Thomas Filleron

• PhD, HDR
• Head Biostatistics & Health Data Science Unit at Institut Claudius Regaud

Previous results from CASSIOPEIA (NCT02541383) demonstrated superior progression-free survival (PFS) and minimal residual disease (MRD) negativity with the addition of daratumumab to bortezomib, thalidomide, and dexamethasone (VTd) induction/consolidation and with daratumumab maintenance versus observation in transplant-eligible newly diagnosed mul...

Resistance to immune checkpoint inhibitors (ICI) in cancer patients is not fully understood, and predictive biomarkers are lacking. MELANFα (NCT03348891) is an open‐label, prospective, multicenter cohort of 60 patients with advanced melanoma receiving ICI (bitherapy: ipilimumab + nivolumab; monotherapy: pembrolizumab or nivolumab). The primary obje...

Background Matching Adjusted Indirect Comparison (MAIC) is a statistical method used to adjust for potential biases when comparing treatment effects between separate data sources, with aggregate data in one arm, and individual patients data in the other. However, acceptance of MAIC in health technology assessment (HTA) is challenging because of the...

The reporting of adverse events (AEs) is fundamental to characterize safety profiles of novel therapeutic drug classes, however, conventional analysis strategies are suboptimal tools for this task. We therefore attempted to contribute to the modernization of AE analysis by encompassing the dimension of time, the duration and the recurrent nature of...

Background: Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), demonstrated superior efficacy over first-generation TKIs in the FLAURA trial, resulting in its approval as first-line therapy for metastatic non-small-cell lung cancer (NSCLC). However, the real-world application of these trial results requires an evaluation of seque...

Background Copy number alterations (CNA) are acquired during the evolution of cancers from their early stage to metastatic stage. This study aims at analysing the clinical value of the identified metastasis-associated CNAs both in metastatic breast cancers (mBCs) and early breast cancers (eBCs). Methods Single-nucleotide polymorphism (SNP)-array w...

Despite the widespread use of Cox regression for modeling treatment effects in clinical trials, in immunotherapy oncology trials and other settings therapeutic benefits are not immediately realized thereby violating the proportional hazards assumption. Weighted logrank tests and the so-called Maxcombo test involving the combination of multiple logr...

Purpose: The RAS/MEK signaling pathway is essential in carcinogenesis and frequently altered in non-small-cell lung cancer (NSCLC), notably by KRAS mutations (KRASm) that affect 25%-30% of non-squamous NSCLC. This study aims to explore the impact of KRASm subtypes on disease phenotype and survival outcomes. Patients and Methods: We conducted a re...

565 Background: SET2,3 index measures hormone receptor-related transcriptional activity (SET ER/PR ) adjusted for a baseline prognosis index (BPI) derived from tumor size, nodes involved and a 4-gene molecular subtype (RNA4). SET2,3 added prognostic information to the 21-gene Breast Recurrence Score (RS) in the SWOG 8814 trial (1). To confirm this,...

Background Breast cancer (BC) is the second most common cancer that metastasizes to the brain. Particularly up to half of patients with human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer (mBC) may develop brain metastases over the course of the disease. Nevertheless, little is known about the prevalence and th...

Background: The PEVOsq basket trial (NCT04357873) evaluated the efficacy of pembrolizumab and vorinostat (P+V) in patients (pts) with advanced squamous cell carcinoma (SCC) of different locationsAmong 112 pts included, 66 were HPV-positive (HPV+). Here we report HPV ctDNA monitoring in these pts. Methods: ctDNA before treatment (T0) and at first im...

Background: Epigenetic modulation plays a major role in escaping tumor immunosurveillance. PEVOsq (NCT04357873) was an open-label, non-randomized, multi-center, basket phase II trial evaluating the efficacy of pembrolizumab (P) and the vorinostat (V) HDAC inhibitor in 112 patients (pts) with recurrent and/or metastatic squamous cell carcinoma (SCC)...

Background Performance assessment of positron emission tomography (PET) scanners is crucial to guide clinical practice with efficiency. We have already introduced and experimentally evaluated a simulation method allowing the creation of a controlled ground truth for system performance assessment. In the current study, the goal was to validate the m...

Despite maximally safe resection of the magnetic resonance imaging (MRI)–defined contrast-enhanced (CE) central tumor area and chemoradiotherapy, most patients with glioblastoma (GBM) relapse within a year in peritumoral FLAIR regions. Magnetic resonance spectroscopy imaging (MRSI) can discriminate metabolic tumor areas with higher recurrence poten...

Background In case of locally advanced and/or non-metastatic unresectable esophageal cancer, definitive chemoradiotherapy (CRT) delivering 50 Gy in 25 daily fractions in combination with platinum-based regimen remains the standard of care resulting in a 2-year disease-free survival of 25% which deserves to be associated with new systemic strategies...

Even though male breast cancer (MBC) risk encompasses both genetic and environmental aetiologies, the primary risk factor is a germline pathogenic variant (PV) or likely pathogenic variant (LPV) in BRCA2, BRCA1 and/or PALB2 genes. To identify new potential MBC-specific predisposition genes, we sequenced a panel of 585 carcinogenesis genes in an MBC...

The mechanisms of action of and resistance to trastuzumab deruxtecan (T-DXd), an anti-HER2–drug conjugate for breast cancer treatment, remain unclear. The phase 2 DAISY trial evaluated the efficacy of T-DXd in patients with HER2-overexpressing (n = 72, cohort 1), HER2-low (n = 74, cohort 2) and HER2 non-expressing (n = 40, cohort 3) metastatic brea...

Purpose: Glioblastoma (GBM) systematically recurs after a standard 60 Gy radio-chemotherapy regimen. Since Magnetic Resonance Spectroscopic Imaging (MRSI) has been shown to predict the site of relapse, we analyzed the effect of MRSI-guided dose escalation on overall survival (OS) of patients with newly diagnosed GBM. Patients and methods: In thi...

Treatment of metastatic non-small cell lung cancer (mNSCLC) has been modified due to the development of immunotherapy. We assessed survival outcomes (overall [OS] and progression-free [rwPFS] survivals, time-to-next-treatment [TNT]) in mNSCLC patients after first-line immunotherapy and chemotherapy in real-life settings. Association between rwPFS a...

2597 Background: Epigenetic modulation plays a major role in escaping tumor immunosurveillance and confers resistance to immune checkpoint inhibitors. Preclinical evidence suggests that modulating the epigenome might improve the efficacy of immunotherapy. Patients and Methods: PEVOsq is an open-label, non-randomized, multi-center, basket phase II t...

Background: Lung cancer survivors are at high risk of developing a second primary cancer (SPC). We explored the Unicancer Epidemiology Strategy Medical-Economics for advanced or metastatic lung cancer (AMLC) database to assess the impact of immune checkpoint inhibitors (ICI) on the risk of SPC in patients with advanced/metastatic lung cancer. Pat...

Immunotherapy cancer clinical trials routinely feature an initial period during which the treatment is given without evident therapeutic benefit, which may be followed by a period during which an effective therapy reduces the hazard for event occurrence. The nature of this treatment effect is incompatible with the proportional hazards assumption, w...

Purpose: We aimed to determine the pattern of isolated local recurrences (ILR) in women with stage II-III hormone receptor-positive and human epidermal growth factor receptor 2 breast cancer (HR + /HER2-BC) after 10-year follow-up. Methods: UNICANCER-PACS 01 and PACS 04 trials included 5,008 women with T1-T3 and N1-N3 to evaluate the efficacy of...

Background Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the indivi...

Purpose: Several case reports and retrospective series have clearly pointed to the role of aprepitant, an antiemetic drug, in the development of encephalopathy when used with ifosfamide. Described as an inhibitor of several CYP metabolic pathways, aprepitant is suspected of drug-drug-interaction on ifosfamide pharmacokinetics. The pharmacokinetics...

Background: Small cell lung cancer (SCLC) is a highly aggressive entity of lung cancer with tendency toward early recurrence after first-line treatment. As per recently updated European Society for Medical Oncology recommendations, first-line treatment with up to 4 cycles of platinum-etoposide combined with immune checkpoint inhibitor (ICIs)-targe...

Background: The Keynote-045 trial illustrates that the long-term benefit (LTB) of treatment does not always translate to improved progression-free survival (PFS). Milestone survival and flexible parametric survival model with cure (FPCM) have been proposed as complementary statistical approaches to more comprehensively evaluate LTBs of treatments....

Background Positron emission tomography/computed tomography (PET/CT) fails to detect approximately 25% of aortic lymph node metastasis in patients with PET/CT stage IIIC1 cervical cancer. Surgical staging could lead to treatment modification and to improved para-aortic and distant control. Primary Objective(s) To demonstrate if chemoradiation with...

Background and purpose: To investigate the feasibility of using a multiapproach analysis combining clinical data, diffusion- and perfusion-weighted imaging, and 3D magnetic resonance spectroscopic imaging to distinguish true tumor progression (TP) from pseudoprogression (PSP) in patients with glioblastoma. Materials and methods: Progression was...

BACKGROUND. Glioblastoma (GB) gold standard treatment combines maximally-safe surgical resection of the contrast-enhanced (CE) central tumor area, as defined by MRI, and chemo-radiotherapy. However, most patients relapse within one year in non-CE peritumoral FLAIR regions. Spectroscopy MRI (MRSI) can discriminate metabolic tumor areas with higher r...

Introduction: There is a great need for data based on clinical trials for the older population in order to improve treatment. Historically, the inclusion rate of older adults in clinical trials has been low, but the rate specific to lung cancer is unknown, as are the factors associated with enrolment. Materials and methods: We used the national...

Background Neuropathic pain is common in cancer survivorship and is one of the most distressing symptoms for patients previously treated for head and neck cancer. Persistent neuropathic pain, when it is ongoing and uncontrolled, has a detrimental effect and erodes patients’ quality of life. Patients treated for head and neck cancer are chronic opio...

Contexte La « matching-adjusted indirect comparisons » (MAIC) est une méthode permettant de comparer les effets absolus des traitements lorsque la disponibilité des données individuelles des patients est limitée. Dans les études de vie réelle, la présence de données manquantes est un problème fréquent. L'imputation multiple (IM) est souvent utilisé...

Background Given the inherent challenges of conducting randomized phase III trials in older cancer patients, single-arm phase II trials which assess the feasibility of a treatment that has already been shown to be effective in a younger population may provide a compelling alternative. Such an approach would need to evaluate treatment feasibility ba...

Background: The efficacy and added benefit of platinum-based chemotherapy (PtCT) for metastatic breast cancer (MBC) remain unclear in patients with and without germline BRCA1 or BRCA2 mutations (gBRCA1/2m and gBRCA1/2wt, respectively). Methods: We selected from the French national real-world multicentre ESME cohort (2008-2016) all patients with...

The outcome of stage II–III colorectal cancer (CRC) is highly variable and therapeutic choice is currently based on TNM staging with a few additional biomarkers. However, studies show that some stage III patients have a better prognosis than some stage II patients. A promising consensus molecular (CMS) classification with prognostic relevance has b...

Trastuzumab deruxtecan (T-DXd) is an anti-HER2 (human epidermal growth factor receptor 2) antibody-drug conjugate which has previously shown efficacy in patients with HER2-overexpressing and HER2-low metastatic breast cancer (mBC). However, the mechanisms of action and resistance of this drug remain partially unclear. DAISY (NCT04132960) is a phase...

Cancer progression is driven in part by genomic alterations¹. The genomic characterization of cancers has shown interpatient heterogeneity regarding driver alterations², leading to the concept that generation of genomic profiling in patients with cancer could allow the selection of effective therapies3,4. Although DNA sequencing has been implemente...

Context: Matching-adjusted indirect comparison (MAIC) provides a method for comparing absolute treatment effects with limited availability of individual patient data (IPD). In real world studies, multiple imputations (MI) are often used to replace missing values with a set of plausible values that represent the uncertainty about the right value to...

Contexte : La « matching-adjusted indirect comparisons » (MAIC) est une méthode permettant de comparer les effets absolus des traitements lorsque la disponibilité des données individuelles des patients est limitée. Dans les études de vie réelle, la présence de données manquantes est un problème fréquent. L’imputation multiple (IM) est souvent utili...

Introduction L'arrivée de l'immunothérapie a marqué un tournant dans la prise en charge des cancers et a modifié le pronostic des patients traités pour un cancer de stade avancé ou métastatique dans plusieurs localisations. A partir d'un certain délai après le début du traitement, le terme « Bénéfice à long terme » est employé et il est envisagé qu...

Introduction Au cours de la dernière décennie, de nombreuses publications en oncologie ont évalué la valeur pronostique de biomarqueurs. Dans le cadre de biomarqueurs continus, il arrive fréquemment que celui-ci soit catégorisé, ce qui entraine une perte d'information (Altman, 2006). Pour permettre une évaluation pertinente, il est recommandé dans...

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Background: While studies have shown feasibility and reported preliminary evidence of utility, there is no evidence that multigene sequencing improves outcome in patients with metastatic cancer. The aim of the present study was to assess the clinical utility of multigene sequencing and DNA copy number analyses.. Methods: In SAFIR02-BREAST (NCT: 022...

Background: The HER2-targeted antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) demonstrated efficacy in heavily pretreated HER2-over- and HER2-low expressing ABC (1, 2). We aimed to assess the activity of T-DXd in HER2-over-, HER2-low and HER2-nul expressing ABC, to describe the drug mechanisms of action in the 3 cohorts and to identify...

PurposeTransoral robotic surgery (TORS) as a first-line therapy has been well-documented but evidence is missing regarding salvage therapy. The aim of this study is to compare the oncological and functional outcomes of TORS as a primary and salvage therapy.Methods This retrospective monocentric study included 74 patients operated by a single surgeo...

Introduction Les données de résultats cliniques en vie réelle avec le pembrolizumab en monothérapie chez des patients avec cancer bronchique non à petites cellules (CBNPC) avancé précédemment traités restent limitées. Notre objectif était d’estimer la survie globale (SG) et la survie sans progression en vie réelle (SSPvr) en France avec le pembroli...

Introduction Pembrolizumab a été le premier traitement anti-PD-1 autorisé en Europe dans le traitement de première ligne du cancer bronchique non à petites cellules métastatique (CBNPCm) non précédemment traité, à partir des résultats de l’étude KEYNOTE-024 démontrant une survie globale (SG) à 12 mois de 70,3 %. Notre objectif était d’estimer la SG...

Background: Genomic and immunologic tumor biomarker testing has dramatically changed the prognosis of patients, particularly those treated for advanced/metastatic non-squamous non-small-cell lung cancer (aNSCLC) when access to targeted agents is available. It remains unclear whether older patients have access to therapy-predictive biomarker testin...

Importance Compared with standard cytotoxic therapies, randomized immune checkpoint inhibitor (ICI) phase 3 trials reveal delayed benefits in terms of patient survival and/or long-term response. Such outcomes generally violate the assumption of proportional hazards, and the classical Cox proportional hazards regression model is therefore unsuitable...

Purpose Patients with locally advanced grade 2–3 extremity/truncal soft tissue sarcomas (STS) are at high risk of recurrence. The objective of this study was to assess the efficacy and feasibility of neoadjuvant concurrent chemoradiotherapy (cCRT) in selected grade 2–3 patients with limb or trunk wall STS, and to compare this schedule to a sequenti...

Introduction Malgré l’efficacité des anti-PD-1 et anti-CTLA-4 pour le traitement des mélanomes avancés, plus de 40 % des patients résistent ou rechutent dans les 5 ans suivant l’initiation du traitement et plus de 50 % des patients développent des effets indésirables inflammatoires de grade 3/4, dont des colites qui peuvent être traitées par anti-T...

Background Breast cancer may present genomic alterations leading to homologous recombination deficiency (HRD). PARP inhibitors have proven their efficacy in patients with HER2-negative (HER2-) metastatic breast cancer (mBC) harbouring germline (g) BRCA1/2 mutations in 3 phases III trials. The single-arm phase II RUBY trial included 42 patients, 40...

Background Cisplatin-based chemotherapy administered concurrently to thoracic radiation therapy is the recommended treatment for fit patients with unresectable stage III NSCLC. The aim of this study was to describe patient profiles and clinical outcomes for the different treatment strategies in a real-word setting. Methods The epidemio-strategy an...

Background In Europe, few data regarding the characteristics of EGFR exon 20 insertion (20ins) mutations in non-small cell lung cancer (NSCLC) are available.Objective Using a large real-world cohort, we assessed the incidence, characteristics, and outcomes of patients with non-squamous (nsq) NSCLC harboring EGFR exon 20ins.Patients and Methods The...

Purpose Observational studies using routinely collected data are faced with a number of potential shortcomings that can bias their results. Many methods rely on controlling for measured and unmeasured confounders. In this work, we investigate the use of instrumental variables (IV) and quasi-trial analysis to control for unmeasured confounders in th...

As illustrated in the setting of immune checkpoint inhibitors (ICI), a crucial goal in the development of new therapeutics is to propose a companion diagnostic test. This challenge is particularly complex with a continuous marker for which a threshold is needed. We analyzed data that have demonstrated that blood-based tumor mutational burden (bTMB)...

Introduction Metastatic non-small cell lung cancer is a disease with a poor prognosis and things may improve with the rise of immunotherapy. Clinical trials proved that immunotherapy had better results on survival than chemotherapy as first-line treatment for patients with metastatic lung cancer (MLC). Although clinical trials have strong internal...

Introduction Context: Metastatic lung cancer accounts for 40-50% of diagnosed lung cancers, and has a great lethality, with 4% 5-year net survival. Treatment has been recently modified due to the development of immunotherapy. In order to obtain faster results and to overcome the limitations associated with the use of overall survival (OS), the sear...

Introduction Plusieurs études récentes visant à démontrer l’efficacité d’un traitement utilisant le système immunitaire des patients pour lutter contre le cancer versus un traitement de référence, ont illustré les difficultés des méthodes classiques à mettre en évidence des différences réelles en termes de survie globale ou survie sans progression,...

Background The immune microenvironment (IME) of triple-negative breast cancers (TNBCs) and its modulation by neoadjuvant chemotherapy (NACT) remain to be fully characterized. Our current study aims to evaluate NACT-induced IME changes and assess the prognostic value of specific immune biomarkers. Methods Tumor-infiltrating lymphocytes (TILs) were...

Introduction Mini-invasive bronchoscopic techniques (such as radial endobronchial ultrasonography (rEBUS) and electromagnetic navigation (EMN)) have been developed to reach the peripheral lung but result in small samples. The feasibility of an adequate molecular testing from these specimens has been very little studied. Methods We retrospectively...

e16512 Background: Immune-checkpoint-inhibitors (ICI) provide durable antitumor activity even for recurrent and/or metastatic disease. As illustrated in the Keynote-045 study (pembrolizumab (pembro.) in second line metastatic urothelial carcinoma; Fradet, 2019), improvement in long-term responder fraction does not always translate into progression-...

TPS4588 Background: Consolidative local treatment of the primary tumor in the treatment of metastatic malignancies has shown promising results in several types of tumors, mostly relying on the seed-and-soil theory. Furthermore, the local treatment of the residual metastases following systemic treatment is a promising approach, in part due to the hi...

9062 Background: In Europe, 10-15% of non-squamous non-small cell lung cancer (nsqNSCLC) have EGFR mutations of which 5-12% are an Exon 20 insertion (20ins). Methods: Analysis of Epidemio-Strategy and Medical Economics (ESME) Advanced and Metastatic Lung cancer (AMLC) Data Platform (NCT03848052), a multicenter real-life database using a supervised,...

Squamous cell carcinomas (SCCs) are among the most frequent solid tumors in humans. SCCs, related or not to the human papillomavirus, share common molecular features. Immunotherapies, and specifically immune checkpoint inhibitors, have been shown to improve overall survival in multiple cancer types, including SCCs. However, only a minority of patie...

As key regulators of the actin cytoskeleton, RHO GTPase expression and/or activity are deregulated in tumorigenesis and metastatic progression. Nevertheless, the vast majority of experiments supporting this conclusion was conducted on cell lines but not on human tumor samples that were mostly studied at the expression level only. Up to now, the act...