Publications by authors named "Coraline Dubot"
Objective: To evaluate the prognostic impact of circulating tumor DNA (ctDNA) detection at diagnosis (T0) and its early decrease after one cycle (T1) of neoadjuvant chemotherapy (NACT) in patients with advanced epithelial ovarian cancer (EOC) included in the CHIVA trial (NCT01583322).
Methods: Blood samples were collected at T0 and before each administration of NACT. Circulating tumor DNA detection was performed by next-generation sequencing.
Background: Ovarian cancer (OC) remains one of the most challenging and deadly malignancies facing women today. While PARP inhibitors (PARPis) have transformed the treatment landscape for women with advanced OC, many patients will relapse and the PARPi-resistant setting is an area of unmet medical need. Traditional immunotherapies targeting PD-1/PD-L1 have failed to show any benefit in OC.
View Article and Find Full Text PDFArticle Synopsis
- The study examines the entire pathway of older adults’ participation in cancer clinical trials, identifying rates of non-invitation and refusal.
- It highlights sociocultural factors, such as social isolation and family dynamics, as major reasons for lower participation rates among older patients.
- The findings indicate that improving inclusion in clinical trials should focus on the interaction between healthcare professionals and patients, rather than solely on the patients themselves.
Importance: The KEYNOTE-826 randomized clinical trial showed statistically significant and clinically meaningful survival benefits with the addition of pembrolizumab to chemotherapy with or without bevacizumab in patients with persistent, recurrent, or metastatic cervical cancer. Treatment effects in patient subgroups of the study population are unknown.
Objective: To assess efficacy outcomes in patient subgroups of KEYNOTE-826.
Article Synopsis
- The KEYNOTE-826 trial tested the effectiveness of pembrolizumab combined with chemotherapy in patients with persistent, recurrent, or metastatic cervical cancer, showing significant improvements in survival rates compared to placebo plus chemotherapy.
- At the final data analysis, median overall survival (OS) for those receiving pembrolizumab was significantly higher than for those on placebo, with results of 28.6 months vs. 16.5 months in one group and similar patterns in others, indicating strong benefits across various patient populations.
- However, there were more grade ≥3 adverse events reported in the pembrolizumab group (82.4%) compared to the placebo group (75.4%), highlighting the need to consider potential side effects alongside treatment
Article Synopsis
- Recent advancements in treating advanced cervical cancer now include immunotherapy options like pembrolizumab for patients with PD-L1 positive tumors, as well as the availability of generic bevacizumab alongside traditional chemotherapy.
- Cemiplimab can also be prescribed for patients who relapse after platinum-based treatments and haven't received immunotherapy, regardless of PD-L1 status.
- A thorough pre-treatment evaluation using imaging and PD-L1 status is essential for determining treatment eligibility, and multidisciplinary discussions are encouraged for tailored locoregional care, while early supportive care and clinical trial participation are advised.
Concurrent chemoradiotherapy (CRT) with blockade of the PD-1 pathway may enhance immune-mediated tumor control through increased phagocytosis, cell death, and antigen presentation. The NiCOL phase 1 trial (NCT03298893) is designed to determine the safety/tolerance profile and the recommended phase-II dose of nivolumab with and following concurrent CRT in 16 women with locally advanced cervical cancer. Secondary endpoints include objective response rate (ORR), progression free survival (PFS), disease free survival, and immune correlates of response.
View Article and Find Full Text PDFBackground: In the KEYNOTE-826 study, the addition of the anti-PD-1 monoclonal antibody pembrolizumab to chemotherapy with or without bevacizumab improved overall survival and progression-free survival (primary endpoints) versus placebo plus chemotherapy with or without bevacizumab, with manageable toxicity, in patients with persistent, recurrent, or metastatic cervical cancer. In this Article, we report patient-reported outcomes (PROs) from KEYNOTE-826.
Methods: KEYNOTE-826 is a multicentre, randomised, phase 3 trial in 151 cancer treatment centres in 19 countries.
Article Synopsis
- The study investigates how the ability of ovarian cancer (OC) cells to form RAD51 foci after DNA damage can serve as a functional measure of homologous recombination deficiency (HRD) and its link to treatment response to platinum-based chemotherapy.
- Tumor samples from the CHIVA trial were analyzed, revealing that 54% of tumors were RAD51-low, which correlated with better responses to neoadjuvant platinum therapy and longer progression-free survival.
- Interestingly, within the BRCAmut tumors, those classified as RAD51-high demonstrated a poorer response to chemotherapy, challenging expectations about their treatment sensitivity.
Aim: The oral anti-angiogenic therapy nintedanib prolongs progression-free survival (PFS) when combined with chemotherapy after primary surgery for advanced epithelial ovarian cancer. The randomized phase II CHIVA trial evaluated the impact of combining nintedanib with neoadjuvant chemotherapy (NACT) for epithelial ovarian cancer.
Methods: Patients with newly diagnosed unresectable FIGO stage IIIC-IV epithelial ovarian cancer received 3-4 cycles of carboplatin plus paclitaxel every 3 weeks as NACT before interval debulking surgery (IDS), followed by 2-3 post-operative cycles.
Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial.
Lancet Oncol
November 2022
Article Synopsis
- The PADA-1 trial investigated the effectiveness of switching therapy in advanced breast cancer patients with rising ESR1 mutations, focusing on the combination of fulvestrant and palbociclib.
- It involved a randomized, open-label design with 1017 women participating, who were monitored during first-line aromatase inhibitor therapy.
- The co-primary endpoints included progression-free survival after switching treatment and assessing serious adverse events, with the trial's results aimed at improving treatment strategies for this patient population.
Background: Patients with HER2-positive breast cancer (HER2 + BC) develop central nervous system metastases twice as often as patients with luminal HER2-negative breast cancer. Leptomeningeal progression results in a drastically altered prognosis with limited therapeutic options. This phase II study was conducted to assess the efficacy of intrathecal (IT) trastuzumab in HER2 + BC patients with leptomeningeal metastasis (LM), based on a phase I dose-escalation study that had determined the recommended weekly dose of 150 mg for phase II.
View Article and Find Full Text PDFBackground: Olaparib has significantly improved outcome and patient-centered endpoints in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer (PSOC). Specific information on efficacy and safety of olaparib for older patients appears of special interest.
Methods: 295 patients from the SOLO2 trial randomly assigned to olaparib or placebo were categorized according to age-cutoff at 65 years.
Background: Gynecological carcinosarcomas are rare and aggressive diseases, with a poor prognosis. The rarity of these tumors explains the lack of robust and specific data available in the literature. The objective of this study was to investigate the impact of initial adjuvant treatment and recurrent therapeutic strategies.
View Article and Find Full Text PDFDevelopment of high-throughput technologies helped to decipher tumor genomic landscapes revealing actionable molecular alterations. We aimed to rank the level of evidence of recurrent actionable molecular alterations in head and neck squamous cell carcinoma (HNSCC) on the basis of the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) to help the clinicians prioritize treatment. We identified actionable alterations in 33 genes.
View Article and Find Full Text PDFBackground: Pembrolizumab has efficacy in programmed death ligand 1 (PD-L1)-positive metastatic or unresectable cervical cancer that has progressed during chemotherapy. We assessed the relative benefit of adding pembrolizumab to chemotherapy with or without bevacizumab.
Methods: In a double-blind, phase 3 trial, we randomly assigned patients with persistent, recurrent, or metastatic cervical cancer in a 1:1 ratio to receive pembrolizumab (200 mg) or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy and, per investigator discretion, bevacizumab.
Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are two cancer-derived blood biomarkers that inform on patient prognosis and treatment efficacy in breast cancer. We prospectively evaluated the clinical validity of quantifying both CTCs (CellSearch) and ctDNA (targeted next-generation sequencing). Their combined value as prognostic and early monitoring markers was assessed in 198 HER2-negative metastatic breast cancer patients.
View Article and Find Full Text PDFChanges in the oral microbiome, particularly Fusobacterium nucleatum, are associated with oral squamous cell carcinoma (OSCC). F. nucleatum has been reported to modulate local immunity in cancers.
View Article and Find Full Text PDFBackground: Following the PALOMA-3 study results, the combination of palbociclib, a CDK4/6 inhibitor, with fulvestrant, a selective estrogen receptor degrader, has become a standard therapy in women with estrogen receptor-positive (ER+) HER2-negative (HER2-) metastatic breast cancer (MBC). Palbociclib has been shown to increase the progression-free survival (PFS) overall but no predictive biomarker of palbociclib efficacy has been validated so far. We thus evaluated whether early changes of circulating tumor DNA (ctDNA) levels are associated with palbociclib plus fulvestrant efficiency.
View Article and Find Full Text PDFBackground: Bevacizumab is approved in combination with chemotherapy for the treatment of ovarian cancer, either in first-line therapy or for patients with recurrent disease not previously treated with the same drug. We aimed to test the value of continuing bevacizumab beyond progression after first-line treatment with the same drug.
Methods: In our open-label, randomised, phase 3 trial done at 82 sites in four countries, we enrolled women (aged ≥18 years) who had previously received first-line platinum-based therapy including bevacizumab, and had recurrent (≥6 months since last platinum dose), International Federation of Gynaecology and Obstetrics stage IIIB-IV ovarian cancer with an Eastern Cooperative Oncology Group performance status 0-2.
Background: Cancer-related microangiopathic haemolytic anaemia (MAHA) is a rare but life-threatening paraneoplastic syndrome. Only single cases or small series have been reported to date. We set up a retrospective multicentre study focusing on breast cancer-related MAHA.
View Article and Find Full Text PDFThe prospective multicenter COMET trial followed a cohort of 306 consecutive metastatic breast cancer patients receiving bevacizumab and paclitaxel as first-line chemotherapy. This study was intended to identify and validate reliable biomarkers to better predict bevacizumab treatment outcomes and allow for a more personalized use of this antiangiogenic agent. To that end, we aimed to establish risk scores for survival prognosis dichotomization based on classic clinico-pathological criteria combined or not with single nucleotide polymorphisms (SNPs).
View Article and Find Full Text PDFBackground: Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality with infection by human papilloma virus (HPV) being the most important risk factor. We analysed the association between different viral integration signatures, clinical parameters and outcome in pre-treated CCs.
Methods: Different integration signatures were identified using HPV double capture followed by next-generation sequencing (NGS) in 272 CC patients from the BioRAIDs study [NCT02428842].