Publications by authors named "Lauriane Eberst"
Article Synopsis
- The GCIG Endometrial Cancer Consensus Conference was held in Incheon, South Korea, aimed at creating consensus statements to improve future clinical trials in endometrial cancer.
- Representatives from 33 member groups developed 18 statements across four key topics, focusing on treatment strategies and trial methodologies, including consideration for low-resource settings.
- For the first time, the conference included patient advocates and early-career investigators, resulting in a high consensus rate on the statements, reinforcing progress in global clinical research for endometrial cancer.
Article Synopsis
- - Ovarian cancer is a major cause of death among gynecological cancers, and platinum-based chemotherapy is the primary treatment method, along with maintenance strategies to extend chemotherapy intervals.
- - Current maintenance treatments include bevacizumab and poly ADP-ribose polymerase inhibitors, but these can only be used once during the disease's progression, leaving a gap in treatment for patients experiencing relapses.
- - A new international Phase II trial is exploring a combination of a therapeutic cancer vaccine (OSE2101) and anti-PD1 (pembrolizumab) as a maintenance therapy for patients with platinum-sensitive recurrences, regardless of prior treatments.
Article Synopsis
- * A survey conducted from February 2021 to August 2022 among healthcare professionals in France highlighted a lack of adherence to the 2018 ESGO recommendations for LACC treatment, with notable differences in practices between university hospitals and other settings.
- * Compliance rates were particularly low among gynecologic surgeons, with only 5.7% aligning with ESGO guidelines, which may directly affect patient outcomes; thus, there's a potential need for more structured care in specialized centers.
Purpose: Xevinapant is an orally available inhibitor of apoptosis proteins (IAP) inhibitor. Preclinical data suggest that IAP antagonism may synergize with immune checkpoint blockers by modulating the NFκB pathway in immune cells.
Patients And Methods: Adult patients with non-high microsatellite instability advanced/metastatic pancreatic ductal adenocarcinoma (PDAC) or colorectal cancer were enrolled in this phase Ib/II study and received pembrolizumab 200 mg every 3 weeks intravenously, and ascending doses of oral xevinapant (100, 150, and 200 mg daily for 14 days on/7 days off).
Tumor-associated macrophages (TAMs) are a critical determinant of resistance to PD-1/PD-L1 blockade. This phase 1 study (MEDIPLEX, NCT02777710) investigated the safety and efficacy of pexidartinib, a CSF-1R-directed tyrosine kinase inhibitor (TKI), and durvalumab (anti-PD-L1) in patients with advanced colorectal and pancreatic carcinoma with the aim to enhance responses to PD-L1 blockade by eliminating CSF-1-dependent suppressive TAM. Forty-seven patients were enrolled.
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- In October 2020, dostarlimab, a programmed death-1 inhibitor, was granted early access in France for treating advanced endometrial cancer based on the GARNET trial results and later approved by the European Medicines Agency in April 2021.
- A real-world analysis from November 2020 to June 2021 included data from 87 eligible patients who received at least one dose of dostarlimab, showcasing a disease control rate of 56% and an overall response rate of 35%, aligning with clinical trial findings.
- The study emphasized the urgent need for new treatment options for patients post-platinum in France and noted ongoing research into the efficacy and safety of dostarlim
Article Synopsis
- A significant portion (13%) of HER2-positive metastatic breast cancer patients treated with trastuzumab and pertuzumab experienced isolated Central Nervous System (CNS) progression, typically around 12 months after diagnosis.
- Among the 120 patients analyzed, nearly two-thirds received CNS-targeted local therapy, and results showed no difference in progression-free survival between those who continued trastuzumab-pertuzumab and those who switched to another treatment.
- Continuing trastuzumab-pertuzumab therapy after local treatment was linked to improved overall survival, indicating that more research and clinical trials are needed for effective treatment strategies in these cases.
Article Synopsis
- The study analyzes the error introduced when using the Kaplan-Meier estimate for survival data that is not fully mature, focusing on how different maturity levels affect long-term life expectancy projections in economic evaluations.
- It compared data from phase 3 trials reporting overall survival (OS) with 70% maturity to artificially truncated data sets representing lower maturities (30% and 50%) using various statistical methods.
- Results indicated that as OS maturity increases, the accuracy of life expectancy estimates improves, emphasizing the importance of using mature data when developing economic models.
Alterations in Homologous Recombination-Related Genes and Distinct Platinum Response in Metastatic Triple-Negative Breast Cancers: A Subgroup Analysis of the ProfiLER-01 Trial.
Elise Bonnet Véronique Haddad Stanislas Quesada Kim-Arthur Baffert Audrey Lardy-Cléaud Lauriane Eberst
J Pers Med
September 2022
Article Synopsis
- A specific type of metastatic triple-negative breast cancer (mTNBC) shows increased sensitivity to platinum-based chemotherapy due to homologous recombination deficiency (HRD), prompting a study to explore genetic alterations and their impact on treatment response.
- In a study involving mTNBC patients, tumors were analyzed for mutations in 19 HRR genes, and patients were grouped based on their molecular status to evaluate responses to platinum therapy.
- Results indicated that mutations in specific HRR genes and promoter methylation were linked to better disease control, suggesting that broader genetic evaluations could help identify more patients who might benefit from platinum treatment.
Article Synopsis
- The study compares laparoscopic interval debulking surgery (IDS) and laparotomy outcomes in patients with stage III or IV serous ovarian cancer post-neoadjuvant chemotherapy.
- Results showed no significant difference in overall survival (OS) and progression-free survival (PFS) between both surgical methods, although laparoscopy had fewer early postoperative complications and shorter hospital stays.
- Laparoscopy is suggested as a safe alternative to laparotomy for selected patients with advanced ovarian cancer, achieving comparable survival outcomes with reduced morbidity.
Epithelial ovarian cancer (EOC) is the most lethal of all gynecological cancers. Despite excellent responses to standard treatment in approximately 70% of patients, most of them will relapse within 5 years of initial treatment and many of them will develop chemotherapy-resistant disease. It is then important to find other means of treatment for these patients such as immunotherapy or targeted therapy.
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- Chemotherapy and standard treatments like anti-HER2 and PD-1 antibodies show limited long-term effectiveness for patients with gastroesophageal cancers.
- A study on 147 patients revealed that adenocarcinoma was the most common type, with significant genomic alterations found, including in genes like TP53 and ERBB2.
- Genomic profiling can identify treatable alterations in many patients, suggesting that using matched therapies could enhance survival rates, particularly in those with stage IV disease.
Article Synopsis
- * Despite being linked to poorer outcomes, new therapies have improved the long-term survival of HER2-positive breast cancer patients with BCBM.
- * Treatment strategies for BCBM now include surgery, stereotactic radiosurgery, and various medical therapies that can cross the compromised blood-brain barrier, showcasing a need for coordinated approaches in managing these complex cases.
Article Synopsis
- The study focused on analyzing the genetics and immune profiles of patients with advanced cancers to determine potential therapies, specifically in a pediatric group.
- It used advanced genomic testing methods on tumor samples from 50 young patients with high-risk cancers, identifying genetic mutations and possible targeted treatments.
- The findings showed that only a small percentage of pediatric patients could receive recommended targeted therapies, reflecting challenges similar to those faced in adult cancer treatment.
Article Synopsis
- A phase Ib study assessed the safety and effectiveness of combining emactuzumab and selicrelumab in patients with advanced solid tumors, particularly focusing on their pharmacokinetics and pharmacodynamics.
- The drugs were given via IV every three weeks, and while some dose-limiting toxicities were observed, the maximum tolerated doses weren't reached for either drug.
- Although the treatment resulted in a manageable safety profile and some pharmacodynamic activity, only 40.5% of patients achieved stable disease without significant objective clinical improvements.
Article Synopsis
- Advanced sarcoma is a challenging group of tumors with a poor outlook and limited treatment options, making them a potential target for molecular-based therapy (MBT).
- In a study involving 164 patients, genomic profiling identified relevant genetic alterations in 67% of cases, revealing a total of 289 alterations across many genes, with notable ones including TP53 and CDKN2A.
- Despite some MBT recommendations and a modest response in one case, the study concluded that while genomic profiling is feasible, it should not yet be a standard practice and requires more investigation through clinical trials.
Purpose Of Review: For patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, treatments that could prevent or delay occurrence of brain metastases would improve outcome.
Recent Findings: Few studies were specifically designed to assess brain metastasis prevention. Most evidence derives from subgroup analyses of randomized trials.
A Phase 1 dose-escalation study to evaluate safety, pharmacokinetics and pharmacodynamics of AsiDNA, a first-in-class DNA repair inhibitor, administered intravenously in patients with advanced solid tumours.
Christophe Le Tourneau Jean-Pierre Delord Nuria Kotecki Edith Borcoman Carlos Gomez-Roca Lauriane Eberst
Br J Cancer
November 2020
Article Synopsis
- AsiDNA is an innovative therapy that mimics double-stranded DNA breaks to trigger a response in tumor cells, engaging key enzymes that play a role in DNA repair.
- A Phase 1 study was conducted with 22 patients having advanced solid tumors to evaluate the drug's safety, tolerability, and pharmacokinetics, using various dose levels.
- The maximum tolerated dose was never reached, but the 600 mg dose was determined to be optimal for future studies, with a few cases of serious side effects reported at higher doses.
Article Synopsis
- The study explored survival factors in cancer patients suspected of having COVID-19, highlighting that these patients face a significantly high risk of death.
- Out of 302 cancer patients, 18.2% tested positive for SARS-CoV-2 via RT-PCR, with older patients and those with respiratory symptoms being more prevalent in this group.
- The death rates at a median follow-up of 25 days were 21% for RT-PCR-positive and 10% for RT-PCR-negative patients, with risk factors for death including male gender, poor performance status, and presence of respiratory symptoms, but the viral detection did not correlate with increased mortality.
Lessons Learned: The combination of the antivascular endothelial growth factor receptor 2 monoclonal antibody, ramucirumab, and the type II MET kinase inhibitor, merestinib, is tolerable. Preliminary efficacy data suggest that the combination may provide clinical benefit to patients with metastatic colorectal cancer (mCRC). Further development of this combination would likely necessitate the identification of subsets of patients with mCRC where the clinical benefit is of clinical relevance.
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- BRCA1 is a key tumor suppressor gene linked to familial breast cancer, particularly aggressive triple-negative types, and has roles in DNA repair and other crucial cellular processes.
- The study reveals that BRCA1 also functions as a translational regulator, influencing the production of specific proteins that are important for cancer biology.
- Findings suggest that translational control by BRCA1 could be a new mechanism underlying its tumor-suppressive activity, with the potential to identify ADAT2 as a biomarker for treatment response in patients with BRCA1 deficiencies.
Article Synopsis
- The text discusses various rare malignant ovarian tumors, including germ cell tumors, sex cords stromal tumors, and certain types of epithelial tumors, which collectively account for about 10% of all ovarian tumors.
- Due to their low prevalence and variety, there is limited data and treatment guidance for these tumors, and treatment approaches can differ significantly between tumor types.
- The article aims to provide a detailed overview of the pathology, clinical presentation, and therapy recommendations for selected rare ovarian tumors, referencing the latest national guidelines and key publications.
The transmission of an intact and stable genetic code at each cell division relies on different DNA repair systems. Germline mutations of some of these genes cause cancer predisposition, whereas somatic mutations are frequently found in various cancer types, generating genomic instability. As a consequence, cancer cell becomes more susceptible to additional DNA damage.
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