Mené sur 99 patients présentant 1 à 5 oligométastases (durée médiane de suivi : 51 mois), cet essai de phase II évalue l'intérêt, du point de vue de la survie globale, de la survie sans progression, de la toxicité et de la qualité de vie des patients, d'une radiothérapie stéréotaxique ablative

Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial

Palma, David A. ; Olson, Robert ; Harrow, Stephen ; Gaede, Stewart ; Louie, Alexander V. ; Haasbeek, Cornelis ; Mulroy, Liam ; Lock, Michael ; Rodrigues, George B. ; Yaremko, Brian P. ; Schellenberg, Devin ; Ahmad, Belal ; Senthi, Sashendra ; Swaminath, Anand ; Kopek, Neil ; Liu, Mitchell ; Moore, Karen ; Currie, Suzanne ; Schlijper, Roel ; Bauman, Glenn S. ; Laba, Joanna ; Qu, X. Melody ; Warner, Andrew ; Senan, Suresh

PURPOSE : The oligometastatic paradigm hypothesizes that patients with a limited number of metastases may achieve long-term disease control, or even cure, if all sites of disease can be ablated. However, long-term randomized data that test this paradigm are lacking. METHODS : We enrolled patients with a controlled primary malignancy and 1-5 metastatic lesions, with all metastases amenable to stereotactic ablative radiotherapy (SABR). We stratified by the number of metastases (1-3 v 4-5) and [...]

A partir d'une revue systématique de la littérature publiée entre janvier 2000 et décembre 2019 (9 études incluant au total 460 patients), cette étude analyse l'efficacité et la sécurité d'une électroporation irréversible par voie ouverte chez les patients atteints d'un cancer du pancréas

The efficacy and safety of the open approach irreversible electroporation in the treatment of pancreatic cancer: A systematic review

Charalambous, Pabos ; Moris, Dimitrios ; Karachaliou, Georgia-Sofia ; Papalampros, Alexandros ; Dimitrokallis, Nikolaos ; Tsilimigras, Diamantis I. ; Oikonomou, Dimitrios ; Petrou, Athanasios

Background : Irreversible Electroporation (IRE) is a novel non-thermal ablation technique used in patients with locally advanced pancreatic cancer (LAPC), in the proximity of sensitive structures such as vessels, intestinal wall and the bile duct. Currently, it is only used in the setting of clinical trials. This systematic review aimed to tackle the knowledge gap in the literature, in relation to the safety and efficacy of the open approach IRE. Methods : MEDLINE, EMBASE and Cochrane libraries [...]

Menée au Royaume-Uni à partir de données portant sur 2 792 patientes âgées d'au moins 70 ans et atteintes d'un cancer du sein (âge médian : 76 ans), cette étude identifie les facteurs associés à une mastectomie et à une chirurgie axillaire puis évalue le taux d'événements indésirables

Breast cancer surgery in older women: outcomes of the Bridging Age Gap in Breast Cancer study

Morgan, J. L. ; George, J. ; Holmes, G. ; Martin, C. ; Reed, M. W. R. ; Ward, S. ; Walters, S. J. ; Cheung, K. Leung ; Audisio, R. A. ; Wyld, L. ; Bridging the Age Gap Trial Management, Team

Background : Breast cancer surgery in older women is variable and sometimes non‐standard owing to concerns about morbidity. Bridging the Age Gap in Breast Cancer is a prospective multicentre cohort study aiming to determine factors influencing treatment selection and outcomes from surgery for older patients with breast cancer. Methods : Women aged at least 70 years with operable breast cancer were recruited from 57 UK breast units between 2013 and 2018. Associations between patient and tumour [...]

Menée in vitro et à l'aide de modèles murins, cette étude met en évidence un mécanisme par lequel le contact direct entre les fibroblastes associés au cancer et les cellules cancéreuses active, via la protéine STING et le facteur IRF3 des fibroblastes, l'expression de cytokines et réduit l'efficacité des virus oncolytiques

STING and IRF3 in stromal fibroblasts enable sensing of genomic stress in cancer cells to undermine oncolytic viral therapy

Arwert, Esther N. ; Milford, Emma L. ; Rullan, Antonio ; Derzsi, Stefanie ; Hooper, Steven ; Kato, Takuya ; Mansfield, David ; Melcher, Alan ; Harrington, Kevin J. ; Sahai, Erik

Cancer-associated fibroblasts (CAFs) perform diverse roles and can modulate therapy responses1. The inflammatory environment within tumours also influences responses to many therapies, including the efficacy of oncolytic viruses2; however, the role of CAFs in this context remains unclear. Furthermore, little is known about the cell signalling triggered by heterotypic cancer cell–fibroblast contacts and about what activates fibroblasts to express inflammatory mediators1,3. Here, we show that [...]

Menée in vitro et à l'aide de modèles murins, cette étude met en évidence l'intérêt d'une stratégie, consistant à fusionner des épitopes spécifiques de la tumeur à une protéine porteuse choisie en fonction de ses propriétés pharmacocinétiques, pour améliorer l'immunogénicité des vaccins sous-unitaires

Pharmacokinetic tuning of protein–antigen fusions enhances the immunogenicity of T-cell vaccines

Mehta, Naveen K. ; Pradhan, Roma V. ; Soleimany, Ava P. ; Moynihan, Kelly D. ; Rothschilds, Adrienne M. ; Momin, Noor ; Rakhra, Kavya ; Mata-Fink, Jordi ; Bhatia, Sangeeta N. ; Wittrup, K. Dane ; Irvine, Darrell J.

The formulations of peptide-based antitumour vaccines being tested in clinical studies are generally associated with weak potency. Here, we show that pharmacokinetically tuning the responses of peptide vaccines by fusing the peptide epitopes to carrier proteins optimizes vaccine immunogenicity in mice. In particular, we show in immunized mice that the carrier protein transthyretin simultaneously optimizes three factors: efficient antigen uptake in draining lymphatics from the site of injection, [...]

Menée in vitro et à l'aide d'un modèle murin, cette étude met en évidence un mécanisme par lequel le granzyme A (une sérine protéase) issu des lymphocytes cytotoxiques clive et active la gasdermine B, une protéine impliquée dans la pyroptose, puis démontre que l'expression forcée de la gasdermine B dans les cellules cancéreuses favorise l'élimination de la tumeur

Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells

Zhou, Zhiwei ; He, Huabin ; Wang, Kun ; Shi, Xuyan ; Wang, Yupeng ; Su, Ya ; Wang, Yao ; Li, Da ; Liu, Wang ; Zhang, Yongliang ; Shen, Lianjun ; Han, Weidong ; Shen, Lin ; Ding, Jingjin ; Shao, Feng

Cytotoxic T cells and natural killer cells use several strategies to kill infected or transformed cells. One such pathway entails the delivery of a family of serine proteases called granzymes to target cells through perforin-mediated pores to induce a form of programmed cell death called apoptosis. Zhou et al. show that granzyme A cleaves and activates gasdermin B (GSDMB), a central player in the highly inflammatory cell death process known as pyroptosis (see the Perspective by Nicolai and [...]

Menée in vitro et à l'aide de modèles murins, cette étude étude met en évidence l'intérêt d'inhiber la voie de signalisation JAK/STAT et la déméthylsase LSD1 pour traiter une leucémie myéloïde aiguë avec mutation des gènes CSF3R/CEBPA

Combined inhibition of JAK/STAT pathway and lysine-specific demethylase 1 as a therapeutic strategy in CSF3R/CEBPA mutant acute myeloid leukemia

Braun, Theodore P. ; Coblentz, Cody ; Smith, Brittany M. ; Coleman, Daniel J. ; Schonrock, Zachary ; Carratt, Sarah A. ; Callahan, Rowan L. ; Maniaci, Breanna ; Druker, Brian J. ; Maxson, Julia E.

Acute myeloid leukemia is a blood cancer that has poor outcomes with conventional treatment. The clinical behavior of the disease is driven in large part by the gene mutations that are responsible for disease development. The combination of mutations in the genes CEBPA and CSF3R is associated with an increased risk of recurrent disease after standard therapy. We have identified a drug combination that blocks signaling through the JAK/STAT pathway and inhibits the epigenetic regulator LSD1. This [...]

Menée à l'aide de lignées cellulaires, d'échantillons de mésothéliomes pleuraux ou péritonéaux diffus et de modèles murins, cette étude analyse la corrélation entre hypoxie, niveau d'expression du transporteur de folate couplé aux protons et chimiorésistance des cellules cancéreuses, puis évalue l'activité antitumorale de nouveaux inhibiteurs de la lactate déshydrogénase LDH-A

Impact of hypoxia on chemoresistance of mesothelioma mediated by the proton-coupled folate transporter, and preclinical activity of new anti-LDH-A compounds

Li Petri, Giovanna ; El Hassouni, Btissame ; Sciarrillo, Rocco ; Funel, Niccola ; Mantini, Giulia ; Zeeuw van der Laan, Eveline A. ; Cascioferro, Stella ; Avan, Amir ; Zucali, Paolo Andrea ; Zaffaroni, Nadia ; Lagerweij, Tonny ; Parrino, Barbara ; Smid, Kees ; Deraco, Marcello ; Granchi, Carlotta ; Braczko, Alicja ; Smolenski, Ryszard T. ; Matherly, Larry H. ; Jansen, Gerrit ; Assaraf, Yehuda G. ; Diana, Patrizia ; Cloos, Jacqueline ; Peters, Godefridus J. ; Minutolo, Filippo ; Giovannetti, Elisa

Background : Expression of proton-coupled folate transporter (PCFT) is associated with survival of mesothelioma patients treated with pemetrexed, and is reduced by hypoxia, prompting studies to elucidate their correlation. Methods : Modulation of glycolytic gene expression was evaluated by PCR arrays in tumour cells and primary cultures growing under hypoxia, in spheroids and after PCFT silencing. Inhibitors of lactate dehydrogenase (LDH-A) were tested in vitro and in vivo. LDH-A expression was [...]

Menée in vitro, cette étude met en évidence l'intérêt de réactiver sélectivement la voie de signalisation de la protéine STING pour traiter un carcinome à cellules de Merkel

Selective reactivation of STING signaling to target Merkel cell carcinoma

Liu, Wei ; Kim, Gloria B. ; Krump, Nathan A. ; Zhou, Yuqi ; Riley, James L. ; You, Jianxin

The immune-dampened status of Merkel cell carcinoma (MCC) tumors presents a major obstacle to developing effective immunotherapies. We propose that STING silencing may cause the immunologically “cold” MCC tumor microenvironments by blocking cytokine production and, consequently, impeding cytotoxic T cell infiltration, activation, and killing of tumor cells. Our findings indicate that targeted activation of STINGS162A/G230I/Q266I by DMXAA could be a viable strategy for bolstering antitumor [...]

Menée à l'aide de lignées cellulaires, d'échantillons tumoraux issus de patients atteints d'un cancer colorectal métastatique et de xénogreffes sur des modèles murins, cette étude met en évidence un mécanisme par lequel la metformine, en raison de la suppression de l'expression de la protéine MATE1 par les oncoprotéines KRAS mutées, peut s'accumuler dans les cellules cancéreuses avec mutation du gène KRAS et inhiber leur développement

Metformin selectively inhibits metastatic colorectal cancer with the KRAS mutation by intracellular accumulation through silencing MATE1

Xie, Jinye ; Xia, Liangping ; Xiang, Wei ; He, Wenzhuo ; Yin, Haofan ; Wang, Fang ; Gao, Tianxiao ; Qi, Weiwei ; Yang, Zhonghan ; Yang, Xia ; Zhou, Ti ; Gao, Guoquan

CRC patients with KRAS mutations are confronted with limited targeted therapeutic options. In this study, we have shown that the median survival time for KRAS-mutation mCRC patients with diabetes on metformin is 37.8 mo longer than those treated with other hypoglycemic drugs in combination with standard systemic therapy. Metformin is preferentially accumulated in KRAS-mutation CRC cells in both primary cell cultures and patient-derived xenografts. The promising therapeutic activity of metformin [...]

Menée à l'aide de lignées cellulaires de neuroblastome et d'une xénogreffe sur un modèle murin, cette étude met en évidence l'efficacité antitumorale du régorafénib et démontre que ce dernier inhibe les voies de signalisation RAS/MAPK, PI3K/Akt/mTOR et Fos/Jun

Regorafenib is effective against neuroblastoma in vitro and in vivo and inhibits the RAS/MAPK, PI3K/Akt/mTOR and Fos/Jun pathways

Subramonian, Divya ; Phanhthilath, Nikki ; Rinehardt, Hannah ; Flynn, Sean ; Huo, Yuchen ; Zhang, Jing ; Messer, Karen ; Mo, Qianxing ; Huang, Shixia ; Lesperance, Jacqueline ; Zage, Peter E.

Background : Regorafenib is an inhibitor of multiple kinases with aberrant expression and activity in neuroblastoma tumours that have potential roles in neuroblastoma pathogenesis. Methods : We evaluated neuroblastoma cells treated with regorafenib for cell viability and confluence, and analysed treated cells for apoptosis and cell cycle progression. We evaluated the efficacy of regorafenib in vivo using an orthotopic xenograft model. We evaluated regorafenib-mediated inhibition of kinase [...]

Mené sur 67 patients atteints d’un carcinome œsogastrique de stade avancé, cet essai de phase II non randomisé évalue l’efficacité, du point de vue du taux de réponse objective, et la toxicité d’un traitement de première ligne de type FOLFIRINOX (leucovorine, fluorouracile, irinotécan et oxaliplatine ; durée médiane de suivi : 17,4 mois)

FOLFIRINOX for the Treatment of Advanced Gastroesophageal Cancers : A Phase 2 Nonrandomized Clinical Trial

Haeseong Park, Ramon U. Jin, Andrea Wang-Gillam (et al.)

Importance : Standard first-line regimens for patients with metastatic gastroesophageal adenocarcinomas have an approximate 40% objective response rate (ORR). The combination of leucovorin, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) has been efficacious as first-line therapy for other gastrointestinal cancers, such as pancreatic and colon cancers. Objective : To evaluate the clinical activity and safety of FOLFIRINOX as first-line treatment for patients with advanced [...]

Mené sur 397 patients atteints d’une tumeur stromale gastro-intestinale à haut risque de récidive, cet essai de phase III évalue l’efficacité, du point de vue de la survie sans récidive et de la survie globale, et la toxicité d’un traitement adjuvant par imatinib dispensé pendant une durée de 1 ou 3 ans (durée médiane de suivi : 119 mois)

Survival Outcomes Associated With 3 Years vs 1 Year of Adjuvant Imatinib for Patients With High-Risk Gastrointestinal Stromal Tumors : An Analysis of a Randomized Clinical Trial After 10-Year Follow-up

Heikki Joensuu, Mikael Eriksson, Kirsten Sundby Hall (et al.)

Importance : Adjuvant imatinib is associated with improved recurrence-free survival (RFS) when administered after surgery to patients with operable gastrointestinal stromal tumor (GIST), but its influence on overall survival (OS) has remained uncertain. Objective : To evaluate the effect of adjuvant imatinib on OS of patients who have a high estimated risk for GIST recurrence after macroscopically complete surgery. Design, Setting, and Participants : In this open-label, randomized (1:1), [...]

Mené sur 187 patients atteints d’un cancer de l’estomac HER2+ de stade avancé, cet essai de phase II compare l’efficacité, du point de vue du taux de réponse objective, et la toxicité du trastuzumab déruxtécan (un conjugué anticorps médicament ciblant HER2) et une chimiothérapie choisie par le médecin (irinotécan ou paclitaxel) après l’échec d'au moins deux thérapies

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer

Kohei Shitara, Yung-Jue Bang, Satoru Iwasa (et al.)

Background : Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate consisting of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor. The drug may have efficacy in patients with HER2-positive advanced gastric cancer. Methods : In an open-label, randomized, phase 2 trial, we evaluated trastuzumab deruxtecan as compared with chemotherapy in patients with HER2-positive advanced gastric cancer. [...]

Cette étude passe en revue les avancées récentes et les enjeux liés à l’utilisation des immunothérapies chez des patients atteints d’un cancer gastro-intestinal

Immunotherapy in gastrointestinal cancer: the current scenario and future perspectives

Mohammed Abdul-Latif, Katherine Townsend, Charles Dearman (et al.)

Gastrointestinal cancers include colorectal, gastric, oesophageal, pancreatic and liver cancers. They continue to be a significant cause of mortality and morbidity worldwide. Current treatment strategies include chemotherapy, surgery, radiotherapy and targeted therapies. Immunotherapy has recently been incorporated in treatment regimens for some gastrointestinal malignancies and research into different immune modifying treatments is being carried out in this context. Approaches to immune [...]

Mené sur 48 patients atteints d’une tumeur présentant des altérations des gènes FGFR, cet essai de phase II évalue l’efficacité, du point de vue du taux de réponse, de AZD4547, un inhibiteur de FGFR1-3 dispensé par voie orale

Phase II Study of AZD4547 in Patients With Tumors Harboring Aberrations in the FGFR Pathway: Results From the NCI-MATCH Trial (EAY131) Subprotocol W

Young K. Chae, Fangxin Hong, Christos Vaklavas (et al.)

PURPOSE : NCI-MATCH is a nationwide, histology-agnostic, signal-finding, molecular profile–driven trial for patients with refractory cancers, lymphomas, or myelomas. Patients with tumors harboring actionable aberration(s) in fibroblast growth factor receptor (FGFR) 1-3 were treated with AZD4547, an oral FGFR1-3 inhibitor. METHODS : Patients’ tumors were screened by next-generation sequencing for predefined FGFR amplification, activating mutations, or fusions. Patients were treated with AZD4547, [...]

Mené sur 310 patients atteints d’une leucémie lymphoïde chronique réfractaire ou récidivante, cet essai de phase III compare l’efficacité, du point de vue de la survie sans progression, et la toxicité de l’acalabrutinib en monothérapie et d’un traitement à base de rituximab choisi par le médecin (idélalisib/rituximab ou bendamustine/rituximab ; durée médiane de suivi ; 16,1 mois)

ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia

Paolo Ghia, Andrzej Pluta, Malgorzata Wach (et al.)

PURPOSE : Acalabrutinib, a highly selective, potent, Bruton tyrosine kinase inhibitor, was evaluated in this global, multicenter, randomized, open-label, phase III study in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). METHODS : Eligible patients, aged ? 18 years with R/R CLL, were randomly assigned 1:1 centrally and stratified by del(17p) status, Eastern Cooperative Oncology Group performance status score, and number of prior lines of therapy. Patients received [...]

Menée sur 113 patients atteints d’un lymphome de Burkitt (âge médian : 49 ans), cette étude évalue l’efficacité, du point de vue de la survie sans événement, et la toxicité d’une chimiothérapie de type EPOCH-R à doses ajustées (étoposide, doxorubicine, cyclophosphamide, vincristine, prednisone et rituximab ; durée médiane de suivi : 58,7 mois)

Multicenter Study of Risk-Adapted Therapy With Dose-Adjusted EPOCH-R in Adults With Untreated Burkitt Lymphoma

Mark Roschewski, Kieron Dunleavy, Jeremy S. Abramson (et al.)

PURPOSE : Burkitt lymphoma is an aggressive B-cell lymphoma curable with dose-intensive chemotherapy derived from pediatric leukemia regimens. Treatment is acutely toxic with late sequelae. We hypothesized that dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (DA-EPOCH-R) may obviate the need for highly dose-intensive chemotherapy in adults with Burkitt lymphoma. METHODS : We conducted a multicenter risk-adapted study of DA-EPOCH-R in untreated [...]

Mené en France sur 328 enfants (âge inférieur à 18 ans) atteints d’un lymphome non hodgkinien à cellules B matures de haut grade et à haut risque de récidive, cet essai de phase III évalue l’efficacité, du point de vue de la survie sans événement, et la toxicité de l’ajout du rituximab à une chimiothérapie standard (durée médiane de suivi : 39,9 mois)

Rituximab for High-Risk, Mature B-Cell Non-Hodgkin’s Lymphoma in Children

Véronique Minard-Colin, Anne Aupérin, Marta Pillon (et al.)

Background : Rituximab added to chemotherapy prolongs survival among adults with B-cell cancer. Data on its efficacy and safety in children with high-grade, mature B-cell non-Hodgkin’s lymphoma are limited. Methods : We conducted an open-label, international, randomized, phase 3 trial involving patients younger than 18 years of age with high-risk, mature B-cell non-Hodgkin’s lymphoma (stage III with an elevated lactate dehydrogenase level or stage IV) or acute leukemia to compare the addition [...]

Mené sur 86 patients atteints d’un lymphome à cellules du manteau réfractaire ou récidivant (âge médian : 60,5 ans), cet essai de phase II évalue l’efficacité, du point de vue du taux de réponse globale, et la toxicité du zanubrutinib, un inhibiteur de tyrosine kinase de Bruton

Treatment of Patients with Relapsed or Refractory Mantle Cell Lymphoma With Zanubrutinib, a Selective Inhibitor of Bruton's Tyrosine Kinase

Yuqin Song, Ke-Shu Zhou, Dehui Zou, Jianfeng Zhou (et al.)

Purpose Mantle-cell lymphoma (MCL) is an incurable mature B-cell neoplasm with high initial response rates followed almost invariably by relapse. Prognosis for patients following relapse is poor, and treatment choices are limited. We evaluated the efficacy and safety of zanubrutinib, an investigational selective Bruton's tyrosine kinase (BTK) inhibitor. Patients and Methods Patients with relapsed/refractory MCL were enrolled in this ongoing phase 2, single-arm, open-label study and treated with [...]

Mené sur 111 patients atteints d’un lymphome diffus à grandes cellules B à haut risque de récidive (âge médian : 50 ans), cet essai de phase II évalue l’efficacité, du point de vue de la survie sans progression à 2 ans, d’une stratégie de chimiothérapie de première ligne de type R-CODOX-M/R-IVAC (alternance par cycles d’un traitement combinant cyclophosphamide, vincristine, doxorubicine et hautes doses de méthotrexate, puis d’un traitement combinant ifosfamide, étoposide et hautes doses de cytarabine, tous deux dispensés avec le rituximab)

Favourable Outcomes for High-Risk Diffuse Large B-Cell Lymphoma (IPI 3-5) Treated with Front-Line R-CODOX-M/R-IVAC Chemotherapy: Results of a Phase 2 UK NCRI Trial

A.K.McMillan, E.H.Phillips, A.A.Kirkwood, S.Barrans (et al.)

Background : Outcomes for patients with high-risk diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP chemotherapy are suboptimal but, to date, no alternative regimen has been shown to improve survival rates. This phase 2 trial aimed to assess the efficacy of a Burkitt-like approach for high-risk DLBCL using the dose-intense R-CODOX-M/R-IVAC regimen. Patients and methods : Eligible pts were aged 18-65 years with stage II-IV untreated DLBCL and an International Prognostic Index (IPI) score [...]

Menée aux Etats-Unis à partir de données portant sur 383 patients atteints d’un mélanome de stade avancé traité entre 2009 et 2019, cette étude analyse l’efficacité des anti-PD-1/PD-L1 du point de vue du taux de réponse objective, de la survie globale et de la survie sans progression

Outcomes after progression of disease with anti–PD-1/PD-L1 therapy for patients with advanced melanoma

James R. Patrinely Jr, Laura X. Baker, Elizabeth J. Davis MD (et al.)

Background : Greater than one?half of patients with melanoma who are treated with antibodies blocking programmed cell death protein 1 receptor (anti–PD?1) experience disease progression. The objective of the current study was to identify prognostic factors and outcomes in patients with metastatic melanoma that progressed while they were receiving anti–PD?1 therapy. Methods : The authors evaluated 383 consecutively treated patients who received anti–PD?1 for advanced melanoma between 2009 and [...]

A partir d’une revue des essais de phase II et III (12 essais, 5 171 patientes), cette méta-analyse évalue l’efficacité et la toxicité des inhibiteurs de PARP, seuls ou en combinaison avec une chimiothérapie et/ou une thérapie ciblée, chez des patientes atteintes d’un cancer de l’ovaire de stade avancé ou récidivant

Incorporating parp-inhibitors in primary and recurrent ovarian cancer: a meta-analysis of 12 phase II/III randomized controlled trials

Ilary Ruscito, Filippo Bellati, Isabelle Ray-Coquard (et al.)

Background : The second decade of 2000s is witnessing a new ovarian cancer (OC) paradigm shift thanks to the results recently obtained by a new class of targeted agents: the Poly(ADP-ribose)polymerase (PARP)-Inhibitors (PARPi). Aim of this meta-analysis is to analyze available results obtained with PARPi, administered alone or in combination with chemo- and/or target-therapies in terms of efficacy and safety for the treatment of recurrent and primary advanced OC. Methods : On December 2019, all [...]

Mené sur 453 patients atteints d’un cancer du poumon à petites cellules de stade étendu, cet essai de phase III évalue l’efficacité, du point de vue de la survie sans progression et de la survie globale, et la toxicité de l’ajout du pembrolizumab à un traitement de première ligne combinant étoposide et sels de platine

Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study

Charles M. Rudin, Mark M. Awad, Alejandro Navarro (et al.)

PURPOSE : Pembrolizumab monotherapy has shown antitumor activity in patients with small-cell lung cancer (SCLC). The randomized, double-blind, phase III KEYNOTE-604 study compared pembrolizumab plus etoposide and platinum (EP) with placebo plus EP for patients with previously untreated extensive-stage (ES) SCLC. METHODS : Eligible patients were randomly assigned 1:1 to pembrolizumab 200 mg once every 3 weeks or saline placebo for up to 35 cycles plus 4 cycles of EP. Primary end points were [...]

Mené sur 49 patients atteints d’un cancer métastatique du poumon présentant des mutations EGFR (âge médian : 60 ans), cet essai de phase I/II évalue la dose maximale tolérée de l’osimertinib en combinaison avec le bévacizumab puis évalue l’efficacité de cette combinaison, du point de vue du taux de réponse globale et de la survie sans progression à 12 mois, en traitement de première ligne

Effect of Osimertinib and Bevacizumab on Progression-Free Survival for Patients With Metastatic EGFR-Mutant Lung Cancers : A Phase 1/2 Single-Group Open-Label Trial

Helena A. Yu, Adam J. Schoenfeld, Alex Makhnin (et al.)

Importance : The combination of erlotinib and bevacizumab as initial treatment of epidermal growth factor receptor (EGFR [OMIM 131550])–mutant lung cancers improves progression-free survival (PFS) compared with erlotinib alone. Because osimertinib prolongs PFS compared with erlotinib, this trial was designed to study the combination of osimertinib and bevacizumab as first-line treatment. Objectives : To determine the safety and tolerability of osimertinib and bevacizumab combination treatment [...]

Mené sur 365 patients atteints d’un cancer épidermoïde du poumon non à petites cellules de stade avancé ou récidivant, cet essai de phase III évalue l’efficacité, du point de vue de la survie sans progression, et la toxicité de l’ajout de S-1 aux "meilleurs soins de support" en traitement d’entretien, après une thérapie d’induction à base de S-1 et de carboplatine

A randomized phase 3 study of maintenance therapy with S-1 plus best supportive care versus best supportive care after induction therapy with carboplatin plus S-1 for advanced or relapsed squamous cell carcinoma of the lung (WJOG7512L)

Kaoru Tanaka, Satoshi Morita, Masahiko Ando(et al.)

Background : A randomized phase 3 study was performed to investigate the efficacy and safety of maintenance therapy with S?1 after induction therapy with carboplatin plus S?1 in patients with advanced squamous non–small cell lung cancer (NSCLC). Methods : Chemotherapy?naive patients with advanced or relapsed squamous NSCLC were treated with carboplatin (area under the curve of 5 on day 1 every 3 weeks) plus S?1 (40 mg/m2 twice per day on days 1?14 every 3 weeks) as induction therapy. Patients [...]

Mené sur 763 patients atteints d’un cancer du poumon non à petites cellules non épidermoïde de stade métastatique ou récidivant, cet essai de phase III compare les caractéristiques pharmacocinétiques, l’immunogénicité et l’efficacité, du point de vue du taux de réponse globale, du SB8 (un biosimilaire du bévacizumab) et du bévacizumab de référence

A phase III, randomized, double-blind, multicenter study to compare the efficacy, safety, pharmacokinetics, and immunogenicity between SB8 (proposed bevacizumab biosimilar) and reference bevacizumab in patients with metastatic or recurrent nonsquamous non-small cell lung cancer

Martin Reck, Alexander Luft, Igor Bondarenko (et al.)

Objectives : Efficacy, safety, pharmacokinetics (PK), and immunogenicity of the biosimilar candidate SB8 was compared to its reference product bevacizumab (BEV) in patients with metastatic or recurrent nonsquamous non?small cell lung cancer. Methods : Patients were randomized (1:1) in a phase III, double-blind study to receive intravenous SB8 or BEV 15?mg/kg with paclitaxel/carboplatin every 3 weeks for 24 weeks, followed by SB8 or BEV maintenance monotherapy. The primary endpoint was best [...]

Mené sur 400, 393 et 394 patients atteints d’un cancer du poumon non épidermoïde non à petites cellules, cet essai randomisé évalue l’efficacité, du point de vue de la survie sans progression et de la survie globale, et les effets indésirables rapportés par les patients, de l’ajout de l’atézolizumab à une chimiothérapie de première ligne à base de carboplatine et de paclitaxel, dispensée avec ou sans bévacizumab

Safety and Patient-Reported Outcomes of Atezolizumab Plus Chemotherapy With or Without Bevacizumab Versus Bevacizumab Plus Chemotherapy in Non–Small-Cell Lung Cancer

Martin Reck, Thomas Wehler, Francisco Orlandi (et al.)

PURPOSE : Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) demonstrated survival benefit versus bevacizumab, carboplatin, and paclitaxel (BCP) in chemotherapy-naïve nonsquamous non–small-cell lung cancer (NSCLC). We present safety and patient-reported outcomes (PROs) to provide additional information on the relative impact of adding atezolizumab to chemotherapy with and without bevacizumab in nonsquamous NSCLC. METHODS : Patients were randomly assigned to receive atezolizumab, [...]

Mené sur 152 patients atteints d’un cancer du poumon non à petites cellules présentant une mutation du gène MET (perte de l’exon 14) et de stade avancé ou métastatique, cet essai de phase II évalue l’efficacité, du point de vue du taux de réponse objective, et la toxicité du tépotinib (un inhibiteur de MET)

Tepotinib in Non–Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations

Paul K. Paik, Enriqueta Felip, Remi Veillon, Hiroshi Sakai, Alexis B. Cortot (et al.)

Background : A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driver MET occurs in 3 to 4% of patients with non–small-cell lung cancer (NSCLC). We evaluated the efficacy and safety of tepotinib, a highly selective MET inhibitor, in this patient population. Methods : In this open-label, phase 2 study, we administered tepotinib (at a dose of 500 mg) once daily in patients with advanced or metastatic NSCLC with a confirmed MET exon 14 skipping mutation. [...]

Mené sur des patients atteints d’un cancer de la prostate non métastatique et résistant à la castration, cet essai de phase III évalue l’efficacité, du point de vue de la survie globale, et la toxicité de l’ajout de l’enzalutamide à une thérapie anti-androgénique

Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer

Cora N. Sternberg, Karim Fizazi, Fred Saad (et al.)

Background : Preliminary trial results showed that enzalutamide significantly improved metastasis-free survival among men who had nonmetastatic, castration-resistant prostate cancer and rapidly increasing prostate-specific antigen (PSA) levels while taking androgen-deprivation therapy. Results from the final analysis of overall survival have not yet been reported. Methods : In this double-blind, phase 3 trial, men with nonmetastatic, castration-resistant prostate cancer (defined on the basis of [...]

Mené sur 153 patients atteints d’un cancer colorectal métastatique non résécable et inéligibles à des chimiothérapies cytotoxiques, cet essai de phase II évalue l’efficacité, du point de vue de la survie sans progression, et la toxicité de deux stratégies thérapeutiques de première ligne, la première à base de trifluridine, tipiracile et bévacizumab, la seconde combinant capécitabine et bévacizumab

Trifluridine/Tipiracil plus Bevacizumab in Patients with Untreated Metastatic Colorectal Cancer Ineligible for Intensive Therapy: the Randomized TASCO1 Study

E.Van Cutsem, I.Danielewicz, M.P.Saunders (et al.)

Purpose : We designed an open-label, non-comparative phase II study to assess the safety and efficacy of first-line treatment with trifluridine/tipiracil plus bevacizumab (TT-B) and capecitabine plus bevacizumab (C-B) in untreated patients with unresectable metastatic colorectal cancer (mCRC) who were not candidates for combination with cytotoxic chemotherapies. Patients and Methods : From 29 April 2016 to 29 March 2017, 153 patients were randomly assigned (1:1) to either TT-B (n=77) or C-B [...]

Mené sur 45 patients atteints d’un carcinome à cellules rénales de stade métastatique (âge médian : 62 ans), cet essai évalue l’efficacité, du point de vue du taux de réponse objective et de la survie sans progression, et la toxicité d’un traitement de sauvetage combinant ipilimumab et nivolumab après l’échec d’inhibiteurs de points de contrôle immunitaire

Salvage Ipilimumab and Nivolumab in Patients With Metastatic Renal Cell Carcinoma After Prior Immune Checkpoint Inhibitors

Anita Gul, Tyler F. Stewart, Charlene M. Mantia (et al.)

PURPOSE : Immune checkpoint inhibitors (ICIs) are standard therapy in metastatic renal cell carcinoma (RCC). The safety and activity of the combination of ipilimumab and nivolumab in patients who have received prior ICI targeting the programmed death 1 (PD-1) pathway remains unknown. We evaluated ipilimumab and nivolumab in patients with metastatic RCC after prior treatment with anti–PD-1 pathway–targeted therapy. PATIENTS AND METHODS : Patients with metastatic RCC who received prior anti–PD-1 [...]

Menée aux Etats-Unis à partir de données portant sur 69 patients atteints d’un carcinome à cellules rénale de stade métastatique (âge médian au diagnostic : 61 ans), cette étude de cohorte rétrospective évalue l’efficacité, du point de vue du taux de réponse globale, et la toxicité de plusieurs lignes d’immunothérapies dispensées de façon séquentielle (arrêt puis reprise)

Evaluation of the Safety and Efficacy of Immunotherapy Rechallenge in Patients With Renal Cell Carcinoma

Praful Ravi, Charlene Mantia, Christopher Su (et al.)

Importance : Several immune checkpoint inhibitors (ICIs) are approved for use in patients with metastatic renal cell carcinoma (mRCC), but the efficacy and safety of ICI rechallenge in mRCC is unknown. Objective : To evaluate the safety and efficacy of ICI rechallenge in patients with mRCC. Design, Setting, and Participants : This multicenter, retrospective cohort study included consecutive patients with mRCC from 9 institutions in the US who received at least 2 separate lines of ICI (ICI-1, [...]

Mené sur 60 patients atteints d’un carcinome papillaire à cellules rénales, cet essai de phase III compare l’efficacité, du point de vue de la survie sans progression, et la toxicité du savolitinib (un inhibiteur sélectif de MET) et du sunitinib (traitement standard)

Efficacy of Savolitinib vs Sunitinib in Patients With MET-Driven Papillary Renal Cell Carcinoma : The SAVOIR Phase 3 Randomized Clinical Trial

Toni K. Choueiri, Daniel Y. C. Heng, Jae Lyun Lee (et al.)

Importance : Papillary renal cell carcinoma (PRCC) is the most common type of non–clear cell RCC. Because some cases of PRCC are MET-driven, MET inhibition could be a targeted treatment approach. In previous studies, savolitinib (AZD6094, HMPL-504, volitinib), a highly selective MET-tyrosine kinase inhibitor, demonstrated antitumor activity in this patient group. Objective : To determine whether savolitinib is a better treatment option for this patient population, vs standard of care, [...]

Mené sur 28 patients atteints d’une tumeur hématologique récidivante (âge médian : 57 ans), cet essai de phase I évalue la dose maximale tolérée et l’efficacité, du point de vue du taux de réponse globale, du nivolumab après une greffe de cellules souches hématopoïétiques

A multicenter, phase I study of nivolumab for relapsed hematologic malignancies after allogeneic transplantation

Matthew S. Davids, Haesook T Kim, Caitlin Costello, Alex F. Herrera, Frederick L. Locke (et al.)

CTLA-4 blockade augments the graft-vs-tumor effect in relapsed hematologic malignancies (HMs) after allogeneic hematopoietic cell transplantation (alloHCT). PD-1/PDL-1 interactions also contribute to functional T cell impairment, but retrospective studies of anti-PD-1 therapy following alloHCT reported substantial toxicity from GVHD. Here, we report the results of a prospective clinical trial of PD-1 blockade for relapsed HMs after alloHCT (ClinicalTrials.gov, NCT01822509). The primary [...]

Mené sur 84 patientes atteintes d’un cancer métastatique du sein HER2-, cet essai de phase II évalue l’efficacité, du point de vue du taux de réponse objective, et la toxicité du cabazitaxel en traitement de deuxième ligne après l’échec d’un traitement à base de taxanes de première génération

Phase 2 study of cabazitaxel as second-line treatment in patients with HER2-negative metastatic breast cancer previously treated with taxanes—a Hellenic Cooperative Oncology Group (HeCOG) Trial

Angelos Koutras, Flora Zagouri, Georgia-Angeliki Koliou (et al.)

Background : Cabazitaxel is a novel taxane that might be active in breast cancer resistant to first-generation taxanes. Methods : The purpose of the current multicentre phase II trial was to evaluate the activity and safety of cabazitaxel, as second-line treatment, in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) previously treated with taxanes. The primary endpoint was objective response rate (ORR). Results : Eighty-four patients were [...]

Menée en Allemagne à partir de données portant sur 124 084 patientes atteintes d’un cancer du sein de stade précoce, cette étude analyse l’évolution, sur la période 2008-2017, de l’utilisation d’une chimiothérapie néoadjuvante

Time Trends of Neoadjuvant Chemotherapy for Early Breast Cancer

Fabian Riedel, Ann Sophie Hoffmann, Mareike Moderow (et al.)

Neoadjuvant chemotherapy (NACT) in early breast cancer (EBC) enables in vivo sensitivity testing and less radical surgery as compared to primary surgery and adjuvant chemotherapy (ACT). The aim of this study is to illustrate trends of systemic treatment of EBC. The study analyzed chemotherapy usage and time trends for patients with EBC treated at 104 German breast units between January 2008 and December 2017. The data were obtained through a quality?controlled benchmarking process. Altogether, [...]

Mené sur 291 patientes atteintes d’un cancer du sein HER2+ et présentant des métastases cérébrales, cet essai randomisé évalue l’efficacité, du point de vue du taux de réponse intracrânienne et de la survie globale, de l’ajout du tucatinib à un traitement combinant trastuzumab et capécitabine

Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial

Nancy U. Lin, Virginia Borges, Carey Anders (et al.)

PURPOSE : In the HER2CLIMB study, patients with human epidermal growth factor receptor 2 (HER2)–positive breast cancer with brain metastases (BMs) showed statistically significant improvement in progression-free survival (PFS) with tucatinib. We describe exploratory analyses of intracranial efficacy and survival in participants with BMs. PATIENTS AND METHODS : Patients were randomly assigned 2:1 to tucatinib or placebo, in combination with trastuzumab and capecitabine. All patients underwent [...]

Mené sur 66 patients atteints d’une tumeur des voies biliaires de stade localement avancé ou métastatique, cet essai de phase II évalue l’efficacité, du point de vue de la survie sans progression, du régorafénib après l’échec d’une chimiothérapie de première ligne à base de gemcitabine et de sels de platine (durée médiane de suivi : 24 mois)

Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced/metastatic biliary tumors: a randomized, double-blind, phase 2 trial – REACHIN

A.Demols, I.Borbath, M.Van den Eynde, G.Houbiers (et al.)

Background : There is a high unmet clinical need for treatments for advanced/metastatic biliary tract cancers (BTC) after progression on first-line chemotherapy. Regorafenib has demonstrated efficacy in some gastrointestinal tumors that progress on standard therapies. Patients and Methods : REACHIN was a multicenter, double-blind, placebo-controlled, randomized phase 2 study designed to evaluate the safety and efficacy of regorafenib in patients with nonresectable/metastatic BTC that progressed [...]

Mené sur 59 patients atteints d'un carcinome épidermoïde de la tête et du cou de stade III à IV, cet essai de phase I B évalue l'efficacité, du point de vue du taux de réponse complète, de la survie sans progression et de la survie globale, et la sécurité du pembrolizumab en combinaison avec une chimioradiothérapie

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study

Steven F. Powell ; Kathryn A. Gold ; Mark M. Gitau ; Christopher J. Sumey ; Michele M. Lohr ; Steven C. McGraw ; Ryan K. Nowak ; Ashley W. Jensen ; Miran J. Blanchard ; Christopher D. Fischer ; Julie Bykowski ; Christie A. Ellison ; Lora J. Black ; Paul A. Thompson ; Juan L. Callejas-Valera ; John H. Lee ; Ezra E. W. Cohen ; William C. Spanos

PURPOSE : Pembrolizumab is a humanized monoclonal antibody that blocks interaction between programmed death receptor-1 (PD-1) and its ligands (PD-L1, PD-L2). Although pembrolizumab is approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), its role in the management of locally advanced (LA) disease is not defined. We report a phase IB study evaluating the safety and efficacy of adding pembrolizumab to cisplatin-based chemoradiotherapy in patients with LA HNSCC. PATIENTS [...]

Cette étude présente l’évolution, depuis les années 1960, des stratégies thérapeutiques, de leurs effets indésirables et de la survie associée, chez des enfants atteints d’un cancer

Childhood cancer: Survival, treatment modalities, late effects and improvements over time

Friederike Erdmann, Line Elmerdahl Frederiksen, Audrey Bonaventure (et al.)

Since the 1960s, paediatric oncologists have gradually become better organised in large study groups and participation in clinical trials is today considered as the standard of care, with most children with cancer in Europe and North America being enrolled on available treatment protocols. Chemotherapy is nowadays the main element of therapy, but irradiation is still required for some patients. With the advent of multimodality therapy and supportive care, five-year cancer survival exceeds 80 % [...]

Cet article passe en revue les études concernant la prise en charge d'un glioblastome puis identifie les futurs axes de recherche

Management of glioblastoma: State of the art and future directions

Tan, Aaron C. ; Ashley, David M. ; López, Giselle Y. ; Malinzak, Michael ; Friedman, Henry S. ; Khasraw, Mustafa

Glioblastoma is the most common malignant primary brain tumor. Overall, the prognosis for patients with this disease is poor, with a median survival of <2 years. There is a slight predominance in males, and incidence increases with age. The standard approach to therapy in the newly diagnosed setting includes surgery followed by concurrent radiotherapy with temozolomide and further adjuvant temozolomide. Tumor-treating fields, delivering low-intensity alternating electric fields, can also be [...]