Second-line targeted therapies after nivolumab-ipilimumab failure in metastatic renal cell carcinoma

Correction: Volume: 119 Pages: 200-201 DOI: 10.1016/j.ejca.2019.04.012 Published: SEP 2019Background: Nivolumab-ipilimumab demonstrated a survival benefit over sunitinib in first-line setting for metastatic renal cell carcinomas (mRCCs) and is becoming a new standard of care for naive patients with intermediate or poor risk prognosis (International mRCC Database Consortium). The efficacy of subsequent vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs) after nivolumab-ipilimumab failure remains unclear. Methods: Medical records of mRCC patients treated with nivolumab-ipilimumab, who received subsequent TKI, as part of Checkmate 214 study were reviewed in 13 institutions. Baseline characteristics, outcome data including progression-free survival (PFS), response, overall survival (OS) and toxicities were retrospectively collected. Results: Overall 33 patients received subsequent TKI after nivolumab-ipilimumab failure. Median follow-up from start of subsequent TKI is 22 months (19-NR). Best response was assessed in 30 patients: 12 partial responses (36%), 13 stable diseases (39%) and five progressive diseases (15%). Median PFS from start of TKI was 8 months [5-13]. Median PFS with first-generation (sunitinib/pazopanib) and second-generation TKI (axitinib/cabozantinib) was 8 months [5-16] and 7 months (5-NA), respectively. PFS in second line was significantly longer in patients with a long first-line duration of response to the double immune checkpoint blockade (>= 6 months) with 8 versus 5 months for short responder (= 3. Conclusion: This is the first report of outcomes with TKI, after first-line nivolumab-ipilimumab failure. Median PFS suggests a sustained benefit of TKI and supports trials investigating the optimal sequence. (C) 2018 Published by Elsevier Ltd.Peer reviewe

From the methodologist to the clinician : health-related quality of life as an instrument for the patient-centered oncology care ?

Les mesures de santé perçue par le patient ou patient-reported outcome (PRO) sont définies comme tout rapport sur l’état de santé du patient provenant directement du patient, sans interprétation de la réponse du patient par un clinicien ou toute autre personne. La qualité de vie relative à la santé (QdV) fait partie de la famille des PRO. L’intérêt des données de PRO et de QdV en recherche clinique est reconnu, notamment comme critère de jugement secondaire dans les essais cliniques de phase III randomisés. Il persiste toutefois à encore améliorer le niveau de preuves pour qu’elles deviennent un élément incontournable des prises de décisions tant cliniques qu’en politique de santé. De plus l’intégration de leur mesure au cours de la pratique quotidienne pourrait permettre d’améliorer la prise en charge globale des patientsCes constatations nous ont conduit à mettre en place plusieurs études destinées à légitimer l’utilisation des données de PRO et de QdV comme aide à la décision. Nous distinguerons deux cadres : celui de la recherche clinique et la pratique de routine.En recherche clinique, nous présenterons successivement les deux études suivantes :- l’évaluation de la concordance des résultats de PRO et des critères de jugement « classiques » en fonction de la conception en ouvert ou aveugle des études incluant des patients atteints d’un cancer de prostate au travers d’une revue systématique de la littérature,- l’étude SURF qui va évaluer de manière prospective la QdV des patients atteints d’un cancer du rein et traités par Sunitinib avec un schéma d’administration expérimentalEn pratique de routine, nos travaux ont porté sur :- l’utilisation en routine de la QdV pour aider à l’évaluation globale du patient et optimiser les soins centrés sur le patient au travers des études QOLIBRY et QUANARIE,- l’analyse de la satisfaction des médecins vis à vis de l’utilisation en routine des données de QdV aux cours des études QUANARIE et QOLIBRY.Patient-reported outcome (PRO) are defined as any report on the patient's state of health that comes directly from the patient, without interpretation of the patient's response by a clinician or any other person. Health-related quality of life (HRQoL) is part of the PRO. The value of PRO and HRQoL data in clinical research is well established, particularly as a secondary endpoint in randomized phase III trials. However, there is still a need to further improve the level of evidence so that it becomes an essential element in both clinical and health policy decision-making. In addition, the integration of their measurement into daily practice could improve the overall management of patients.These findings led us to set up several studies to legitimize the use of PRO and QoL data as a decision-making tool. We will distinguish two frameworks: that of clinical research and routine practice.In clinical research, we will successively present the following two studies:- the evaluation of the concordance of PRO results with "classical" outcome based on the open or blind design of studies with prostate cancer patients through a systematic review of the literature,- the SURF study, which will prospectively assess renal cancer patients’ HRQoL treated with Sunitinib and an experimental administration regimenIn routine practice, our work focused on:- the routine use of QoL to assist in the assessment of the patient and optimize patient-centered care through the QOLIBRY and QUANARIE feasibility studies,- the analysis of physician satisfaction with the routine use of QoL data in the QUANARIE and QOLIBRY studies

Experimental test of a micro-mirror array as an adaptive apodizer for high-contrast imaging

International audienceDirect imaging systems are now designed for specific telescope apertures and specific high-contrast diffraction 2D patterns. Current coronagraphic masks are not adaptive components, and different apertures and science requirements must result in different masks, which always come in a small number in a real-life instrument. Adaptive components would make it possible to adapt to changes in the aperture transmission (which will likely happen on a daily basis with the near future highly segmented telescopes, such as ESO's ELT), as well as to reconfigure at will the high-contrast area for different observation modes. In particular, the prospect of characterizing planets with a known position at a high spectral resolution pushes for adaptive coronagraphs capable of creating high-contrast in a small area of the image plane. Micro-mirror arrays are commercially available MOEMS that may be used as binary adaptive amplitude mask. They adaptively redirect light in either one of two directions using millions of micron-sized, bi-stable mirrors. Their spatial resolutions is compatible with 2D binary apodization patterns, in addition to Lyot stops. We have conducted a series of laboratory tests to assess the compatibility of an off-the-shelf micro-mirror array with high-contrast imaging requirements. This communication first presents the context and the scope of the project. It then details the results of our initial characterization of the device, in particular a measurement of the wavefront aberrations and of the level of scattered light that it introduces. Finally, it presents high-contrast point-spread functions obtained with this device, and summarizes the limitations of current components to derive a possible roadmap for the development of scientific-grade adaptive pupil masks

Pathologic Complete Response to Preoperative Chemotherapy Predicts Cure in Early-Stage Non-Small-Cell Lung Cancer: Combined Analysis of Two IFCT Randomized Trials.

International audienceINTRODUCTION:: Our study aimed to evaluate whether pathologic complete response (pCR) in early-stage non-small-cell lung cancer (NSCLC) after neoadjuvant chemotherapy resulted in improved outcome, and to determine predictive factors for pCR. METHODS:: Eligible patients with stage-IB or -II NSCLC were included in two consecutive Intergroupe Francophone de Cancérologie Thoracique phase-III trials evaluating platinum-based neoadjuvant chemotherapy, with pCR defined by the absence of viable cancer cells in the resected surgical specimen. RESULTS:: Among the 492 patients analyzed, 41 (8.3%) achieved pCR. In the pCR group, 5-year overall survival was 80.0% compared with 55.8% in the non-pCR group (p = 0.0007). In multivariate analyses, pCR was a favorable prognostic factor of overall survival (relative risk = 0.34; 95% confidence interval = 0.18-0.64) in addition to squamous-cell carcinoma, weight loss less than or equal to 5%, and stage-IB disease. Five-year disease-free survival was 80.1% in the pCR group compared to 44.8% in the non-pCR group (p < 0.0001). Two patients (4.9%) in the pCR group experienced disease recurrence compared to 193 patients (42.8%) in the non-pCR group. SCC subtype was the only independent predictor of pCR (odds ratio [OR] = 4.30; 95% confidence interval = 1.90-9.72). CONCLUSION:: Our results showed that pCR after preoperative chemotherapy was a favorable prognostic factor in stage-IB-II NSCLC. Our study is the largest published series evaluating pCRs after preoperative chemotherapy. The only factor predictive of pCR was squamous-cell carcinoma. Identifying molecular predictive markers for pCR may help in distinguishing patients likely to benefit from neoadjuvant chemotherapy and in choosing the most adequate preoperative chemotherapy regimen

Surveillance des patients atteints de tumeur germinale du testicule

International audienc

Health-related quality of life assessment for patients with advanced or metastatic renal cell carcinoma treated with a tyrosine kinase inhibitor using electronic patient-reported outcomes in daily clinical practice (QUANARIE trial): study protocol

Abstract Background Two main therapies, pazopanib and sunitinib, are used in the first-line setting for metastatic renal cell carcinoma (mRCC). These two tyrosine kinase inhibitors (TKI) are equally effective in terms of survival; however, they frequently induce adverse events. In this setting, Health-Related Quality of life (HRQoL) is a key element in the choice between these two treatments and the evaluation of treatment effectiveness. It could be of interest to evaluate HRQoL in daily clinical practice to aid adequate therapy choice and management. Currently, the development of information and communication technology may allow HRQoL monitoring in routine practice. The objective of the QUANARIE study is to evaluate the use of HRQoL assessment in daily clinical practice for patients with mRCC treated with TKI using electronic patient-reported outcomes (e-PRO). The present article describes the key elements of the study protocol. Methods The QUANARIE study is an interventional, prospective, multicentre trial. Patients diagnosed with mRCC initiating sunitinib or pazopanib treatment will be invited to complete the EORTC QLQ-C30 questionnaire, nine additional questions from the EORTC items library, and the EuroQoL EQ-5D, prior to each visit with the physician. Questionnaires will be completed by patients using tablets and/or computer terminals via the e-PRO software. The physician will have real-time access to a visual summary of the HRQoL evaluation. The primary objective is to assess the proportion of patients having good compliance with Routine Electronic Monitoring of HRQoL (REMOQOL) during the first 12 months. Physicians’ satisfaction with REMOQOL will be assessed as a secondary objective. We hypothesise that 80% of patients having good compliance with REMOQOL would be meaningful. A sample size of 56 patients would be needed. Discussion The results of this study will show whether REMOQOL is feasible on a large scale and whether patients are receptive to this new practice. This study will also determine how real-time multidimensional evaluation of patient perception can help physicians in their daily practice and how they used it in conjunction with other clinical information to manage patient care. Trial registration ClinicalTrials.gov; Identifier: NCT03062410; First Posted: February 23, 2017; Last Update Posted: August 9, 2017

A novel Chr1-miR-200 driven whole transcriptome signature shapes tumor immune microenvironment and predicts relapse in early-stage lung adenocarcinoma

Abstract Background In Lung adenocarcinoma (LUAD), targeted therapies and immunotherapies have moved from metastatic to early stage and stratification of the relapse risk becomes mandatory. Here we identified a miR-200 based RNA signature that delineates Epithelial-to-mesenchymal transition (EMT) heterogeneity and predicts survival beyond current classification systems. Methods A miR-200 signature was identified using RNA sequencing. We scored the miR-200 signature by WISP (Weighted In Silico Pathology), used GSEA to identify pathway enrichments and MCP-counter to characterize immune cell infiltrates. We evaluate the clinical value of this signature in our series of LUAD and using TCGA and 7 published datasets. Results We identified 3 clusters based on supervised classification: I is miR-200-sign-down and enriched in TP53 mutations IIA and IIB are miR-200-sign-up: IIA is enriched in EGFR (p < 0.001), IIB is enriched in KRAS mutation (p < 0.001). WISP stratified patients into miR-200-sign-down (n = 65) and miR-200-sign-up (n = 42). Several biological processes were enriched in MiR-200-sign-down tumors, focal adhesion, actin cytoskeleton, cytokine/receptor interaction, TP53 signaling and cell cycle pathways. Fibroblast, immune cell infiltration and PDL1 expression were also significantly higher suggesting immune exhaustion. This signature stratified patients into high-vs low-risk groups, miR-200-sign-up had higher DFS, median not reached at 60 vs 41 months and within subpopulations with stage I, IA, IB, or II. Results were validated on TCGA data on 7 public datasets. Conclusion This EMT and miR-200-related prognostic signature refines prognosis evaluation independently of tumor stage and paves the way towards assessing the predictive value of this LUAD clustering to optimize perioperative treatment