Mené sur 104 patients atteints d'un cancer de la prostate de stade cT2-3 ne présentant pas d'envahissement ganglionnaire à la résection (durée médiane de suivi : 14 ans), cet essai évalue, du point de vue de la survie spécifique et de la survie globale à long terme, l'intérêt d'ajouter à une radiothérapie externe une curiethérapie par implant d'iridium

Long-Term Results of a Randomized Trial Comparing Iridium Implant Plus External-Beam Radiation Therapy with External-Beam Radiation Therapy Alone in Node-Negative Locally Advanced Cancer of the Prostate

Dayes, I. S. ; Parpia, S. ; Gilbert, J. ; Julian, J. A. ; Davis, I. R. ; Levine, M. N. ; Sathya, J.

Purpose : To determine the impact on long-term survival from the addition of brachytherapy to external beam radiation therapy (EBRT) in patients with prostate cancer. Materials and Methods : Between 1992 and 1997, 104 men with cT2-3, surgically staged node-negative prostate cancer were randomized to receive either EBRT (40Gy/20 fractions) with iridium implant (35Gy/48 h) or EBRT alone (66Gy/33 fractions) to the prostate. Based on T- stage, Gleason score and PSA (Prostate-Specific Antigen), 60% [...]

Menée in vitro et à l'aide de modèles murins, cette étude met en évidence une association entre le niveau d'expression de PD-1 sur les macrophages spécifiques de la tumeur et l'inhibition du processus de phagocytose et de l'immunité tumorale

PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity

Gordon, Sydney R. ; Maute, Roy L. ; Dulken, Ben W. ; Hutter, Gregor ; George, Benson M. ; McCracken, Melissa N. ; Gupta, Rohit ; Tsai, Jonathan M. ; Sinha, Rahul ; Corey, Daniel ; Ring, Aaron M. ; Connolly, Andrew J. ; Weissman, Irving L.

Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor that is upregulated on activated T cells for the induction of immune tolerance1, 2. Tumour cells frequently overexpress the ligand for PD-1, programmed cell death ligand 1 (PD-L1), facilitating their escape from the immune system3, 4. Monoclonal antibodies that block the interaction between PD-1 and PD-L1, by binding to either the ligand or receptor, have shown notable clinical efficacy in patients with a variety of [...]

Menée à l'aide d'un modèle murin de cancer de la prostate de stade avancé, cette étude met en évidence l'intérêt d'une nanoformulation d'olaparib pour augmenter l'inhibition de l'enzyme PARP et sensibiliser aux rayonnements ionisants les cellules tumorales n'exprimant pas les protéines PTEN et TP53

Nanoformulation of Olaparib amplifies PARP inhibition and sensitizes PTEN/TP53-deficient prostate cancer to radiation

van de Ven, Anne L. ; Tangutoori, Shifalika ; Baldwin, Paige ; Qiao, Ju ; Gharagouzloo, Codi ; Seitzer, Nina ; Clohessy, John G. ; Makrigiorgos, G. Mike ; Cormack, Robert ; Pandolfi, Pier Paolo ; Sridhar, Srinivas

The use of PARP inhibitors in combination with radiation therapy is a promising strategy to locally enhance DNA-damage in tumors. Here we show that radiation-resistant cells and tumors derived from a Pten/Trp53-deficient mouse model of advanced prostate cancer are rendered radiation-sensitive following treatment with NanoOlaparib, a lipid-based injectable nanoformulation of Olaparib. This enhancement in radiosensitivity is accompanied by radiation dose-dependent changes in γ-H2AX expression and [...]

Menée à l'aide de cellules mammaires cancéreuses résistantes au tamoxifène et à l'aide de tissus tumoraux, cette étude met en évidence le rôle du facteur de transcription SOX9 dans la résistance des cellules tumorales aux traitements endocriniens

Embryonic transcription factor SOX9 drives breast cancer endocrine resistance

Jeselsohn, Rinath ; Cornwell, MacIntosh ; Pun, Matthew ; Buchwalter, Gilles ; Nguyen, Mai ; Bango, Clyde ; Huang, Ying ; Kuang, Yanan ; Paweletz, Cloud ; Fu, Xiaoyong ; Nardone, Agostina ; De Angelis, Carmine ; Detre, Simone ; Dodson, Andrew ; Mohammed, Hisham ; Carroll, Jason S. ; Bowden, Michaela ; Rao, Prakash ; Long, Henry W. ; Li, Fugen ; Dowsett, Mitchell ; Schiff, Rachel ; Brown, Myles

The estrogen receptor (ER) drives the growth of most luminal breast cancers and is the primary target of endocrine therapy. Although ER blockade with drugs such as tamoxifen is very effective, a major clinical limitation is the development of endocrine resistance especially in the setting of metastatic disease. Preclinical and clinical observations suggest that even following the development of endocrine resistance, ER signaling continues to exert a pivotal role in tumor progression in the [...]

A partir de donnés portant sur 1 551 patients atteints d'un mélanome de stade avancé et des recommandations de l'Agence européenne du médicament, cette étude passe en revue les événements indésirables liés aux immunothérapies à base d'inhibiteurs de point de contrôle (anti-PD-1 et anti-CTLA-4), tels que l'ipilimumab et le nivolumab, et présente des recommandations pour la prise en charge de ces toxicités

Combined immune checkpoint blockade (anti-PD-1/anti-CTLA-4): evaluation and management of adverse drug reactions

Hassel, Jessica C. ; Heinzerling, Lucie ; Aberle, Jens ; Bähr, Oliver ; Eigentler, Thomas K. ; Grimm, Marc-Oliver ; Grünwald, Victor ; Leipe, Jan ; Reinmuth, Niels ; Tietze, Julia K. ; Trojan, Jörg ; Zimmer, Lisa ; Gutzmer, Ralf

Combined immune checkpoint blockade (ICB) provides unprecedented efficacy gains in numerous cancer indications, with PD-1 inhibitor nivolumab plus CTLA-4 inhibitor ipilimumab in advanced melanoma as first-ever approved therapies for combined ICB. However, gains in efficacy must be balanced against a higher frequency and severity of adverse drug reactions (ADR). Because delays in diagnosis and management might result in symptom worsening and further complications, clinicians shall be well [...]

Mené sur des patients atteints d'un lymphome récidivant et/ou réfractaire, d'un myélome multiple ou d'une tumeur solide, puis sur 34 patients atteints d'un lymphome à cellules B, cet essai de phase I évalue les caractéristiques pharmacocinétiques, la dose maximale tolérée, l'efficacité, du point de vue du taux de réponse objective, et la toxicité de l'ajout du véliparib, un inhibiteur de PARP, à la bendamustine et au rituximab

The PARP Inhibitor Veliparib Can Be Safely Added to Bendamustine and Rituximab and Has Preliminary Evidence of Activity in B-Cell Lymphoma

Soumerai, Jacob D. ; Zelenetz, Andrew D. ; Moskowitz, Craig H. ; Palomba, M. Lia ; Hamlin, Paul A. ; Noy, Ariela ; Straus, David J. ; Moskowitz, Alison J. ; Younes, Anas ; Matasar, Matthew J. ; Horwitz, Steven M. ; Portlock, Carol S. ; Konner, Jason A. ; Gounder, Mrinal M. ; Hyman, David M. ; Voss, Martin H. ; Fury, Matthew G. ; Gajria, Devika ; Carvajal, Richard D. ; Ho, Alan L. ; Beumer, Jan H. ; Kiesel, Brian ; Zhang, Zhigang ; Chen, Alice ; Little, Richard F. ; Jarjies, Christine ; Dang, Thu O. ; France, Fallon ; Mishra, Nishant ; Gerecitano, John F.

Purpose: The PARP inhibitor veliparib enhances the cytotoxicity of alkylating agents. This phase I study evaluated veliparib with the bifunctional alkylator bendamustine (VB) in patients with relapsed/refractory lymphoma, multiple myeloma, and solid malignancies, with a cohort expansion of VB with rituximab (VBR) in patients with B-cell lymphomas. Experimental Design: This dose-escalation study evaluated safety, pharmacokinetics, and preliminary efficacy of veliparib (20–400 mg twice a day, [...]

Cette étude passe en revue les événements indésirables liés à un traitement par inhibiteurs de BRAF et de MEK chez des patients atteints d'un mélanome métastatique présentant la mutation V600 du gène BRAF, puis fait le point sur la prise en charge de ces effets indésirables

Management of Treatment-Related Adverse Events with Agents Targeting the MAPK Pathway in Patients with Metastatic Melanoma

Daud, Adil ; Tsai, Katy

Tremendous progress has been made in the clinical landscape of advanced‐stage BRAF V600–mutant melanoma treatment over the past 5 years. Targeted therapies that inhibit specific steps of the mitogen‐activated protein kinase pathway have been shown to provide significant overall treatment benefit in patients with this difficult‐to‐treat disease. Combination therapy with BRAF and MEK inhibitors (dabrafenib plus trametinib or vemurafenib plus cobimetinib, respectively) has become standard of care. [...]

A partir de données portant sur 66 patients atteints d'un mélanome et de métastases cérébrales, cette étude rétrospective évalue l'efficacité, du point de vue du taux de réponse au niveau intra-crânien, du taux de contrôle de la maladie et de la survie sans progression, de thérapies anti-PD-1 telles que le nivolumab et le pembrolizumab (durée médiane de suivi : 7 mois)

Efficacy of anti-PD-1 therapy in patients with melanoma brain metastases

Parakh, Sagun ; Park, John J. ; Mendis, Shehara ; Rai, Rajat ; Xu, Wen ; Lo, Serigne ; Drummond, Martin ; Rowe, Catherine ; Wong, Annie ; McArthur, Grant ; Haydon, Andrew ; Andrews, Miles C. ; Cebon, Jonathan ; Guminski, Alex ; Kefford, Richard F. ; Long, Georgina V. ; Menzies, Alexander M. ; Klein, Oliver ; Carlino, Matteo S.

Background: There is limited data on the efficacy of anti-programmed death 1 (PD-1) antibodies in patients (pts) with melanoma brain metastasis (BM), particularly those which are symptomatic. Method:We retrospectively assessed pts with melanoma BM treated with PD-1 antibodies, nivolumab and pembrolizumab. Clinicopathologic and treatment parameters were collected and outcomes determined for intracranial (IC) response rate (RR) using a modified RECIST criteria, with up to five IC target lesions [...]

A partir de données portant sur 233 patients atteints d'un myélome multiple réfractaire, cette étude rétrospective analyse l'efficacité, du point de vue du taux de réponse objective et de la survie sans progression, d'une greffe autologue de cellules souches hématopoïétiques (durée médiane de suivi : 42 mois)

Outcome of autologous hematopoietic stem cell transplantation in refractory multiple myeloma

Veltri, Lauren W. ; Milton, Denai R. ; Delgado, Ruby ; Shah, Nina ; Patel, Krina ; Nieto, Yago ; Kebriaei, Partow ; Popat, Uday R. ; Parmar, Simrit ; Oran, Betul ; Ciurea, Stefan ; Hosing, Chitra ; Lee, Hans C. ; Manasanch, Elisabet ; Orlowski, Robert Z. ; Shpall, Elizabeth J. ; Champlin, Richard E. ; Qazilbash, Muzaffar H. ; Bashir, Qaiser

BACKGROUND: Despite the introduction of effective, novel agents, the outcome of patients with refractory multiple myeloma remains poor, particularly those who are refractory to both proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs). Limited data are available on the role of autologous hematopoietic stem cell transplantation in this population. METHODS: Patients with refractory myeloma who underwent first autologous hematopoietic stem cell transplantation (auto-HCT) between March [...]

Mené sur 58 patients atteints d'un cancer du poumon à petites cellules (39 sensibles aux sels de platine et 19 réfractaires et/ou résistants), cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression à la semaine 8 du traitement, et la toxicité du pazopanib en traitement de seconde ligne

Second-line pazopanib in patients with relapsed and refractory small-cell lung cancer: a multicentre phase II study of the Hellenic Oncology Research Group

Koinis, F. ; Agelaki, S. ; Karavassilis, V. ; Kentepozidis, N. ; Samantas, E. ; Peroukidis, S. ; Katsaounis, P. ; Hartabilas, E. ; Varthalitis, I. I. ; Messaritakis, I. ; Fountzilas, G. ; Georgoulias, V. ; Kotsakis, A.

Background: Pazopanib is a tyrosine kinase inhibitor with antiangiogenic activity. Vascular endothelial growth factor expression is increased in SCLC and is correlated with poor prognosis. The efficacy and tolerance of second-line pazopanib in SCLC was evaluated. Patients and methods: Patients with platinum-sensitive (cohort A; n=39) and -resistant/refractory (cohort B; n=19) SCLC were enrolled in a multicentre phase II study. The primary end point was the progression-free survival rate (PFS-R) [...]

Mené au Japon sur 32 patients atteints d'un cancer du poumon non à petites cellules de stade avancé (âge médian : 78 ans), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité du carboplatine en combinaison avec du nab-paclitaxel

Phase II Study of Modified Carboplatin Plus Weekly Nab-Paclitaxel in Elderly Patients with Non-Small Cell Lung Cancer: North Japan Lung Cancer Study Group Trial 1301

Miyauchi, Eisaku ; Inoue, Akira ; Usui, Kazuhiro ; Sugawara, Shunichi ; Maemondo, Makoto ; Saito, Heisuke ; Fujita, Yuka ; Kato, Terufumi ; Suzuki, Toshiro ; Harada, Toshiyuki ; Watanabe, Hiroshi ; Nakagawa, Taku ; Ichinose, Masakazu

Background : The CA031 trial suggested weekly nanoparticle albumin‐bound‐paclitaxel (nab‐PTX) was superior in efficacy to paclitaxel (PTX) once every 3 weeks when combined with carboplatin (CBDCA) for advanced non‐small cell lung cancer (NSCLC) patients; a subgroup analysis of elderly patients looked promising. In a multicenter phase II trial, we prospectively evaluated the efficacy and tolerability of modified CBDCA plus weekly nab‐PTX for elderly patients with untreated advanced NSCLC. [...]

Mené en Allemagne sur 49 patients atteints d'un carcinome neuroendocrine à grandes cellules du poumon de stade avancé (âge moyen : 62 ans), cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité d'un traitement de première ligne combinant évérolimus, paclitaxel et carboplatine

Everolimus with paclitaxel and carboplatin as first-line treatment for metastatic large-cell neuroendocrine lung carcinoma: a multicenter phase II trial

P. Christopoulos, ; W. Engel-Riedel, ; C. Grohé, ; C. Kropf-Sanchen, ; J. von Pawel, ; S. Gütz, ; J. Kollmeier, ; W. Eberhardt, ; D. Ukena, ; V. Baum

Background: Large cell neuroendocrine carcinoma of the lung (LCNEC) is a rare disease with poor prognosis and limited treatment options. Neuroendocrine tumors frequently show overactivation of the mTOR pathway. Based on the good activity of the mTOR inhibitor everolimus in different types of neuroendocrine tumors and the results of a previous phase I trial we evaluated the efficacy and safety of everolimus in combination with carboplatin and paclitaxel as upfront treatment for patients with [...]

Menée aux Etats-Unis auprès de 90 patients atteints d'un carcinome à cellules rénales de stade métastatique, cette étude prospective évalue les facteurs associés à la survenue d'événements cardiotoxiques liés au sunitinib

Prospective Evaluation of Sunitinib-Induced Cardiotoxicity in Patients with Metastatic Renal Cell Carcinoma

Narayan, Vivek ; Keefe, Stephen ; Haas, Naomi ; Wang, Le ; Puzanov, Igor ; Putt, Mary ; Catino, Anna ; Fang, James ; Agarwal, Neeraj ; Hyman, David ; Smith, Amanda M. ; Finkelman, Brian S. ; Narayan, Hari K. ; Ewer, Steven ; ElAmm, Chantal ; Lenihan, Daniel ; Ky, Bonnie

Purpose: To prospectively evaluate cardiotoxicity risk with sunitinib in metastatic renal cell carcinoma (mRCC) routine clinical practice using comprehensive echocardiography and biomarker phenotyping. Patients and Methods: In a multicenter prospective study of 90 patients with mRCC, echocardiography and biomarkers of cardiovascular injury and stress were quantified at baseline, 3.5, 15, and 33 weeks following sunitinib initiation. These “on-drug” visits corresponded to cycles 1, 3, and 6, [...]

A partir des données de deux essais de phase II menés sur 66 patients atteints d'un sarcome lié à une translocation chromosomique et de stade avancé, cette étude évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale, de la trabectédine

Efficacy of Trabectedin in Patients With Advanced Translocation-Related Sarcomas: Pooled Analysis of Two Phase II Studies

Takahashi, Mitsuru ; Takahashi, Shunji ; Araki, Nobuhito ; Sugiura, Hideshi ; Ueda, Takafumi ; Yonemoto, Tsukasa ; Morioka, Hideo ; Hiraga, Hiroaki ; Hiruma, Toru ; Kunisada, Toshiyuki ; Matsumine, Akihiko ; Shimura, Masashi ; Kawai, Akira

Trabectedin is reported as effective, especially against translocation‐related sarcomas (TRSs) after failure of or intolerance to standard chemotherapy. We conducted two phase II studies of TRS, confirming high efficacy of 1.2 mg/m2 trabectedin. The updated data of 66 patients in these studies was integrated to evaluate the efficacy of trabectedin against each histological subtype, and analyze final overall survival (OS).Trabectedin was administered on day one of a 21‐day cycle. Efficacy was [...]

A partir des données d'un essai international de phase III mené sur 1 144 patientes atteintes d'un cancer du sein HER2- de stade avancé, cette étude rétrospective évalue l'efficacité, du point de vue du taux de réponse globale, de l'amélioration de la survie sans progression et de la survie globale, de médicaments bêta-bloquants

Beta Blockers and Improved Progression Free Survival in Patients with Advanced HER2 Negative Breast Cancer: a Retrospective Analysis of the ROSE/TRIO-012 Study

G. Spera, ; R. Fresco, ; H. Fung, ; J. R. B. Dyck, ; E. Pituskin, ; I. Paterson, ; J. R. Mackey

Background: Recent retrospective studies suggest that beta-adrenergic blocking drugs (BB) are associated with improved outcomes in people with a range of cancers. Although limited and discordant data suggest that BB may increase overall survival (OS) of patients with localized breast cancer (BC), there is no information on the effects of BB in women with advanced BC. Patients and Methods: To explore the association between BB use and BC outcomes, we retrospectively reviewed the ROSE/TRIO-012, a [...]

Cette étude passe en revue les immunothérapies utilisées pour le traitement de patients atteints d'un carcinome épidermoïde de la tête et du cou

Immunotherapy for Head and Neck Squamous Cell Carcinoma: A Review of Current and Emerging Therapeutic Options

Moskovitz, Jessica M. ; Moy, Jennifer ; Seiwert, Tanguy Y. ; Ferris, Robert L.

Advances in the field of cancer immunotherapy have occurred rapidly over the past decade. Exciting results from clinical trials have led to new treatment options and improved survival for patients with a myriad of solid tumor pathologies. However, questions remain unanswered regarding duration and timing of therapy, combination regimens, appropriate biomarkers of disease, and optimal monitoring of therapeutic response. This article reviews emerging immunotherapeutic agents and significant [...]

Menée à partir de données portant sur 80 patients atteints d'un lymphome hodgkinien réfractaire aux traitements ou récidivant traité entre 2005 et 2014 (durée médiane de suivi : 25 mois), cette étude évalue, du point de vue de la survie sans progression et de la survie globale à 2 ans, l'intérêt d'ajouter une radiothérapie de consolidation à un traitement comportant une chimiothérapie à haute dose et une greffe autologue de cellules souches hématopoïétiques

The role of consolidative radiotherapy following autologous hematopoietic cell transplantation for the treatment of relapsed or refractory Hodgkin lymphoma

Wilke, Chris ; Cao, Qing ; Dusenbery, Kathryn E. ; Bachanova, Veronika ; Lazaryan, Aleksandr ; Lee, Chung K. ; Yuan, Jianling

Purpose : To evaluate the role of the addition of consolidative radiotherapy following high-dose chemotherapy and autologous hematopoietic cell transplantation (AHCT) for relapsed or refractory Hodgkin lymphoma (HL). Methods and Materials : Medical records were reviewed from a total of 80 consecutive patients who underwent high-dose chemotherapy with AHCT treated under a single protocol at XXXX between 11/2005 – 1/2014. Of these, 32 patients received radiotherapy following AHCT as planned [...]

Menée à partir de données portant sur 406 patients atteints d'un cancer rectal de stade T3 traité entre 2007 et 2013 (durée médiane de suivi : 45 mois), cette étude coréenne compare, du point de vue de la survie sans récidive locale, de la survie sans maladie et de la survie globale, l'efficacité d'une exérèse localisée et d'une résection mésorectale totale après une chimioradiothérapie dont les résultats se sont avérés favorables

Total Mesorectal Excision Versus Local Excision Following Favorable Response to Preoperative Chemoradiotherapy in “Early” Clinical T3 Rectal Cancer : A Propensity Score Analysis

Shin, Young Seob ; Yu, Chang Sik ; Park, Jin-hong ; Kim, Jin Cheon ; Lim, Seok-Byung ; Park, In Ja ; Kim, Tae Won ; Hong, Yong Sang ; Kim, Kyu-pyo ; Yoon, Sang Min ; Joo, Ji Hyeon ; Kim, Jong Hoon

Purpose : The aim of this study was to compare oncological outcomes of total mesorectal excision (TME) and local excision (LE) in patients with “early” clinical T3 rectal cancer who received preoperative chemoradiotherapy (PCRT). Methods and Materials : “Early” clinical T3 rectal cancer was radiologically defined as tumors with extramural extension of <5 mm without mesorectal fascia involvement and lateral lymph node metastasis. Patients with “early” clinical T3 rectal cancer who received PCRT [...]

Mené sur 46 patients atteints d'un glioblastome récemment diagnostiqué et recevant un traitement standard combinant résection, radiothérapie et chimiothérapie, cet essai de phase II évalue, du point de vue de la survie globale et en fonction du niveau d'expression de PD-L1 sur les cellules myéloïdes périphériques, l'efficacité d'un vaccin autologue à base de peptides provenant de protéines HSP (Heat Shock Protein ) de cellules tumorales

Autologous Heat Shock Protein Peptide Vaccination for Newly Diagnosed Glioblastoma : Impact of Peripheral PD-L1 Expression on Response to Therapy

Bloch, Orin ; Lim, Michael ; Sughrue, Michael E. ; Komotar, Ricardo J. ; Abrahams, John M. ; Rourke, Donald M. ; Ambrosio, Anthony ; Bruce, Jeffrey N. ; Parsa, Andrew T.

Purpose : Standard therapy for newly diagnosed glioblastoma (GBM) is surgical resection, followed by concurrent radiotherapy and temozolomide chemotherapy. In this phase II clinical trial, the addition of an autologous heat-shock protein vaccine to standard therapy was evaluated. Tumor-induced immunosuppression, mediated by expression of PD-L1 on tumor and circulating immune cells, may impact the efficacy of vaccination. Expression of PD-L1 on peripheral myeloid cells was evaluated for the [...]

Cet article passe en revue les travaux récents sur le rôle du microbiome dans le développement et le traitement d'une tumeur

Anticancer effects of the microbiome and its products

Zitvogel, Laurence ; Daillère, Romain ; Roberti, Maria Paula ; Routy, Bertrand ; Kroemer, Guido

The human gut microbiome modulates many host processes, including metabolism, inflammation, and immune and cellular responses. It is becoming increasingly apparent that the microbiome can also influence the development of cancer. In preclinical models, the host response to cancer treatment has been improved by modulating the gut microbiome; this is known to have an altered composition in many diseases, including cancer. In addition, cancer treatment with microbial agents or their products has [...]

Cet article passe en revue les études sur les inhibiteurs de l'enzyme mTOR, leur toxicité et les mécanismes de résistance dans le traitement des tumeurs neuroendocrines du pancréas

Critical focus on mechanisms of resistance and toxicity of m-TOR inhibitors in pancreatic neuroendocrine tumors

Antonuzzo, L. ; Del Re, M. ; Barucca, V. ; Spada, F. ; Meoni, G. ; Restante, G. ; Danesi, R. ; Costanzo, F. Di ; Fazio, N.

Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms representing less than 2% of all pancreatic malignancies. The PI3K-AKT-mTOR pathway is often deregulated in pNETs and seems to play a key role in tumorigenesis. Everolimus, an inhibitor of the mTOR pathway, has demonstrated efficacy in the treatment of pNETs. Nevertheless de novo or acquired drug resistance is responsible for disease progression and represents a major obstacle to overcome by clinicians. Blocking the PI3K/AKT/mTOR [...]

Cet article passe en revue les mécanismes de résistance dans le traitement systémique des cancers métastatiques de la prostate résistant à la castration

Mechanisms of resistance to systemic therapy in metastatic castration-resistant prostate cancer

Galletti, Giuseppe ; Leach, Benjamin I. ; Lam, Linda ; Tagawa, Scott T.

Patients with metastatic castration-resistant prostate cancer (mCPRC) now have an unprecedented number of approved treatment options, including chemotherapies (docetaxel, cabazitaxel), androgen receptor (AR)-targeted therapies (enzalutamide, abiraterone), a radioisotope (radium-223) and a cancer vaccine (sipuleucel-T). However, the optimal treatment sequencing pathway is unknown, and this problem is exacerbated by the issues of primary and acquired resistance. This review focuses on mechanisms [...]

A partir d'un exemple d'essai clinique incluant des patientes atteintes d'un cancer du sein ER+ HER2- de stade avancé, cette étude évalue l'intérêt d'une méthodologie consistant à ajouter un bras de traitement à un essai clinique standard

Designing Clinical Trials That Accept New Arms: An Example in Metastatic Breast Cancer

Steffen Ventz ; Brian M. Alexander ; Giovanni Parmigiani ; Richard D. Gelber ; Lorenzo Trippa

Purpose : The majority of randomized oncology trials are two-arm studies that test the efficacy of new therapies against a standard of care, thereby assigning a large proportion of patients to nonexperimental therapies. In contrast, multiarm studies efficiently share a common control arm while evaluating multiple experimental therapies. A major bottleneck for traditional multiarm trials is the requirement that all therapies—often drugs from different companies—have to be available at the same [...]