Michel Ducreux

Institut Gustave Roussy | IGR · Department of Adult Medicine

Background Chemotherapy for metastatic pancreatic adenocarcinoma (PDAC) primarily relies on FOLFIRINOX (LV5FU- irinotecan – Oxaliplatine) and Gemcitabine – Nab-Paclitaxel in the first-line setting. However, second-lines remain less well-defined and there is limited data regarding third-line treatments. The objective of our study was to determine th...

Introduction: The Phase III IMbrave150 study established atezolizumab + bevacizumab as the global standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis examined the impact of bevacizumab interruption due to bevacizumab adverse events of special interest (AESIs). Methods: Patients in IMbrave150 who...

Background Patient Derived Organoids (PDOs) emerged as the best technology to develop ex vivo tumor avatars. Whether drug testing on PDOs to identify efficient therapies will bring clinical utility by improving patient survival remains unclear. To test this hypothesis in the frame of clinical trials, PDO technology faces three main challenges to be...

Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of death by cancer worldwide. Mostly diagnosed with locally advanced or metastatic disease, patients lack treatment options. Gene alterations (GAs) are frequently observed in PDAC, some of which are considered for molecular targeted therapies (MTTs), with potential clin...

Biliary tract cancers (BTCs) are rare tumours, most often diagnosed at an unresectable stage, associated with poor prognosis, with a 5-year survival rate not exceeding 10%. Only first- and second-line treatments are well codified with the combination of cisplatin-gemcitabine chemotherapy and immunotherapy followed by 5-FU and oxaliplatin chemothera...

Background: Despite improvements in characterization of CRC heterogeneity, appropriate risk stratification tools are still lacking in clinical practice. This study aimed to elucidate the primary tumor transcriptomic signatures associated with distinct metastatic routes. Methods: Primary tumor specimens obtained from CRC patients with either isol...

Introduction: Activating RAS gene mutations occur in approximately 55% of patients with metastatic colorectal cancer (mCRC) and are associated with poorer clinical outcomes due to epidermal growth factor receptor (EGFR) blockade resistance. Combined EGFR and mitogen-activated protein kinase (MEK) inhibition may extend response to EGFR inhibition a...

Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of death by cancer worldwide. Mostly diagnosed with locally advanced or metastatic disease, patients lack treatment options. Gene alterations (GAs) are frequently observed in PDAC; some of which are considered for molecular targeted therapies (MTTs), with potential clini...

PURPOSE The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus o...

Capecitabine is an orally administered fluoropyrimidine carbamate antineoplastic agent, widely used to treat different tumor types. Eye toxicity is not well established with this type of drug. Here, we report the case of a 57-year-old man with a low rectal cancer whose vision decreased 3 weeks after starting a daily treatment of capecitabine and ra...

This article summarises expert discussion on the management of patients with hepatocellular carcinoma (HCC), which took place during the 24th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, July 2022. A multidisciplinary approach is mandatory to ensure an optimal diagnosis and staging of HCC, planning of curative and therapeutic option...

Background: HER2 is overexpressed or amplified in a subset of biliary tract cancer. Zanidatamab, a bispecific antibody targeting two distinct HER2 epitopes, exhibited tolerability and preliminary anti-tumour activity in HER2-expressing or HER2 (also known as ERBB2)-amplified treatment-refractory biliary tract cancer. Methods: HERIZON-BTC-01 is a...

e18542 Background: The management of rare and/or complex cancers between patients living in metropolitan France and those living overseas remains unequal. Herein, medical transfer to metropolitan France is required in about 20% of overseas-living patients and is often experienced as an additional source of distress, which requires multidisciplinary...

4057 Background: 10-20% of GC are HER-2 positive. The role of perioperative anti-HER2-directed treatment is yet undefined. Methods: This randomized, open-label phase II-trial investigates the benefit of combining T alone or with P and perioperative CT for GC and EGJC. Between 2015 and 2021,172 of a planned 215 patients (pts) with centrally confirme...

4008 Background: For patients (pts) with locally advanced/metastatic BTC who progress after first-line treatment (tx), standard tx offers limited clinical benefit with modest improvement in survival. HER2-targeted therapies have improved survival in breast and gastric cancer, but there is no approved HER2-targeted therapy for BTC. Zanidatamab (zani...

Background: There is a paucity of effective systemic therapy options for patients with advanced, chemotherapy-refractory colorectal cancer. We aimed to evaluate the efficacy and safety of fruquintinib, a highly selective and potent oral inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3, in patients with heavily pretrea...

Purpose of review: Pancreatic cancer treatment remains a challenging problem for surgeons and oncologists. This review aims to summarize the current advances on adjuvant and neoadjuvant treatment approaches for resectable pancreatic cancer. Recent findings: Recent phase III randomized trials of adjuvant therapy showed improvement of overall surv...

Background The current model of clinical drug development in oncology displays major limitations due to a high attrition rate in patient enrollment in early phase trials and a high failure rate of drugs in phase III studies. Objective Integrating transcriptomics for selection of patients has the potential to achieve enhanced speed and efficacy of...

Introduction: Atezolizumab + bevacizumab showed survival benefit in patients with unresectable hepatocellular carcinoma (HCC) vs sorafenib in the Phase III IMbrave150 study. This exploratory analysis examined the prognostic impact of baseline albumin-bilirubin (ALBI) score. Methods: Patients with treatment-naïve unresectable HCC, ≥1 measurable unt...

Background: Key molecular alterations (MA) of neuroendocrine neoplasm (NEN) of various grade/primaries have been described but the applicability of molecular profiling (MP) for precision medicine in NEN remains to be demonstrated. Methods: We conducted a retrospective study of all patients with metastatic NEN who had MP on tumour tissue at Gusta...

Simple Summary Hypoxia is a key feature of the tumor microenvironment involved in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC). In this review we will highlight hypoxia’s integral role in shaping genomic instability and the tumor immune microenvironment in this disease. We will further present strategies currently being investigated...

TPS279 Background: Amivantamab, a fully human EGFR and MET bispecific antibody, has shown clinical activity against tumors with primary activating EGFR mutations, EGFR resistance mutations, or MET pathway activation. Amivantamab has demonstrated activity in both EGFR- and MET-driven non-small cell lung cancer, with preclinical evidence demonstratin...

750 Background: KRAS mutation is the most common molecular alteration (MA) in pancreatic adenocarcinoma (PDAC), and only 8-10% of patients (pts) harbor KRAS wild-type tumors (WT). This study describes clinical and molecular features of KRAS WT PDAC and compares it to mutant KRAS (m KRAS) PDAC. Methods: A retrospective chart review of clinical/molec...

809 Background: Peritoneal carcinomatosis (PC) is a common manifestation in gastro-intestinal (GI) cancers.10-20 % of patients (pts) will present isolated, unresectable peritoneal disease with poor prognosis. In the past years, circulating tumor DNA (ctDNA) has emerged as a novel and less invasive biomarker for molecular diagnosis and disease monit...

141 Background: Treatment for patients (pts) with metastatic colorectal cancer (mCRC) with unresectable liver metastases (mets) is usually chemotherapy (CT) +/- local ablative treatments. Immunotherapy (IO) effect is disappointing in mCRC with pMMR status so testing strategies to promote immune activation is key. Previous studies show that local ab...

538 Background: Treatment with atezo + bev has been approved globally for patients with unresectable HCC who have not received prior systemic therapy, based on results from the Phase 3 IMbrave150 study (NCT03434379, Finn NEJM 2020 and Cheng J Hepatol 2022). According to Phase 1b study data (Lee Lancet Oncol 2020), when combined with atezo, bev has...

Purpose: MODUL is an adaptable, signal-seeking trial of biomarker-driven maintenance therapy following first-line induction treatment in patients with metastatic colorectal cancer (mCRC). We report findings from Cohorts 1 (BRAFmut), 3 (human epidermal growth factor 2 [HER2]+) and 4 (HER2‒/high microsatellite instability, HER2‒/microsatellite stabl...

This cohort study assesses the outcome of oxaliplatin desensitization for patients with gastrointestinal cancers who experienced hypersensitivity reactions after oxaliplatin infusion.

Purpose Kinase inhibitors (KI) and antibodies targeting the VEGF pathway are approved in a broad spectrum of cancers and associated with an increased risk of bleeding and thromboembolic events (TE). The use of direct oral anticoagulants (DOACs) apixaban and rivaroxaban is increasing in cancer patients, but limited data are available for patients re...

Introduction Intra-arterial hepatic (IAH) treatment has shown promising results in the management of patients with unresectable colorectal liver metastases (CRLM) the prognosis of which is poor. Bevacizumab adjunction to standard chemotherapy has been shown to improve survival of this patient population. This prospective study was conducted to asse...

Introduction: The Phase III IMbrave150 study established atezolizumab + bevacizumab as standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis reports efficacy and safety results in patients with baseline Barcelona Clinic Liver Cancer (BCLC) Stage B disease. Methods: Patients with systemic treatment...

In Europe, the placement of hepatic artery ports in interventional radiology has facilitated the development of hepatic artery infusion (HAI) of chemotherapy. HAI of chemotherapy represents an effective option to downsize liver metastases from colorectal cancer, and enables curative intent hepatectomies in patients with previously unresectable live...

DNA mutations in cholangiocarcinoma: targeting IDH1 and other mutations Biliary tract cancers (BTC) are rare cancers with a poor prognosis, particularly at the metastatic stage, with a 5-year survival rate not exceeding 7%. Two lines of chemotherapy are currently recommended in France, with cisplatin-gemcitabine and 5 FU-oxaliplatin as first and se...

Introduction: Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC. Methods: The multi-r...

Background MODUL is an adaptable, signal-seeking trial designed to test novel agents in predefined patient subgroups in first-line metastatic colorectal cancer (mCRC). Patients and methods Patients with measurable, unresectable, previously untreated mCRC received induction with ≤8 cycles of FOLFOX + bevacizumab followed by randomization to mainten...

Cell migration is essential to living organisms and deregulated in cancer. Single cell’s migration ranges from traction-dependent mesenchymal motility to contractility-driven propulsive amoeboid locomotion, but collective cell migration has only been described as a focal adhesion–dependent and traction-dependent process. Here, we show that cancer c...

Immunotherapy has demonstrated its effectiveness in many cancers. In hepatocellular carcinoma (HCC), promising results shown in the first phase II studies evaluating anti-PD-1 or anti-PD-L1 monotherapies resulted in their approval in the United States. Approval was not obtained in Europe; subsequent randomized studies in first- or second-line treat...

Background Squamous cell anal carcinoma (SCAC) is an uncommon neoplasia often cured by surgery and/or chemo-adiation therapy at the localized stage. Although the first-line treatment for metastatic anal canal cancer is now better codified with two validated treatment regimens, carboplatin-paclitaxel and modified docetaxel-cisplatin-5FU (DCF), there...

Introduction: In the Phase 3 IMbrave150 trial (NCT03434379), atezolizumab + bevacizumab demonstrated a clinically meaningful survival benefit over sorafenib in patients with unresectable hepatocellular carcinoma (HCC), including those with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. We used IMbrave150 data to investigate the safet...

Background: Acute abdominal complications (AAC) in patients with deep neutropenia (DN) is challenging to manage because of the expected influence of AAC on oncological prognosis and higher surgical complication rate in a period of DN. In practice, these parameters are difficult to appreciate. This study reported our experience in managing these pa...

The metastatic progression of cancer remains a major issue in patient treatment. However, the molecular and cellular mechanisms underlying this process remain unclear. Here, we use primary explants and organoids from patients harboring mucinous colorectal carcinoma (MUC CRC), a poor-prognosis histological form of digestive cancer, to study the arch...

Background: The safety of bevacizumab in combination with chemotherapy in patients with inflammatory bowel disease (IBD) and digestive and nondigestive cancers is poorly documented. Methods: We retrospectively evaluated patient records of all adult cancer patients with IBD at our institution from April 2007 to May 2016 with an update in November...

Neuroendocrine carcinomas (NEC) are aggressive malignant diseases. Etoposide-based rechallenge (EBR) and the prognostic role of Rb status in second-line chemotherapy (2L) have not been studied. The objectives of this study were to report the results of 2L including EBR as well as prognostic factors in a national retrospective multicenter study. NEC...

4023 Background: Metastatic pancreatic cancer (mPC) remains a deadly disease with very limited treatment options. FFX is a standard first-line therapy for mPC with a median overall survival (mOS) of 11.1 months. CPI-613 is a stable intermediate of a lipoate analog that inhibits pyruvate dehydrogenase and α-ketoglutarate dehydrogenase enzymes of the...

L’accès aux tests génétiques dans le domaine de la cancérologie prend de plus en plus d’importance au fur et à mesure des découvertes de la recherche fondamentale, translationnelle et clinique. Il a ainsi été possible de démontrer que des cancers fréquents dont le diagnostic reposait essentiellement sur la localisation anatomique et l’examen anatom...

On May 1982, the US Food and Drug Administration (FDA) approved the use of streptozotocin to treat pancreatic neuroendocrine tumors (panNETs). Thus, this year marks forty years since that landmark date. This review of streptozotocin to treat panNETs is intended to commemorate this anniversary. A historical perspective of chemical structure, pharmac...

“Juvenile-like (hyperplastic/inflammatory) mucosal polyp” is a term proposed for rare benign mesenchymal lesions of the gastro-intestinal tract so far reported only in patients with type 1 neurofibromatosis (NF1). We report here a first sporadic case of NF1-associated mucosal inflammatory polyp of the colon. The diagnosis was made in a 53-year old...

470 Background: First-line atezolizumab (atezo) + bevacizumab (bev) has been approved in > 80 countries based on significantly longer survival vs sorafenib (sor) in systemic treatment (tx)–naive patients (pts) with unresectable HCC in IMbrave150 (NCT03434379; Finn NEJM 2020). This clinically meaningful tx benefit was maintained with an additional 1...

95 Background: Oxaliplatin, a major drug in metastatic colorectal cancer (MCRC), is responsible for a cumulative and limiting peripheral neuropathy (PN). Hepatic arterial infusion (HAI) chemotherapy, which makes sense in cases of exclusive or predominant liver metastases, increases the intratumor concentration of the administered drug(s) to improve...

605 Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of death by cancer worldwide. Mostly diagnosed with locally advanced or metastatic disease, patients lack for treatment options. Gene alterations (GAs) are frequently observed in PDAC, some of them considered as actionable with molecular targeted therapies (MTTs), wi...

Résumé Une fois sa spécialité choisie et selon son classement au concours, le nouvel interne en oncologie décide de la subdivision dans laquelle il souhaite se former parmi les 28 subdivisions existantes. Deux concernent des départements et territoires d’outre-mer : la subdivision Antilles-Guyane et la subdivision océan Indien. L’internat en oncolo...

Résumé L'accès aux tests génétiques dans le domaine de la cancérologie prend de plus en plus d'importance au fur et à mesure des découvertes de la recherche fondamentale, translationnelle et clinique. Il a ainsi été possible de démontrer que des cancers fréquents dont le diagnostic reposait essentiellement sur la localisation anatomique et l'examen...

Introduction In patients with unresectable liver metastases from colorectal cancer (CRCLM), systemic doublet or triplet chemotherapy and targeted therapy is considered a standard first-line treatment. Hepatic arterial infusion of oxaliplatin (HAI-ox) generates a high response rate, but this still needs to be confirmed in a randomized trial. We inco...