S. Oudard's research while affiliated with Centre Hospitalier Lyon Sud and other places

Publications (890)

Article
Purpose: CD70 is a costimulatory molecule known to activate CD27-expressing T cells. CD27-CD70 interaction leads to the release of soluble CD27 (sCD27). Clear cell renal cell carcinoma (ccRCC) expresses the highest levels of CD70 among all solid tumors; however, the clinical consequences of CD70 expression remain unclear. Experimental design: Tu...
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Background The first interim analysis of the KEYNOTE-564 study showed improved disease-free survival with adjuvant pembrolizumab compared with placebo after surgery in patients with clear cell renal cell carcinoma at an increased risk of recurrence. The analysis reported here, with an additional 6 months of follow-up, was designed to assess longer-...
Article
Background Pembrolizumab and olaparib have shown single-agent activity in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC). Objective To evaluate the efficacy and safety of pembrolizumab plus olaparib in mCRPC. Design, setting, and participants Cohort A of the phase 1b/2 KEYNOTE-365 study enrolled patients...
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MiTF/TFE translocation renal cell carcinoma (tRCC) is a rare and aggressive subtype of RCC representing the most prevalent RCC in the pediatric population (up to 40%) and making up 4% of all RCCs in adults. It is characterized by translocations involving either TFE3 (TFE3-tRCC), TFEB (TFEB-tRCC) or MITF, all members of the MIT family (microphthalmi...
Article
Microabstract As proton pump inhibitors (PPI) were shown to impact the effectiveness of immune checkpoint inhibitors (ICI) in lung and bladder cancers, we sought to evaluate the effect of PPIs on the outcomes patients with metastatic renal cell carcinoma (mRCC) treated with ICI. Introduction Proton pump inhibitors (PPI) may influence the gut micro...
Article
Context: Polymerase epsilon (POLE) gene missense hotspot mutations can generate pathogenic (p) proofreading defects resulting in hypermutated genomic profiles. Aim: Determine the prevalence, genomic consequences and immunotherapy sensitivity of advanced POLE mutated tumors according to mutation site, primary tumor and tumor mutational burden (TMB)....
Article
Introduction: Mammalian target of rapamycin (mTOR) inhibitors-associated pneumonitis (mTOR-IP) has long been described in solid organ recipients (T) patients but more recently in cancer (K) patients. Its overall characteristics have never been compared between these 2 populations. The aim of this study was to compare them in terms of presentation,...
Article
Background: Germline and somatic mutations in DNA damage repair genes (DDRg) are now recognized as new biomarkers for the management of metastatic prostate cancers (mPC). We evaluate the frequency of germline DDRg mutations among French mPC patients of European and African ancestries. Methods: Targeted next-generation sequencing of 21 DDRg was p...
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Background and purpose Chemotherapy-induced neutropenia and neutrophil-to-lymphocyte ratio (NLR) are potentially useful prognostic markers in patients with metastatic castration-resistant prostate cancer (mCRPC). This post hoc analysis investigated whether these markers can be utilized for dose considerations and evaluated the prognostic impact of...
Article
Nivolumab and Cabozantinib are approved agents in mRCC patients after sunitinib/pazopanib (TKI) failure. However, the optimal sequence, Cabozantinib then Nivolumab (CN) or Nivolumab then Cabozantinib (NC), is still unknown. The CABIR study aimed to identify the optimal sequence between CN and NC after frontline VEGFR‐TKI. In this multicenter retros...
Preprint
Immune checkpoint inhibitors have revolutionized the treatment of patients with clear-cell renal carcinomas. Although, analyses of transcriptome, genetic alterations, and the tumor microenvironment have shed light into mechanisms of response and resistance to these agents, the role of epigenetic alterations in this process remains fully unknown. He...
Article
The field of clear cell renal cell carcinoma (ccRCC) has undergone major changes in the last decade, both in terms of the understanding of the mechanisms of oncogenesis and the role of the tumor microenvironment in anti-tumor immunity, as well as in therapeutic developments. After the era of tyrosine kinase inhibitors (TKIs) targeting VEGFR and the...
Article
Missense mutations in the polymerase epsilon (POLE) gene have been reported to generate proofreading defects resulting in an ultramutated genome and to sensitize tumors to checkpoint blockade immunotherapy. However, many POLE-mutated tumors do not respond to such treatment. To better understand the link between POLE mutation variants and response t...
Article
Background We previously reported a 35-gene expression classifier identifying four clear-cell renal cell carcinoma groups (ccrcc1 to ccrcc4) with different tumour microenvironments and sensitivities to sunitinib in metastatic clear-cell renal cell carcinoma. Efficacy profiles might differ with nivolumab and nivolumab–ipilimumab. We therefore aimed...
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Collecting duct carcinoma (CDC) and renal medullary carcinoma (RMC) are two rare subtypes of kidney cancer with a poor prognosis in the metastatic setting. Beyond first-line treatment, there are no standard-of-care therapies. This retrospective study assessed the efficacy of treatments after first-line chemotherapy in 57 patients with metastatic (m...
Article
Objectives: To validate a deep learning (DL) algorithm for measurement of skeletal muscular index (SMI) and prediction of overall survival in oncology populations. Methods: A retrospective single-center observational study included patients with metastatic renal cell carcinoma between 2007 and 2019. A set of 37 patients was used for technical va...
Article
142 Background: In ACIS, APA + AAP improved radiographic progression-free survival in mCRPC vs AAP; difference in overall survival (OS) was not statistically significant. We report a prespecified analysis of androgen receptor (AR) or non-AR genomic/transcriptional aberrations, known to be associated with poor prognosis, and their associations with...
Article
540 Background: The 3-arm, open-label, phase 3 KEYNOTE-361 study (NCT02853305) evaluated first-line pembro ± chemo vs chemo in advanced UC regardless of PD-L1 status. The trial did not meet its primary end points of superior PFS and OS with pembro + chemo vs chemo and thus analysis of pembro monotherapy (mono) vs chemo was exploratory. We explored...
Article
73 Background: In phase 3 placebo (PBO)-controlled studies, addition of APA to androgen deprivation therapy (ADT) improved overall survival, resulted in rapid and deep PSA declines, and reduced risk of disease progression while preserving health-related quality of life (HRQoL) in nonmetastatic castration-resistant prostate cancer (nmCRPC; SPARTAN)...
Article
348 Background: Glandular metastases (GMs) (adrenal, pancreas, thyroid, ovary, breast, or prostate) are rare in mccRCC. Several studies have observed significantly longer overall survival (OS) for GM patients treated with anti-angiogenic therapy. This study assesses outcomes from mccRCC treated with nivolumab with or without GMs. Methods: The GETUG...
Article
521 Background: First-line treatment with pembrolizumab (pembro) monotherapy has shown durable clinical activity in selected patients (pts) with advanced/unresectable or metastatic urothelial carcinoma (UC). In a pooled population of pts with advanced UC from the single-arm phase 2 KEYNOTE-052 (NCT02335424) and the randomized, open-label, phase 3 K...
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Introduction: Immune checkpoint inhibitors (ICI) have been approved for front-line therapy in metastatic renal cell carcinoma (mRCC). However, progressive disease often occurs and subsequent therapies are needed. ICI rechallenge may be an option, but there is a lack of data regarding efficacy and prognostic factors. We assessed efficacy of ICI rec...
Article
Importance: DCVAC/PCa is an active cellular immunotherapy designed to initiate an immune response against prostate cancer. Objective: To evaluate the efficacy and safety of DCVAC/PCa plus chemotherapy followed by DCVAC/PCa maintenance treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). Design, setting, and partic...
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Background: In metastatic prostate cancer (PCa) patients, androgen-deprivation therapy (ADT) combined with chemotherapy or next-generation androgen receptor targeted agents is a new standard treatment. The objective of the present study is to assess longitudinal PSA kinetics during treatment using mathematical modeling, to identify the modeled PSA...
Article
The presence of intratumoral tertiary lymphoid structures (TLS) is associated with positive clinical outcomes and responses to immunotherapy in cancer. Here, we used spatial transcriptomics to examine the nature of B cell responses within TLS in renal cell carcinoma (RCC). B cells were enriched in TLS, and therein, we could identify all B cell matu...
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Cabozantinib inhibits multiple receptor tyrosine kinases, including the TAM kinase family, and may enhance response to immune checkpoint inhibitors. One cohort of the ongoing Phase Ib COSMIC-021 study (NCT03170960) evaluating cabozantinib plus the PD-L1 inhibitor atezolizumab in men with metastatic castration-resistant prostate cancer (mCRPC) that...
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Background The CARD study demonstrated superiority of cabazitaxel over abiraterone/enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who received prior docetaxel and progressed ≤12 months on the alternative androgen-receptor-targeted agent (ARTA). The objective was to compare characteristics and treatment pattern...
Article
Introduction Les inhibiteurs de mTOR (mammalian target of rapamycin), initialement utilisés comme immunosuppresseurs en transplantation d’organe solide, ont vu leurs indications s’étendre au domaine de l’oncologie médicale en raison de leurs propriétés antitumorales. La toxicité pulmonaire des inhibiteurs de mTOR est rapportée dans les deux indicat...
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The modulation of subpopulations of pro-angiogenic monocytes (VEGFR-1+CD14 and Tie2+CD14) was analyzed in an ancillary study from the prospective PazopanIb versus Sunitinib patient preferenCE Study (PISCES) (NCT01064310), where metastatic renal cell carcinoma (mRCC) patients were treated with two anti-angiogenic drugs, either sunitinib or pazopanib...
Article
Background Apalutamide plus androgen deprivation therapy (ADT) significantly improved metastasis-free survival (MFS), overall survival (OS), and time to prostate-specific antigen (PSA) progression in the placebo-controlled SPARTAN study of high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC). Objective To assess the relationships...
Article
Background: Patients with von Hippel-Lindau (VHL) disease have a high incidence of renal cell carcinoma owing to VHL gene inactivation and constitutive activation of the transcription factor hypoxia-inducible factor 2α (HIF-2α). Methods: In this phase 2, open-label, single-group trial, we investigated the efficacy and safety of the HIF-2α inhibi...
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IntroductionApalutamide and darolutamide are next-generation androgen receptor inhibitors that have demonstrated superior efficacy compared to placebo in men with non-metastatic castration-resistant prostate cancer (nmCRPC) receiving androgen deprivation therapy (ADT). In the absence of head-to-head studies, the present study sought to indirectly c...
Article
Background Two phase II trials (NCT00688753 and NCT00541008) reported efficacy data of sunitinib and everolimus in first-line treatment of metastatic papillary renal cell carcinoma (mpRCC). Although most patients receive sunitinib or a mammalian target of rapamycin (mTOR) inhibitor in first- and second-line treatment, the optimal strategy remained...
Article
Background CD70, a costimulatory molecule on antigen presenting cells, is known to activate CD27-expressing T cells. CD27-CD70 interaction leads to the release of soluble CD27 (sCD27). However, persistent interaction of CD27 and CD70 such as in chronic infection may exhaust the T cell pool and promote apoptosis. Surprisingly, our analysis based on...
Article
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Background In SPARTAN, apalutamide improved metastasis-free and overall survival for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) with a prostate-specific antigen doubling time of ≤10 mo. Objective We evaluated health-related quality of life (HRQoL) at the final analysis of the SPARTAN study. Intervention Patients rec...
Article
Background The majority of patients with metastatic castration-resistant prostate cancer (mCRPC) will have disease progression of a uniformly fatal disease. mCRPC is driven by both activated androgen receptors and elevated intratumoural androgens; however, the current standard of care is therapy that targets a single androgen signalling mechanism....
Article
Background: Patients with renal-cell carcinoma who undergo nephrectomy have no options for adjuvant therapy to reduce the risk of recurrence that have high levels of supporting evidence. Methods: In a double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with clear-cell renal-cell carcinoma who were at high risk for recurre...
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Introduction Cabazitaxel multiple rechallenges may be a treatment option in heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC) who had a good initial response to cabazitaxel and who are still fit to receive it. Our objective was to assess the efficacy and toxicity of multiple rechallenges. Patients and methods...
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Minimally invasive approaches to detect residual disease after surgery are needed to identify patients with cancer who are at risk for metastatic relapse. Circulating tumour DNA (ctDNA) holds promise as a biomarker for molecular residual disease and relapse1. We evaluated outcomes in 581 patients who had undergone surgery and were evaluable for ctD...
Article
Primary tumour response may impact therapeutic strategies in metastatic renal cell carcinoma (mRCC) but remains unknown in the era of immune checkpoint inhibitors. We aimed to describe the response of the primary tumour in patients who did not undergo upfront cytoreductive nephrectomy (uCN) and were treated with nivolumab in the GETUG-AFU-26 NIVORE...
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Background Better blood tests to elucidate the behaviour of metastatic castration-resistant prostate cancer (mCRPC) are urgently needed to drive therapeutic decisions. Plasma cell-free DNA (cfDNA) comprises normal and circulating tumour DNA (ctDNA). Low-pass whole-genome sequencing (lpWGS) of ctDNA can provide information on mCRPC behaviour. Objec...
Article
Background: The CARMENA trial in patients with metastatic renal cell carcinoma (mRCC) demonstrated that treatment with sunitinib alone was noninferior to cytoreductive nephrectomy (CN) followed by sunitinib (nephrectomy-sunitinib). Objective: The objective of this study was to provide updated overall survival (OS) outcomes of CARMENA and assess...
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The complement system plays a complex role in cancer. In clear cell renal cell carcinoma (ccRCC), local production of complement proteins drives tumor progression, but the mechanisms by which they do this are poorly understood. We found that complement activation, as reflected by high plasma C4d or as C4d deposits at the tumor site, was associated...
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The complement system is a powerful and druggable innate immune component of the tumor microenvironment. Nevertheless, it is challenging to elucidate the exact mechanisms by which complement affects tumor growth. In this study, we examined the processes by which the master complement regulator factor H (FH) affects clear cell renal cell carcinoma (...
Article
4555 Background: Inactivation of VHL leads to aberrant stabilization and accumulation of HIF-2α, which drives tumor growth. Patients (pts) with VHL disease are at risk for ccRCC, pancreatic neuroendocrine tumors (pNETs), and hemangioblastomas. Repeated surgeries are often needed to control ccRCC and other VHL disease manifestations. Prior results o...
Article
5037 Background: In the double-blind PBO-controlled ACIS study, investigator-assessed radiographic progression-free survival (rPFS) was significantly improved with APA + AAP vs PBO + AAP in chemo-naive mCRPC, with no significant new safety signals (Rathkopf ASCO GU 2021). Among prespecified subgroups, efficacy and safety were explored in two diffic...
Article
5546 Background: The EWOC-1 trial compared Carboplatin monotherapy (C mono) to two different Carboplatin + Paclitaxel (CP) regimens (weekly or 3-weekly) in vulnerable elderly patients treated for advanced ovarian cancers (OC). This study was closed prematurely because of a worse outcome in the C mono group. Both CP regimens were equivalent in terms...
Article
e16566 Background: Nivolumab monotherapy (N) is a standard of care for patients with metastatic clear cell renal cell carcinoma (ccRCC) after failure of antiangiogenic therapies. IMDC criteria is the established prognostic model in anyline of systemic treatment including with N. While liver, bone and brain have been reported to convey a dismal prog...
Article
TPS5086 Background: In cancer cells, the cyclin-dependent kinases 4 and 6 (CDK4 & 6)/retinoblastoma protein (Rb) pathway is commonly altered, resulting in uncontrolled cell cycle entry and proliferation. CDK4 & 6 inhibitors represent a major advance in the management of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negat...
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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...
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PurposeAdvancements in the diagnosis and treatment of prostate cancer (PC) have rapidly progressed through the past years. Various factors should be taken into account while treating individual patients to ensure optimal and careful decision making. The purpose of this consensus review is to summarize the current practice patterns when managing pat...
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In the last few years, the standard of care for metastatic clear cell renal cell carcinoma (mccRCC) has changed dramatically with the emergence of the immune checkpoint inhibitors (ICI): anti-PD(L)-1 used as a monotherapy or as in combination either with an anti CTLA-4 or with an anti-angiogenic molecule (VEGFR tyrosine kinase inhibitor (TKI)). The...
Article
Background PD-1 and PD-L1 inhibitors are active in metastatic urothelial carcinoma, but positive randomised data supporting their use as a first-line treatment are lacking. In this study we assessed outcomes with first-line pembrolizumab alone or combined with chemotherapy versus chemotherapy for patients with previously untreated advanced urotheli...
Article
Background The optimal therapeutic strategies for patients with metastatic hormone-sensitive prostate cancer (mHSPC) followed by metastatic castrate-resistant prostate cancer (mCRPC), in terms of cost and effectiveness remains unknown. This study aims to compare the cost-effectiveness of various potential strategies, from the start of first-line tr...