Publications by authors named "Pernelle Lavaud"

Background: The MOVIE phase I/II trial (NCT03518606) evaluated the safety and antitumor activity of durvalumab and tremelimumab combined with metronomic oral vinorelbine in patients with advanced tumors. We present the results of the recurrent advanced cervical cancer cohort.

Methods: Patients received tremelimumab (intravenously, 75 mg, every four weeks (Q4W); four cycles max) plus durvalumab (intravenously, 1,500 mg, Q4W; 26 cycles max) and metronomic oral vinorelbine (40 mg, every three weeks (3QW)) until disease progression.

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  • Metastatic urothelial carcinoma (mUC) is a dangerous cancer with few treatment options, and its genetic makeup is not fully understood unlike non-metastatic urothelial carcinoma (UC).
  • A study analyzing genetic data from 111 mUC biopsies found that common genetic changes are similar to those seen in primary UC and highlighted mutational signatures related to APOBEC, platinum sensitivity, and homologous recombination deficiency.
  • The research revealed that a significant portion of mUC patients have potential therapeutic targets, with the most common being FGFR3, ERBB2, TSC1, and PIK3CA, and noted that certain genes like NECTIN4 and TACSTD2 are consistently highly expressed across different
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The recent advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint blockers (ICBs) in early-stage non-small cell lung cancer (NSCLC) has dramatically modified treatment strategies by improving the prognosis in this setting. Osimertinib and alectinib, both TKIs, have shown significant improvements in outcomes for patients with resected - and -positive NSCLC, respectively, changing the standard of care in these subgroups. More recently, the LAURA trial showed the efficacy of osimertinib after chemoradiotherapy in patients with unresectable stage III NSCLC harboring mutations.

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Background: The efficacy of front-line pembrolizumab has been established in studies that limit treatment duration to 2 years, but decision to stop pembrolizumab after 2 years is often at physician's discretion. ATHENA is a retrospective cohort study using a comprehensive administrative database aimed firstly at exploring the optimal duration of pembrolizumab and secondly real-life prognosis factors in patients with advanced non-small cell lung cancer (NSCLC).

Methods: Using the French National Health Insurance database (SNDS), we identified patients with incident lung cancer in France from 2015 to 2022.

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Background: Immune checkpoint inhibitors (ICIs) improve overall survival (OS) in advanced/metastatic urothelial cancer (a/mUC) patients. Preliminary evidence suggests a prognostic role of inflammatory biomarkers in this setting. We aimed to develop a disease-specific prognostic inflammatory index for a/mUC patients on ICIs.

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  • The study examines the Lung Immune Prognostic Index (LIPI) to see if it can predict survival in patients with metastatic renal cell carcinoma (mRCC).
  • LIPI categorizes patients into groups based on specific blood markers, and results show that those with a better LIPI score have significantly longer overall and progression-free survival.
  • The findings indicate that LIPI can be a useful prognostic tool for mRCC patients regardless of the type of treatment they receive, whether it’s immune checkpoint inhibitors or antiangiogenic therapy.
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  • This review discusses advancements in treatments for metastatic castration-sensitive prostate cancer (mCSPC), highlighting systematic treatment improvements over the past decade.
  • Recent findings show that combining treatments like docetaxel and second-generation androgen receptor pathway inhibitors with androgen deprivation therapy (ADT) leads to better survival rates for patients.
  • Ongoing trials are investigating the role of radiotherapy, local therapies, and biomarkers in enhancing treatment decisions, though the effectiveness for metastatic relapse cases is still being determined.
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Background: Genomic studies have identified new subsets of aggressive prostate cancer (PCa) with poor prognosis (eg, neuroendocrine prostate cancer [NEPC], PCa with DNA damage response [DDR] alterations, or PCa resistant to androgen receptor pathway inhibitors [ARPIs]). Development of novel therapies relies on the availability of relevant preclinical models.

Objective: To develop new preclinical models (patient-derived xenograft [PDX], PDX-derived organoid [PDXO], and patient-derived organoid [PDO]) representative of the most aggressive variants of PCa and to develop a new drug evaluation strategy.

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Introduction: DNA damage repair genes are altered in 20-35% of metastatic castration-resistant prostate cancer (mCRPC). Poly-ADP (Adénosine Diphosphate)-ribose polymerase inhibitors (PARPi) showed significant activity for these selected tumors, especially with homologous recombination repair (HRR) deficiency. These alterations could also predict platinum sensitivity.

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  • The study investigates the reasons why not all men with metastatic castration-resistant prostate cancer (mCRPC) respond to androgen receptor axis inhibitors (ARPI) like enzalutamide and abiraterone acetate.
  • Researchers conducted whole-exome and RNA sequencing to identify genetic factors related to both primary and acquired resistance in 59 mCRPC patients, along with biopsies from 18 patients who exhibited resistance.
  • Findings revealed no strong single-gene variations linked to initial resistance, but a combination of low androgen receptor activity and certain pathway alterations were associated with primary resistance, while acquired resistance was tied to subclonal evolution and changes in AR-related genes.
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Introduction: Serum prostate specific antigen (PSA) is a well-known prognostic parameter in men with prostate cancer. The treatment of men with very high PSA values and apparently no detectable metastases is not fully established.

Patients And Methods: Ancillary analysis from the GETUG 12 phase 3 trial.

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Introduction: The role of local ablative treatments, including stereotactic body radiotherapy (SBRT), is an area of active research in oligometastatic patients. Small cell lung cancer (SCLC) has a poor prognosis, with common diffuse metastatic evolution. We evaluated the outcomes after SBRT in uncommon oligoprogressive/oligorecurrent SCLC presentation.

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Few prognostic factors have been identified in patients with metastatic urothelial carcinoma (mUC) treated with immune checkpoint inhibitors (ICIs). The Lung Immune Prognostic Index (LIPI) was associated with clinical outcomes for ICIs in several tumor types. We aim to assess the value of the LIPI in patients with mUC treated with ICIs.

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Background: We aimed to determine whether immune checkpoint inhibitors (ICI) time-of-day infusion might influence the survival of patients with advanced non-small cell lung cancer (NSCLC).

Methods: We retrospectively analysed patients who received single-agent anti-PD-(L)1 therapy in any line between 2016 and 2021. We calculated by Cox regression models the association between the proportion of ICI infusions received after 16:30h and overall survival (OS) and progression-free survival (PFS).

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Background: Generalised oedema was occasionally reported associated with immune checkpoint inhibitors (ICPIs). The purpose of this study is to investigate immune-related generalised oedema (ir-GE) drug related to ICPI, through frequency, clinical and pathological characteristics, and patient's outcome.

Patients And Methods: Objectives of the study were to report on ir-GE associated with ICPI to define frequency, associated signs and symptoms, pathological characteristics, severity, and response to corticosteroids.

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Background: EGFRm represent 15% of advanced NSCLC in European patients. LB for molecular profiling offers a non-invasive alternative to tissue. cdPCR is a high-sensitive and low-cost LB to detect molecular alterations.

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Up to 25% of patients with metastatic prostate cancer present with germline or somatic DNA damage repair alterations, some of which are associated with aggressive disease and poor outcomes. New data have brought poly(ADP-ribose) polymerase (PARP) inhibitors into sharp focus in the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Olaparib improved survival after at least one new hormonal therapy (NHT) in a cohort of patients harboring BRCA1, BRCA2 or ATM mutations in the PROfound trial, while rucaparib, talazoparib and niraparib demonstrated compelling activity in phase II trials.

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  • The study investigates how memory T cells respond to the SARS-CoV-2 virus and its variants, focusing on their link to protection against COVID-19 in healthy and cancer patients.
  • Findings suggest that an imbalance in immune responses, particularly between type 1 and type 2 cytokines, increases vulnerability to the virus, especially in individuals with specific deficiencies in T helper 1 (Th1) cells.
  • Current vaccines primarily trigger Th1 responses effectively against the original virus strain, highlighting the need for future vaccines to target T-cell responses against the receptor binding domain of new variants.
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Gatekeeper mutations are identified in only 50% of the cases at resistance to Anaplastic Lymphoma Kinase (ALK)-tyrosine kinase inhibitors (TKIs). Circulating tumor cells (CTCs) are relevant tools to identify additional resistance mechanisms and can be sequenced at the single-cell level. Here, we provide in-depth investigation of copy number alteration (CNA) heterogeneity in phenotypically characterized CTCs at resistance to ALK-TKIs in ALK-positive non-small cell lung cancer.

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Introduction: Less than one-third of bladder cancers are non-pure urothelial carcinoma [with variant histological (VH) or non-urothelial carcinoma (non-UC)] for which no treatment guidelines are available. We aim to evaluate the efficacy of systemic treatments in VH or non-UC bladder cancers.

Materials: Multicenter retrospective analysis of patients treated for advanced or metastatic VH or non-UC bladder cancers.

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Immunotherapy, which consists in using molecules targeting the immune system, has existed for many years in oncology (vaccines, interleukins, monoclonal antibodies) but has recently expanded due to the development of immune checkpoint inhibitors. These monoclonal antibodies help to restore the immunity against cancer by specifically targeting some immune checkpoints such as CTLA-4, PD-1 and PD-L1. Furthermore, in oncology, it is common to use systemic corticosteroids in the management of symptoms linked to the natural history of the disease (pain, spinal cord compression, cerebral edema) and toxicities linked to anticancer treatment.

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Background: ROS1 tyrosine kinase inhibitors (TKIs) have showed activity and efficacy in -rearranged non-small cell lung cancer (NSCLC). In the clinical practice, besides the utilization of crizotinib, less is known about the best treatment strategies involving additional, new-generation TKIs for the sequential treatment of ROS1-positive NSCLC patients.

Case Presentation: A patient suffering from a -rearranged lung adenocarcinoma, after receiving cisplatin-pemetrexed chemotherapy, was treated with entrectinib, a new-generation ALK/ROS1/NTRK inhibitor.

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