Menée à l'aide de modèles murins, cette étude met en évidence un mécanisme par lequel une injection intratumorale de dinucléotiques cycliques activant la protéine STING augmente l'activité antitumorale des cellules NK et favorise l'élimination des tumeurs résistantes aux lymphocytes T CD8+

NK cells mediate clearance of CD8+ T cell–resistant tumors in response to STING agonists

Nicolai, Christopher J. ; Wolf, Natalie ; Chang, I. Chang ; Kirn, Georgia ; Marcus, Assaf ; Ndubaku, Chudi O. ; McWhirter, Sarah M. ; Raulet, David H.

Tumors with low neoantigen burden and/or diminished class I MHC expression evade CD8+ T cells, but NK cells provide another option to target such tumors for immune elimination. Nicolai et al. used several mouse models to investigate the mechanisms by which intratumoral injection of a cyclic dinucleotide (CDN) agonist for STING potentiated the antitumor activity of NK cells, both in the injected tumor and at a remote, uninjected tumor site. CDN administration induced type I interferons that [...]

Menée à l'aide de lignées cellulaires et d'un modèle murin, cette étude met en évidence un mécanisme par lequel les microparticules issues des cellules cancéreuses irradiées favorisent l'éradication de la tumeur en modifiant la polarité des macrophages du microenvironnement tumoral ainsi que les interactions de ces derniers avec les cellules cancéreuses

Irradiated tumor cell–derived microparticles mediate tumor eradication via cell killing and immune reprogramming

Wan, Chao ; Sun, Yajie ; Tian, Yu ; Lu, Lisen ; Dai, Xiaomeng ; Meng, Jingshu ; Huang, Jing ; He, Qianyuan ; Wu, Bian ; Zhang, Zhanjie ; Jiang, Ke ; Hu, Desheng ; Wu, Gang ; Lovell, Jonathan F. ; Jin, Honglin ; Yang, Kunyu

Radiotherapy (RT) is routinely used in cancer treatment, but expansion of its clinical indications remains challenging. The mechanism underlying the radiation-induced bystander effect (RIBE) is not understood and not therapeutically exploited. We suggest that the RIBE is predominantly mediated by irradiated tumor cell–released microparticles (RT-MPs), which induce broad antitumor effects and cause immunogenic death mainly through ferroptosis. Using a mouse model of malignant pleural effusion [...]

Menée à partir de données portant sur 385 patients atteints d'un carcinome hépatocellulaire traité entre 2006 et 2016, cette étude évalue l'effet d'une chimioembolisation artérielle sur les complications et la mortalité après une greffe hépatique

Liver transplantation outcomes after transarterial chemotherapy for hepatocellular carcinoma

Wallace, D. ; Cowling, T. E. ; Walker, K. ; Suddle, A. ; Gimson, A. ; Rowe, I. ; Callaghan, C. ; Sapisochin, G. ; Mehta, N. ; Heaton, N. ; van der Meulen, J.

Background : Transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) awaiting liver transplantation is widespread, although evidence that it improves outcomes is lacking and there exist concerns about morbidity. The impact of TACE on outcomes after transplantation was evaluated in this study. Methods : Patients with HCC who had liver transplantation in the UK were identified, and stratified according to whether they received TACE between 2006 and 2016. Cox [...]

Cet article passe en revue les différentes utilisations des impulsions électriques à haute tension dans le traitement des tumeurs solides (électroporation irréversible, électrochimiothérapie, électrotransfert de gènes, électrofusion et électro-immunothérapie)

High-Voltage Electrical Pulses in Oncology: Irreversible Electroporation, Electrochemotherapy, Gene Electrotransfer, Electrofusion, and Electroimmunotherapy

Geboers, Bart ; Scheffer, Hester J. ; Graybill, Philip M. ; Ruarus, Alette H. ; Nieuwenhuizen, Sanne ; Puijk, Robbert S. ; van den Tol, Petrousjka M. ; Davalos, Rafael V. ; Rubinsky, Boris ; de Gruijl, Tanja D. ; Miklavčič, Damijan ; Meijerink, Martijn R.

This review summarizes the use of high-voltage electrical pulses (HVEPs) in clinical oncology to treat solid tumors with irreversible electroporation (IRE) and electrochemotherapy (ECT). HVEPs increase the membrane permeability of cells, a phenomenon known as electroporation. Unlike alternative ablative therapies, electroporation does not affect the structural integrity of surrounding tissue, thereby enabling tumors in the vicinity of vital structures to be treated. IRE uses HVEPs to cause cell [...]

Menée à l'aide de modèles murins de cancer mammaire, cette étude démontre que les nanoparticules administrées par voie systémique interagissent avec les cellules immunitaires et peuvent, conjuguées ou non à un anticorps ciblant spécifiquement la tumeur, induire l'infiltration intratumorale des lymphocytes T CD8+ et la suppression des cellules cancéreuses

Nanoparticle interactions with immune cells dominate tumor retention and induce T cell–mediated tumor suppression in models of breast cancer

Korangath, Preethi ; Barnett, James D. ; Sharma, Anirudh ; Henderson, Elizabeth T. ; Stewart, Jacqueline ; Yu, Shu-Han ; Kandala, Sri Kamal ; Yang, Chun-Ting ; Caserto, Julia S. ; Hedayati, Mohammad ; Armstrong, Todd D. ; Jaffee, Elizabeth ; Gruettner, Cordula ; Zhou, Xian C. ; Fu, Wei ; Hu, Chen ; Sukumar, Saraswati ; Simons, Brian W. ; Ivkov, Robert

The factors that influence nanoparticle fate in vivo following systemic delivery remain an area of intense interest. Of particular interest is whether labeling with a cancer-specific antibody ligand (“active targeting”) is superior to its unlabeled counterpart (“passive targeting”). Using models of breast cancer in three immune variants of mice, we demonstrate that intratumor retention of antibody-labeled nanoparticles was determined by tumor-associated dendritic cells, neutrophils, monocytes, [...]

Menée in vitro et à l'aide de xénogreffes, cette étude identifie un mécanisme par lequel la limitation de l'apport en glucose dans les cellules cancéreuses exprimant fortement le transporteur de cystine/glutamate SLC7A11 provoque l'accumulation intracellulaire de cystine et de ponts disulfure, l'effondrement du système redox ainsi que la mort cellulaire, puis met en évidence un couplage entre le métabolisme de la cystine associé au transporteur SLC7A11 et la voie du pentose phosphate

Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer

Liu, Xiaoguang ; Olszewski, Kellen ; Zhang, Yilei ; Lim, Esther W. ; Shi, Jiejun ; Zhang, Xiaoshan ; Zhang, Jie ; Lee, Hyemin ; Koppula, Pranavi ; Lei, Guang ; Zhuang, Li ; You, M. James ; Fang, Bingliang ; Li, Wei ; Metallo, Christian M. ; Poyurovsky, Masha V. ; Gan, Boyi

SLC7A11-mediated cystine uptake is critical for maintaining redox balance and cell survival. Here we show that this comes at a significant cost for cancer cells with high levels of SLC7A11. Actively importing cystine is potentially toxic due to its low solubility, forcing cancer cells with high levels of SLC7A11 (SLC7A11high) to constitutively reduce cystine to the more soluble cysteine. This presents a significant drain on the cellular NADPH pool and renders such cells dependent on the pentose [...]

Menée à l'aide de modèles murins et d'échantillons de tissus pulmonaires sains ou cancéreux d'origine humaine, cette étude met en évidence un mécanisme de régulation qui altère les fonctions des cellules dendritiques conventionnelles de type 1 et réduit la réponse tumorale aux inhibiteurs de point de contrôle immunitaire

A conserved dendritic-cell regulatory program limits antitumour immunity

Maier, Barbara ; Leader, Andrew M. ; Chen, Steven T. ; Tung, Navpreet ; Chang, Christie ; LeBerichel, Jessica ; Chudnovskiy, Aleksey ; Maskey, Shrisha ; Walker, Laura ; Finnigan, John P. ; Kirkling, Margaret E. ; Reizis, Boris ; Ghosh, Sourav ; D’Amore, Natalie Roy ; Bhardwaj, Nina ; Rothlin, Carla V. ; Wolf, Andrea ; Flores, Raja ; Marron, Thomas ; Rahman, Adeeb H. ; Kenigsberg, Ephraim ; Brown, Brian D. ; Merad, Miriam

Checkpoint blockade therapies have improved cancer treatment, but such immunotherapy regimens fail in a large subset of patients. Conventional type 1 dendritic cells (DC1s) control the response to checkpoint blockade in preclinical models and are associated with better overall survival in patients with cancer, reflecting the specialized ability of these cells to prime the responses of CD8+ T cells1–3. Paradoxically, however, DC1s can be found in tumours that resist checkpoint blockade, [...]

Menée à l'aide de modèles murins d'adénocarcinome canalaire du pancréas, cette étude met en évidence l'intérêt d'induire la sénescence des cellules cancéreuses pour augmenter la vascularisation de la tumeur et améliorer la délivrance cellulaire ainsi que l'efficacité des anticancéreux

Senescence-Induced Vascular Remodeling Creates Therapeutic Vulnerabilities in Pancreas Cancer

Ruscetti, Marcus ; Morris, John P. I. V. ; Mezzadra, Riccardo ; Russell, James ; Leibold, Josef ; Romesser, Paul B. ; Simon, Janelle ; Kulick, Amanda ; Ho, Yu-Jui ; Fennell, Myles ; Li, Jinyang ; Norgard, Robert J. ; Wilkinson, John E. ; Alonso-Curbelo, Direna ; Sridharan, Ramya ; Heller, Daniel A. ; de Stanchina, Elisa ; Stanger, Ben Z. ; Sherr, Charles J. ; Lowe, Scott W.

KRAS mutant pancreatic ductal adenocarcinoma (PDAC) is characterized by a desmoplastic response that promotes hypovascularity, immunosuppression, and resistance to chemo- and immunotherapies. We show that a combination of MEK and CDK4/6 inhibitors that target KRAS-directed oncogenic signaling can suppress PDAC proliferation through induction of retinoblastoma (RB) protein-mediated senescence. In preclinical mouse models of PDAC, this senescence-inducing therapy produces a senescence-associated [...]

Menée à l'aide d'un modèle murin de gliome humain et de xénogreffes, cette étude met en évidence l'intérêt thérapeutique de nanoparticules de carbone dont la structure, maintenue par des groupes carboxyles et amines, permet d'imiter de grands acides aminés et de délivrer dans les cellules cancéreuses des médicaments via les transporteurs de type 1 (présents dans la plupart des tumeurs)

Targeted tumour theranostics in mice via carbon quantum dots structurally mimicking large amino acids

Li, Shuhua ; Su, Wen ; Wu, Hao ; Yuan, Ting ; Yuan, Chang ; Liu, Jun ; Deng, Gang ; Gao, Xingchun ; Chen, Zeming ; Bao, Youmei ; Yuan, Fanglong ; Zhou, Shixin ; Tan, Hongwei ; Li, Yunchao ; Li, Xiaohong ; Fan, Louzhen ; Zhu, Jia ; Chen, Ann T. ; Liu, Fuyao ; Zhou, Yu ; Li, Miao ; Zhai, Xingchen ; Zhou, Jiangbing

Strategies for selectively imaging and delivering drugs to tumours typically leverage differentially upregulated surface molecules on cancer cells. Here, we show that intravenously injected carbon quantum dots, functionalized with multiple paired α-carboxyl and amino groups that bind to the large neutral amino acid transporter 1 (which is expressed in most tumours), selectively accumulate in human tumour xenografts in mice and in an orthotopic mouse model of human glioma. The functionalized [...]

Mené sur 91 patients atteints d’un cancer de l’estomac ou de la jonction gastro-œsophagienne HER2+ de stade avancé, cet essai de phase II évalue l’efficacité, du point de vue de la survie sans progression, et la toxicité de l’ajout du trastuzumab au paclitaxel, après l’échec d’un traitement de première ligne combinant trastuzumab, fluoropyrimidine et sels de platine

Randomized, Phase II Study of Trastuzumab Beyond Progression in Patients With HER2-Positive Advanced Gastric or Gastroesophageal Junction Cancer: WJOG7112G (T-ACT Study)

Akitaka Makiyama, Yasutaka Sukawa, Tomomi Kashiwada (et al.)

PURPOSE : This study evaluated the continuous use of trastuzumab beyond progression (TBP) in human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer. PATIENTS AND METHODS : Patients with HER2-positive advanced G/GEJ cancer refractory to first-line chemotherapy with trastuzumab in combination with fluoropyrimidine and platinum were eligible. Patients were randomly assigned to the paclitaxel (80 mg/m2, days 1, 8, and 15, every 4 weeks) [...]

A partir d’une revue de la littérature publiée depuis 15 ans, cette étude analyse l’efficacité et la toxicité du bévacizumab pour traiter les patients atteints de divers types de cancers

Bevacizumab (Avastin) in cancer treatment: a review of 15 years of clinical experience and future outlook

Josep Garcia, Herbert I. Hurwitz, Alan B. Sandler (et al.)

When the VEGF-A-targeting monoclonal antibody bevacizumab (Avastin®) entered clinical practice more than 15 years ago, it was one of the first targeted therapies and the first approved angiogenesis inhibitor. Marking the beginning for a new line of anti-cancer treatments, it remains the most extensively characterized anti-angiogenetic treatment. Initially approved for treatment of metastatic colorectal cancer in combination with chemotherapy, indications of bevacizumab now include metastatic [...]

Mené sur 148 patients atteints d’une tumeur solide de stade avancé ou métastatique, cet essai de phase I évalue la dose maximale tolérée de l’anétumab ravtansine (un conjugué anticorps-médicament anti-mésothéline) et analyse ses caractéristiques pharmacocinétiques

First-in-Human, Multicenter, Phase I Dose-Escalation and Expansion Study of Anti-Mesothelin Antibody–Drug Conjugate Anetumab Ravtansine in Advanced or Metastatic Solid Tumors

Raffit Hassan, George R. Blumenschein Jr, Kathleen N. Moore (et al.)

PURPOSE : This phase I study, which to our knowledge is the first-in-human study of this kind, investigates the safety, tolerability, pharmacokinetics, and clinical activity of anetumab ravtansine, an antibody–drug conjugate of anti-mesothelin antibody linked to maytansinoid DM4, in patients with advanced, metastatic, or recurrent solid tumors known to express the tumor-differentiation antigen mesothelin. PATIENTS AND METHODS : This phase I, open-label, multicenter, dose-escalation and [...]

Mené sur 67 patients atteints d’une tumeur solide de stade avancé et sur 2 patients atteints d’un lymphome diffus à grandes cellules B réfractaire ou récidivant (âge médian : 57 ans), cet essai de phase I évalue la dose maximale tolérée d’un composé appelé CC-90010 (un inhibiteur de BET dispensé par voie orale) et analyse ses caractéristiques pharmacocinétiques et pharmacodynamiques après l’échec de plusieurs lignes de traitements (nombre médian de thérapies antérieures : 4)

Phase I study of CC-90010, a reversible, oral BET inhibitor in patients with advanced solid tumors and relapsed/refractory non-Hodgkin lymphoma

V.Moreno, M.Sepulveda, M.Vieito (et al.)

Background : Bromodomain and extra-terminal (BET) proteins are epigenetic readers that regulate expression of genes involved in oncogenesis. CC-90010 is a novel, oral, reversible, small-molecule BET inhibitor. Patients and methods : CC-90010-ST-001 (NCT03220347; 2015-004371-79) is a phase I dose-escalation and expansion study of CC-90010 in patients with advanced or unresectable solid tumors and relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). We report results from the dose escalation [...]

Mené sur 211 patients atteints d’une leucémie myéloïde aiguë et inéligibles à une chimiothérapie intensive (âge médian : 76 ans), cet essai de phase III évalue l’efficacité, du point de vue de la survie globale, et la toxicité de l’ajout du vénétoclax à de faibles doses de cytarabine

Venetoclax plus LDAC for patients with untreated AML ineligible for intensive chemotherapy: phase 3 randomized placebo-controlled trial

Andrew Henry Wei , Pau Montesinos , Vladimir Ivanov (et al.)

Background: Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. Methods: Adults ?18 years with newly diagnosed AML ineligible for intensive chemotherapy were enrolled in this international Phase 3 randomized, double-blind, placebo-controlled trial. Patients (N=211) were randomized 2:1 to either: venetoclax (N=143) or placebo (N=68) in 28-day cycles, plus low-dose cytarabine (LDAC) on days 1-10. The primary endpoint [...]

Mené sur 23 enfants atteints d’une leucémie lymphoblastique aiguë à cellules B réfractaire ou récidivante (âge médian : 12 ans), cet essai évalue l’efficacité, du point de vue du taux de réponse, et la toxicité de la décitabine et du vorinostat en combinaison avec une chimiothérapie (vincristine, dexaméthasone, mitoxantrone et PEG-asparaginase) et analyse les caractéristiques pharmacodynamiques de cette combinaison

Decitabine and Vorinostat with Chemotherapy in Relapsed Pediatric Acute Lymphoblastic Leukemia: A TACL Pilot Study

Michael J. Burke, Rumen Kostadinov, Richard Sposto (et al.)

Purpose: Treatment failure from drug resistance is the primary reason for relapse in acute lymphoblastic leukemia (ALL). Improving outcomes by targeting mechanisms of drug resistance is a potential solution. Patients and Methods: We report results investigating the epigenetic modulators decitabine and vorinostat with vincristine, dexamethasone, mitoxantrone, and PEG-asparaginase for pediatric patients with relapsed or refractory B-cell ALL (B-ALL). Twenty-three patients, median age 12 years [...]

A partir d’une revue systématique de la littérature publiée entre 2010 et 2019 (9 essais, 5 051 patients), cette méta-analyse évalue la toxicité, du point de vue de la survenue d’événements indésirables de nature immunitaire, des inhibiteurs de points de contrôle immunitaire chez des patients atteints d’un mélanome de stade avancé

Immune Checkpoint Inhibitors and Immune-Related Adverse Events in Patients With Advanced Melanoma: A Systematic Review and Network Meta-analysis

Ching-Yuan Chang, Haesuk Park, Daniel C. Malone (et al)

Importance : Since 2011, immune checkpoint inhibitors (ICIs) have been effective treatment options for advanced melanoma. Little is known about how risks of immune-related adverse events (irAEs) vary by ICIs. Objective To compare the risk of irAEs across different treatment regimens for advanced melanoma using network meta-analysis. Data Sources PubMed/MEDLINE, Embase, Web of Science, and Scopus were searched for all randomized clinical trial (RCT) articles published from January 1, 2010, [...]

Cette étude passe en revue les essais évaluant l’efficacité des immunothérapies chez des patients atteints d’un cancer du pancréas

Immunotherapy for pancreatic cancer: A 2020 update

Dimitrios Schizas, Nikolaos Charalampakis, Christo Kole (et al.)

Pancreatic adenocarcinoma (PAC) is associated with extremely poor prognosis and remains a lethal malignancy. The main cure for PAC is surgical resection. Further treatment modalities, such as surgery, chemotherapy, radiotherapy and other locoregional therapies provide low survival rates. Currently, many clinical trials seek to assess the efficacy of immunotherapeutic strategies in PAC, including immune checkpoint inhibitors, cancer vaccines, adoptive cell transfer , combinations with other [...]

Mené sur 190 patients atteints d’un cancer du poumon non à petites cellules de stade IV, cet essai de phase II évalue l’efficacité, du point de vue de la survie globale, et la toxicité de Vx-001, un vaccin thérapeutique ciblant TERT, dispensé en traitement d’entretien après une chimiothérapie de première ligne à base de sels de platine

Clinical activity of a htert (vx-001) cancer vaccine as post-chemotherapy maintenance immunotherapy in patients with stage IV non-small cell lung cancer: final results of a randomised phase 2 clinical trial

Gridelli, C., Ciuleanu, T., Domine, M. (et al.)

Background : The cancer vaccine Vx-001, which targets the universal tumour antigen TElomerase Reverse Transcriptase (TERT), can mount specific Vx-001/TERT572 CD8?+?cytotoxic T cells; this immune response is associated with improved overall survival (OS) in patients with advanced/metastatic non-small cell lung cancer (NSCLC). Methods : A randomised, double blind, phase 2b trial, in HLA-A*201-positive patients with metastatic, TERT-expressing NSCLC, who did not progress after first-line [...]

Menée par enquête auprès de 13 oncologues européens, cette étude analyse les facteurs associés à leur prise de décision concernant le traitement de deuxième ligne chez des patients atteints d’un cancer du poumon à petites cellules de stade IV

Choice of second-line systemic therapy in stage IV small cell lung cancer (SCLC) – a survey amongst European lung cancer experts

M Früha, CM Panjec, M Reckd (et al.)

Objectives : Stage IV small cell lung cancer (SCLC) is associated with short survival and progression after first-line systemic therapy frequently occurs within months. Although topotecan is approved for second-line treatment, its efficacy is limited, and treatment heterogeneity exists. Material and Methods : The decision-making patterns for second line treatment of 13 European medical oncologists with expertise in SCLC were analyzed. Results : The two criteria most relevant to decision making [...]

Mené sur 21 patients atteints d’un chondrosarcome de stade avancé présentant des mutations du gène IDH1 (âge médian : 55 ans), cet essai de phase I évalue la dose maximale tolérée et l’efficacité, du point de vue de la survie sans progression, de l’ivosidénib, un inhibiteur de l'IDH dispensé en monothérapie

Phase I Study of the Mutant IDH1 Inhibitor Ivosidenib: Safety and Clinical Activity in Patients With Advanced Chondrosarcoma

William D. Tap, Victor M. Villalobos, Gregory M. Cote (et al.)

PURPOSE : Surgery is the primary therapy for localized chondrosarcoma; for locally advanced and/or metastatic disease, no known effective systemic therapy exists. Mutations in the isocitrate dehydrogenase 1/2 (IDH1/2) enzymes occur in up to 65% of chondrosarcomas, resulting in accumulation of the oncometabolite D-2-hydroxyglutarate (2-HG). Ivosidenib (AG-120) is a selective inhibitor of mutant IDH1 approved in the United States for specific cases of acute myeloid leukemia. We report outcomes of [...]

Mené en Italie sur 1 214 patientes atteintes d’un cancer du sein de stade précoce à haut risque de récidive, cet essai de phase III évalue l’efficacité, du point de vue de la survie globale et de la survie sans progression, d’une chimiothérapie adjuvante à doses intensifiées de fluorouracile, épirubicine et cyclophosphamide (durée médiane de suivi : 15,8 ans)

Dose-dense adjuvant chemotherapy in early breast cancer patients: 15-year results of the Phase 3 Mammella InterGruppo (MIG)-1 study

Eva Blondeaux, Matteo Lambertini, Andrea Michelotti (et al.)

Background : Adjuvant chemotherapy is the standard of care in high-risk early breast cancer patients. Dose-dense should be the preferred schedule of administration. However, its long-term benefit is unknown. Methods : In the Italian multicentre Phase 3 randomised MIG-1 trial, node-positive and high-risk node- negative breast cancer patients were randomised to receive six cycles of adjuvant fluorouracil, epirubicin and cyclophosphamide regimen administered every 3 (FEC21) or 2 (FEC14) weeks. The [...]

Cette étude analyse les données de l'essai clinique ayant conduit la "Food and Drug Administration" à autoriser l'utilisation de l’ado-trastuzumab emtansine en traitement adjuvant chez des patientes atteintes d’un cancer du sein de stade précoce HER2+

FDA Approval Summary: Ado-trastuzumab emtansine for the adjuvant treatment of HER2-positive early breast cancer

Suparna Wedam, Lola Fashoyin-Aje, Xin Gao (et al.)

On May 3, 2019, the FDA granted regular approval to ado-trastuzumab emtansine (KADCYLA), for the adjuvant treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC) who have residual invasive disease after neoadjuvant taxane based chemotherapy and trastuzumab-based treatment. Approval was based on data from the KATHERINE trial, which randomized patients to receive ado-trastuzumab emtansine or trastuzumab. At three years, the event free rate for [...]

A partir d'une revue systématique de la littérature (91 études), cette étude analyse la qualité des études évaluant la possibilité d'utiliser en cancérologie la survie sans progression comme critère de jugement à la place de la survie globale

Progression-free survival as a surrogate for overall survival in oncology trials: a methodological systematic review

Belin, Lisa ; Tan, Aidan ; De Rycke, Yann ; Dechartres, Agnes

Background : Progression-free survival (PFS) is a surrogate endpoint widely used for overall survival (OS) in oncology. Validation of PFS as a surrogate must be done for each indication and each intervention. We aimed to identify all studies evaluating the validity of PFS as a surrogate for OS in oncology, and to describe their methodological characteristics. Methods : We conducted a systematic review by searching MEDLINE via PubMed and the Cochrane Library with no limitation on time, selected [...]

A partir d'une revue systématique de la littérature (80 articles), cette étude identifie les politiques visant à réduire les prix des médicaments à leur lancement sur le marché et analyse les données quantitatives sur lesquelles sont fondées ces politiques

Evidence Underlying Policy Proposals for Sustainable Anticancer Drug Prices: A Systematic Review

Franzen, Nora ; Retèl, Valesca P. ; Schats, Winnie ; van Harten, Wim H.

The financial consequences of high-expenditure innovative drugs and the association of these consequences with access to cancer treatment are substantial. With oncology being one of the major spending blocks of care and research, innovative policies are needed to secure the sustainability and accessibility of health care systems. Despite this strong interest, structured approaches are missing to date, and proposals are often based on opinion rather than fact.To evaluate an inventory of policies [...]

Cet article passe en revue les études récentes évaluant l'intérêt de modifier les habitudes alimentaires pour améliorer l'efficacité des traitements anticancéreux

Dietary modifications for enhanced cancer therapy

Kanarek, Naama ; Petrova, Boryana ; Sabatini, David M.

Tumours depend on nutrients supplied by the host for their growth and survival. Modifications to the host’s diet can change nutrient availability in the tumour microenvironment, which might represent a promising strategy for inhibiting tumour growth. Dietary modifications can limit tumour-specific nutritional requirements, alter certain nutrients that target the metabolic vulnerabilities of the tumour, or enhance the cytotoxicity of anti-cancer drugs. Recent reports have suggested that [...]

Cet article présente les recommandations de l'"ASCO" concernant le traitement par voie systémique d'un mélanome

Systemic Therapy for Melanoma: ASCO Guideline

Seth, Rahul ; Messersmith, Hans ; Kaur, Varinder ; Kirkwood, John M. ; Kudchadkar, Ragini ; McQuade, Jennifer Leigh ; Provenzano, Anthony ; Swami, Umang ; Weber, Jeffrey ; Alluri, Krishna C. ; Agarwala, Sanjiv ; Ascierto, Paolo A. ; Atkins, Michael B. ; Davis, Nancy ; Ernstoff, Marc S. ; Faries, Mark B. ; Gold, Jason S. ; Guild, Samantha ; Gyorki, David E. ; Khushalani, Nikhil I. ; Meyers, Michael O. ; Robert, Caroline ; Santinami, Mario ; Sehdev, Amikar ; Sondak, Vernon K. ; Spurrier, Gilliosa ; Tsai, Katy K. ; van Akkooi, Alexander ; Funchain, Pauline

PURPOSE : To provide guidance to clinicians regarding the use of systemic therapy for melanoma. METHODS : ASCO convened an Expert Panel and conducted a systematic review of the literature. RESULTS : A systematic review, one meta-analysis, and 34 additional randomized trials were identified. The published studies included a wide range of systemic therapies in cutaneous and noncutaneous melanoma. RECOMMENDATIONS : In the adjuvant setting, nivolumab or pembrolizumab should be offered to patients [...]

Dans le cadre de la préparation d'une réunion de planification d'essais cliniques organisée en octobre 2018 par le "National Institute of Cancer", cet article résume les données des études pré-cliniques et cliniques concernant les régulateurs des processus de réparation des dommages causés à l'ADN afin d'identifier de nouvelles stratégies pour traiter les cancers du col de l'utérus

Moving Forward in Cervical Cancer - Enhancing Susceptibility to DNA Repair Inhibition and Damage: NCI Clinical Trials Planning Meeting Report

Harkenrider, Matthew M. ; Markham, Merry Jennifer ; Dizon, Don S. ; Jhingran, Anuja ; Salani, Ritu ; Serour, Ramy K. ; Lynn, Jean ; Kohn, Elise C.

Cervical cancer is the fourth most common cancer in women worldwide, and prognosis is poor for those who experience recurrence or develop metastatic disease, in part due to the lack of active therapeutic directions. The National Cancer Institute convened a Cervical Cancer Clinical Trials Planning Meeting (CTPM) in October 2018 to facilitate the design of hypothesis-driven clinical trials focusing on locally advanced, metastatic and recurrent cervical cancer around the theme of enhancing [...]