(ADP-ribose) polymerase inhibitor (PARPi).

Methods: In this pooled analysis of four randomized trials of maintenance PARPi or placebo (Study 19, SOLO2, ARIEL3, and NOVA), we extracted data on CA-125 PD as defined by Gynecologic Cancer InterGroup criteria and RECIST v1.

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Purpose: To evaluate the addition of ofranergene obadenovec (ofra-vec, VB-111), a novel gene-based anticancer targeted therapy, to once a week paclitaxel in patients with recurrent platinum-resistant ovarian cancer (PROC).

Methods: This placebo-controlled, double-blind, phase III trial (ClinicalTrials.gov identifier: NCT03398655) randomly assigned patients with PROC 1:1 to receive intravenous ofra-vec every 8 weeks with once a week IV paclitaxel or placebo with paclitaxel until disease progression.

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Objective: This prespecified exploratory analysis evaluated the association of gene expression signatures, tumor mutational burden (TMB), and multiplex immunohistochemistry (mIHC) tumor microenvironment-associated cell phenotypes with clinical outcomes of pembrolizumab in advanced recurrent ovarian cancer (ROC) from the phase II KEYNOTE-100 study.

Methods: Pembrolizumab-treated patients with evaluable RNA-sequencing (n = 317), whole exome sequencing (n = 293), or select mIHC (n = 125) data were evaluated. The association between outcomes (objective response rate [ORR], progression-free survival [PFS], and overall survival [OS]) and gene expression signatures (T-cell-inflamed gene expression profile [TcellGEP] and 10 non-TcellGEP signatures), TMB, and prespecified mIHC cell phenotype densities as continuous variables was evaluated using logistic (ORR) and Cox proportional hazards regression (PFS; OS).

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Background: Efficient biomarker discovery and clinical translation depend on the fast and accurate analytical output from crucial technologies such as multiplex imaging. However, reliable cell classification often requires extensive annotations. Label-efficient strategies are urgently needed to reveal diverse cell distribution and spatial interactions in large-scale multiplex datasets.

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Unlabelled: In the phase III JAVELIN Ovarian 200 trial, 566 patients with platinum-resistant/refractory ovarian cancer were randomized 1:1:1 to receive avelumab alone, avelumab plus pegylated liposomal doxorubicin (PLD), or PLD alone. Cardiac monitoring was included for all patients. We report left ventricular ejection fraction (LVEF) data from the trial.

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Purpose: To compare NFOSI-18 Disease Related Symptoms - Physical (DRSP), Total score, and side effect bother between maintenance rucaparib (600 mg twice daily) vs. placebo in the phase III ARIEL3 trial.

Methods: ARIEL3 (NCT01968213) included patients with ovarian carcinoma who responded to second-line or later platinum-based chemotherapy.

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  • Olaparib plus bevacizumab maintenance therapy shows improved survival outcomes for women with newly diagnosed, advanced ovarian cancer that has homologous recombination deficiency.
  • The Myriad myChoice diagnostic tested 2829 tumor samples, with 87% and 77% successfully undergoing mutation and Genomic Instability Score (GIS) testing, respectively.
  • The results reveal 16% of tumors had BRCA mutations and 37% had GIS rates ≥42, indicating the need for high-quality tumor samples to minimize testing failures, reflecting a successful implementation of testing across the NHS in the UK.
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The move toward consistent and comprehensive surgical pathology reports for cancer resection specimens has been a key development in supporting evidence-based patient management and consistent cancer staging. The International Collaboration on Cancer Reporting (ICCR) previously developed a data set for reporting of the ovarian, fallopian tube and primary peritoneal carcinomas which was published in 2015. In this paper, we provide an update on this data set, as a second edition, that reflects changes in the 2020 World Health Organization (WHO) Classification of Female Genital Tumours as well as some other minor modifications.

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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.

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Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have revolutionised the management of patients with high-grade serous and endometrioid ovarian cancer demonstrating significant improvements in progression-free survival. Whilst the greatest benefit is seen with mutant cancers, it is clear that the benefit extends beyond this group. This sensitivity is thought to be due to homologous recombination deficiency (HRD), which is present in up to 50% of the high-grade serous cancers.

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Definitions of platinum resistance have been questioned and changed over the last five years, even though no predictive biomarker of resistance exists. These have sculpted how we approach platinum retreatment and, consequently, how we devise new treatment strategies for those patients with tumour progression on platinum therapy. Platinum-non-eligible ovarian cancer is treated with single-agent non-platinum drugs.

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  • The Measure of Ovarian Symptoms and Treatment (MOST) is a validated tool designed to assess the benefits and side effects of palliative chemotherapy in women with recurrent ovarian cancer (ROC).
  • Researchers analyzed data from a cohort of 762 women to identify how different symptoms co-occurred and how they impacted health-related quality of life (HRQL).
  • Four main symptom clusters were found—abdominal, peripheral neuropathy, nausea and vomiting, and psychological symptoms—indicating that regular screening and management of these symptoms could improve HRQL for affected women.
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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.

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Objective: The Gynecologic Cancer InterGroup (GCIG)-Symptom Benefit Study was designed to evaluate the effects of chemotherapy on symptoms and health-related quality of life (HRQL) in women having chemotherapy for platinum resistant/refractory recurrent ovarian cancer (PRR-ROC) and potentially platinum sensitive with ≥3 lines of chemotherapy (PPS-ROC ≥3).

Methods: Participants completed the Measure of Ovarian Cancer Symptoms and Treatment (MOST) and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30 questionnaires at baseline and every 3-4 weeks until progression. Participants were classified symptomatic if they rated ≥4 of 10 in at least one-third of symptoms in the MOST index.

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Background: The absence of the putative DNA/RNA helicase Schlafen11 (SLFN11) is thought to cause resistance to DNA-damaging agents (DDAs) and PARP inhibitors.

Methods: We developed and validated a clinically applicable SLFN11 immunohistochemistry assay and retrospectively correlated SLFN11 tumour levels to patient outcome to the standard of care therapies and olaparib maintenance.

Results: High SLFN11 associated with improved prognosis to the first-line treatment with DDAs platinum-plus-etoposide in SCLC patients, but was not strongly linked to paclitaxel-platinum response in ovarian cancer patients.

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Importance: A total of 1% to 3% of patients treated with a poly(adenosine diphosphate-ribose) polymerase inhibitor for high-grade ovarian cancer (HGOC) develop therapy-related myeloid neoplasms (t-MNs), which are rare but often fatal conditions. Although the cause of these t-MNs is unknown, clonal hematopoiesis of indeterminate potential (CHIP) variants can increase the risk of primary myeloid malignant neoplasms and are more frequent among patients with solid tumors.

Objectives: To examine whether preexisting CHIP variants are associated with the development of t-MNs after rucaparib treatment and how these CHIP variants are affected by treatment.

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Cytoreductive surgery is the mainstay of treatment for high-grade epithelial ovarian cancer. Although for early stage disease outcomes following surgery alone are good, the risk of recurrence necessitates adjuvant chemotherapy for the majority of patients. Post-operative chemotherapy in advanced-stage disease, or neoadjuvant chemotherapy followed by surgery has improved progression-free survival (PFS) and overall survival (OS).

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