Menée à partir de données portant sur 1 031 patientes atteintes d'un cancer de l'ovaire de stade précoce (durée médiane de suivi : 11,9 ans), cette étude évalue, du point de vue du risque de récidive et de la survie spécifique, la sécurité d'un traitement chirurgical préservant la fertilité par rapport à un traitement chirurgical radical

Long-term results of fertility-sparing treatment compared with standard radical surgery for early-stage epithelial ovarian cancer

Fruscio, Robert ; Ceppi, Lorenzo ; Corso, Silvia ; Galli, Francesca ; Dell'Anna, Tiziana ; Dell'Orto, Federica ; Giuliani, Daniela ; Garbi, Annalisa ; Chiari, Stefania ; Mangioni, Costantino ; Milani, Rodolfo ; Floriani, Irene ; Colombo, Nicoletta ; Bonazzi, Cristina Maria

Background : The objective of this study is to evaluate the safety of fertility-sparing surgery (FSS) for early-stage epithelial ovarian cancer (EOC). Methods : A retrospective analysis was performed to identify patients treated for early-stage EOC and to compare the clinical outcomes of patients treated with FSS and radical surgery (RS). Results : A total of 1031 patients were treated at two Institutions, 242 with FSS (group A) and 789 with RS (group B). Median duration of follow-up was 11.9 [...]

A partir d'une revue systématique de la littérature (19 essais incluant au total 1 009 patients), cette méta-analyse évalue l'efficacité, du point de vue de la survie globale à 1 an, et la toxicité d'une radiothérapie corporelle stéréotaxique chez les patients atteints d'un cancer du pancréas non résécable ou à la limite de la résécabilité et de stade localement avancé

Stereotactic body radiotherapy (SBRT) for locally advanced pancreatic cancer : a systematic review and pooled analysis of 19 trials

Petrelli, Fausto ; Comito, Tiziana ; Ghidini, Antonio ; Torri, Valter ; Scorsetti, Marta ; Barni, Sandro

Introduction : While surgery is the standard of care for resectable pancreatic cancer (PC), standard dose chemoradiotherapy (CTRT) or CT alone are suitable for patients with unresectable disease. Stereotactic body radiotherapy (SBRT) is an alternative focused local therapy that delivers high RT doses in a few fractions to the cancer, sparing surrounding critical tissue. We have performed a systematic review and pooled analysis of published trials to evaluate the efficacy and safety of this [...]

A partir des données de 17 essais de phase III, cet article analyse l'intérêt d'une radiothérapie post-opératoire pour améliorer la survie globale chez les patients ayant subi une résection complète d'un cancer du poumon non à petites cellules avec envahissement des ganglions médiastinaux

Postoperative Radiotherapy for Lung Cancer : Is it worth the controversy?

Billiet, Charlotte ; Peeters, Stéphanie ; Decaluwe, Herbert ; Vansteenkiste, Johan ; Mebis, Jeroen ; Ruysscher, Dirk De

Introduction : The role of postoperative radiation therapy (PORT) in patients with completely resected non-small cell lung cancer (NSCLC) with pathologically involved mediastinal lymph nodes (N2) remains unclear. Despite a reduction of local recurrence (LR), its effect on overall survival (OS) remains unproven. Therefore we conducted a review of the current literature. Methods : To investigate the benefit and safety of modern PORT, we identified published phase III trials for PORT. We [...]

Menée à partir de données portant sur 428 patients atteints d'un adénocarcinome rectal et ayant subi entre 2005 et 2014 une exérèse totale du mésorectum par voie laparoscopique (durée moyenne de suivi : 40 mois), cette étude évalue l'effet de la survenue d'une fistule anastomotique symptomatique ou asymptomatique sur la survie sans récidive locale

Oncological impact of anastomotic leakage after laparoscopic mesorectal excision

Hain, E. ; Maggiori, L. ; Manceau, G. ; Mongin, C. ; Prost à la Denise, J. ; Panis, Y.

Background : The effect of anastomotic leakage on oncological outcomes after total mesorectal excision (TME) is controversial. This study aimed to assess the influence of symptomatic and asymptomatic anastomotic leakage on oncological outcomes after laparoscopic TME. Methods : All patients who underwent restorative laparoscopic TME for rectal adenocarcinoma with curative intent from 2005 to 2014 were identified from an institutional database. Asymptomatic anastomotic leakage was defined by CT [...]

Menée in vivo, cette étude met en évidence le rôle joué par un mécanisme de co-option vasculaire pour limiter l'efficacité d'une thérapie anti-angiogénique sur des métastases hépatiques

Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases

Frentzas, Sophia ; Simoneau, Eve ; Bridgeman, Victoria L. ; Vermeulen, Peter B. ; Foo, Shane ; Kostaras, Eleftherios ; Nathan, Mark R. ; Wotherspoon, Andrew ; Gao, Zu-hua ; Shi, Yu ; Van den Eynden, Gert ; Daley, Frances ; Peckitt, Clare ; Tan, Xianming ; Salman, Ayat ; Lazaris, Anthoula ; Gazinska, Patrycja ; Berg, Tracy J. ; Eltahir, Zak ; Ritsma, Laila ; van Rheenen, Jacco ; Khashper, Alla ; Brown, Gina ; Nyström, Hanna ; Sund, Malin ; Van Laere, Steven ; Loyer, Evelyne ; Dirix, Luc ; Cunningham, David ; Metrakos, Peter ; Reynolds, Andrew R.

The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast [...]

Menée in vitro et in vivo sur des modèles de divers types de cancers (myélome multiple, leucémie, lymphome, tumeurs solides), cette étude met en évidence l'activité antitumorale d'un composé appelé S63845, une petite molécule ciblant MCL1

The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models

Kotschy, András ; Szlavik, Zoltán ; Murray, James ; Davidson, James ; Maragno, Ana Leticia ; Le Toumelin-Braizat, Gaëtane ; Chanrion, Maia ; Kelly, Gemma L. ; Gong, Jia-Nan ; Moujalled, Donia M. ; Bruno, Alain ; Csekei, Márton ; Paczal, Attila ; Szabo, Zoltán B. ; Sipos, Szabolcs ; Radics, Gábor ; Proszenyak, Agnes ; Balint, Balázs ; Ondi, Levente ; Blasko, Gábor ; Robertson, Alan ; Surgenor, Allan ; Dokurno, Pawel ; Chen, Ijen ; Matassova, Natalia ; Smith, Julia ; Pedder, Christopher ; Graham, Christopher ; Studeny, Aurélie ; Lysiak-Auvity, Gaëlle ; Girard, Anne-Marie ; Gravé, Fabienne ; Segal, David ; Riffkin, Chris D. ; Pomilio, Giovanna ; Galbraith, Laura C. A. ; Aubrey, Brandon J. ; Brennan, Margs S. ; Herold, Marco J. ; Chang, Catherine ; Guasconi, Ghislaine ; Cauquil, Nicolas ; Melchiore, Fabien ; Guigal-Stephan, Nolwen ; Lockhart, Brian ; Colland, Frédéric ; Hickman, John A. ; Roberts, Andrew W. ; Huang, David C. S. ; Wei, Andrew H. ; Strasser, Andreas ; Lessene, Guillaume ; Geneste, Olivier

Avoidance of apoptosis is critical for the development and sustained growth of tumours. The pro-survival protein myeloid cell leukemia 1 (MCL1) is overexpressed in many cancers, but the development of small molecules targeting this protein that are amenable for clinical testing has been challenging. Here we describe S63845, a small molecule that specifically binds with high affinity to the BH3-binding groove of MCL1. Our mechanistic studies demonstrate that S63845 potently kills MCL1-dependent [...]

Cet article passe en revue les travaux récents sur les mécanismes par lesquels les cellules tumorales résistent aux traitements à base de conjugués anticorps-médicament

Mechanisms of Resistance to Antibody–Drug Conjugates

Loganzo, Frank ; Sung, Matthew ; Gerber, Hans-Peter

Drug resistance limits the effectiveness of cancer therapies. Despite attempts to develop curative anticancer treatments, tumors evolve evasive mechanisms limiting durable responses. Hence, diverse therapies are used to attack cancer, including cytotoxic and targeted agents. Antibody–drug conjugates (ADC) are biotherapeutics designed to deliver potent cytotoxins to cancer cells via tumor-specific antigens. Little is known about the clinical manifestations of drug resistance to this class of [...]

Menée à l'aide de modèles murins présentant de grosses tumeurs solides, cette étude met en évidence l'activité antitumorale d'un traitement combinant 4 immunothérapies

Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses

Moynihan, Kelly D. ; Opel, Cary F. ; Szeto, Gregory L. ; Tzeng, Alice ; Zhu, Eric F. ; Engreitz, Jesse M. ; Williams, Robert T. ; Rakhra, Kavya ; Zhang, Michael H. ; Rothschilds, Adrienne M. ; Kumari, Sudha ; Kelly, Ryan L. ; Kwan, Byron H. ; Abraham, Wuhbet ; Hu, Kevin ; Mehta, Naveen K. ; Kauke, Monique J. ; Suh, Heikyung ; Cochran, Jennifer R. ; Lauffenburger, Douglas A. ; Wittrup, K. Dane ; Irvine, Darrell J.

Checkpoint blockade with antibodies specific for cytotoxic T lymphocyte-associated protein (CTLA)-4 or programmed cell death 1 (PDCD1; also known as PD-1) elicits durable tumor regression in metastatic cancer, but these dramatic responses are confined to a minority of patients. This suboptimal outcome is probably due in part to the complex network of immunosuppressive pathways present in advanced tumors, which are unlikely to be overcome by intervention at a single signaling checkpoint. Here we [...]

Menée à l'aide de modèles murins, cette étude met en évidence des mécanismes épigénétiques permettant de rendre compte de l'efficacité limitée des immunothérapies anti PD-L1

Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade

Pauken, Kristen E. ; Sammons, Morgan A. ; Odorizzi, Pamela M. ; Manne, Sasikanth ; Godec, Jernej ; Khan, Omar ; Drake, Adam M. ; Chen, Zeyu ; Sen, Debattama ; Kurachi, Makoto ; Barnitz, R. Anthony ; Bartman, Caroline ; Bengsch, Bertram ; Huang, Alexander C. ; Schenkel, Jason M. ; Vahedi, Golnaz ; Haining, W. Nicholas ; Berger, Shelley L. ; Wherry, E. John

Blocking PD-1 can re-invigorate exhausted CD8 T cells (TEX) and improve control of chronic infections and cancer. However, whether blocking PD-1 can reprogram TEX into durable memory T cells (TMEM) is unclear. We found that re-invigoration of TEX in mice by PD-L1 blockade caused minimal memory development. After blockade, re-invigorated TEX became re-exhausted if antigen remained high, and failed to become TMEM upon antigen clearance. TEX acquired an epigenetic profile distinct from effector [...]

Cet article passe en revue les perspectives offertes par le développement d'immunothérapies pour le traitement des patients atteints d'un myélome multiple

New Strategies in Multiple Myeloma: Immunotherapy as a Novel Approach to Treat Patients with Multiple Myeloma

Neri, Paola ; Bahlis, Nizar J. ; Lonial, Sagar

Multiple Myeloma (MM) is a B-cell malignancy characterized by proliferation of monoclonal plasma cells in the bone marrow. Although new therapeutic options introduced in recent years have resulted in improved survival outcomes, MM still remains incurable for a large number of patients and new treatment options are urgently needed. Over the last 5 years there has been a renewed interest in the clinical potential of immunotherapy for the treatment of MM. Clinical progression of myeloma is known [...]

Menée in vitro et in vivo sur des modèles de cancer colorectal, cette étude met en évidence des mécanismes par lesquels un composé appelé TASIN-1 détruit de façon sélective les cellules cancéreuses présentant un gène APC muté

Selective targeting of mutant adenomatous polyposis coli (APC) in colorectal cancer

Zhang, Lu ; Theodoropoulos, Panayotis C. ; Eskiocak, Ugur ; Wang, Wentian ; Moon, Young-Ah ; Posner, Bruce ; Williams, Noelle S. ; Wright, Woodring E. ; Kim, Sang Bum ; Nijhawan, Deepak ; De Brabander, Jef K. ; Shay, Jerry W.

The adenomatous polyposis gene (APC), which is a tumor suppressor, is commonly mutated in colon cancer and cannot be directly targeted by existing therapeutics. Zhang et al. identified a drug called TASIN-1, which specifically targets cells with APC truncations, the most common APC mutation seen in colorectal cancer. The authors showed that this drug interferes with cholesterol biosynthesis and that it selectively kills APC-truncated cancer cells in vitro and in mouse models without any [...]

A partir de données portant sur des patientes atteintes d'un cancer du sein triplement négatif, puis menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude met en évidence des mécanismes suggérant l'intérêt d'un traitement à base d'inhibiteur du proto-oncogène PIM1 pour sensibiliser les cellules cancéreuses à une chimiothérapie

PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer

Braso-Maristany, Fara ; Filosto, Simone ; Catchpole, Steven ; Marlow, Rebecca ; Quist, Jelmar ; Francesch-Domenech, Erika ; Plumb, Darren A. ; Zakka, Leila ; Gazinska, Patrycja ; Liccardi, Gianmaria ; Meier, Pascal ; Gris-Oliver, Albert ; Cheang, Maggie Chon U. ; Perdrix-Rosell, Anna ; Shafat, Manar ; Noel, Elodie ; Patel, Nirmesh ; McEachern, Kristen ; Scaltriti, Maurizio ; Castel, Pau ; Noor, Farzana ; Buus, Richard ; Mathew, Sumi ; Watkins, Johnathan ; Serra, Violeta ; Marra, Pierfrancesco ; Grigoriadis, Anita ; Tutt, Andrew N.

Triple-negative breast cancers (TNBCs) have poor prognosis and lack targeted therapies. Here we identified increased copy number and expression of the PIM1 proto-oncogene in genomic data sets of patients with TNBC. TNBC cells, but not nonmalignant mammary epithelial cells, were dependent on PIM1 for proliferation and protection from apoptosis. PIM1 knockdown reduced expression of the anti-apoptotic factor BCL2, and dynamic BH3 profiling of apoptotic priming revealed that PIM1 prevents [...]

Menée à l'aide de xénogreffes dérivées de tumeurs prélevées sur des patientes atteintes d'un cancer du sein triplement négatif, puis à l'aide de modèles murins transgéniques, cette étude suggère l'intérêt d'un traitement à base d'inhibiteurs de PIM1 pour les patientes dont les tumeurs surexpriment le facteur de transcription MYC

PIM1 kinase inhibition as a targeted therapy against triple-negative breast tumors with elevated MYC expression

Horiuchi, Dai ; Camarda, Roman ; Zhou, Alicia Y. ; Yau, Christina ; Momcilovic, Olga ; Balakrishnan, Sanjeev ; Corella, Alexandra N. ; Eyob, Henok ; Kessenbrock, Kai ; Lawson, Devon A. ; Marsh, Lindsey A. ; Anderton, Brittany N. ; Rohrberg, Julia ; Kunder, Ratika ; Bazarov, Alexey V. ; Yaswen, Paul ; McManus, Michael T. ; Rugo, Hope S. ; Werb, Zena ; Goga, Andrei

Triple-negative breast cancer (TNBC), in which cells lack expression of the estrogen receptor (ER), the progesterone receptor (PR) and the ERBB2 (also known as HER2) receptor, is the breast cancer subtype with the poorest outcome. No targeted therapy is available against this subtype of cancer owing to a lack of validated molecular targets. We previously reported that signaling involving MYC—an essential, pleiotropic transcription factor that regulates the expression of hundreds of genes—is [...]

A partir de 72 échantillons tumoraux prélevés -avant et après une chimiothérapie- sur des patients atteints d'un carcinome urothélial, cette étude analyse l'évolution clonale en réponse au traitement

Clonal evolution of chemotherapy-resistant urothelial carcinoma

Faltas, Bishoy M. ; Prandi, Davide ; Tagawa, Scott T. ; Molina, Ana M. ; Nanus, David M. ; Sternberg, Cora ; Rosenberg, Jonathan ; Mosquera, Juan Miguel ; Robinson, Brian ; Elemento, Olivier ; Sboner, Andrea ; Beltran, Himisha ; Demichelis, Francesca ; Rubin, Mark A.

Chemotherapy-resistant urothelial carcinoma has no uniformly curative therapy. Understanding how selective pressure from chemotherapy directs the evolution of urothelial carcinoma and shapes its clonal architecture is a central biological question with clinical implications. To address this question, we performed whole-exome sequencing and clonality analysis of 72 urothelial carcinoma samples, including 16 matched sets of primary and advanced tumors prospectively collected before and after [...]

Mené sur 168 patients atteints d'un adénocarcinome avancé de l'œsophage ou de la jonction œso-gastrique, cet essai randomisé de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du ramucirumab en complément d'une chimiothérapie mFOLFOX6

Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: a randomized, double-blind, multicenter Phase II trial

Yoon, H. H. ; Bendell, J. C. ; Braiteh, F. S. ; Firdaus, I. ; Philip, P. A. ; Cohn, A. L. ; Lewis, N. ; Anderson, D. M. ; Arrowsmith, E. ; Schwartz, J. D. ; Gao, L. ; Hsu, Y. ; Xu, Y. ; Ferry, D. ; Alberts, S. R. ; Wainberg, Z. A.

Background We report the first randomized, Phase II trial of ramucirumab, an anti-vascular endothelial growth factor receptor-2 monoclonal antibody, as front-line therapy in patients with advanced adenocarcinoma of the esophagus or gastric/gastroesophageal junction (GEJ). Patients and methods Patients from the USA with advanced esophageal, gastric, or GEJ adenocarcinoma randomly received (1:1) mFOLFOX6 plus ramucirumab (8 mg/kg) or mFOLFOX6 plus placebo every 2 weeks. The primary end point was [...]

A partir d'une revue systématique de la littérature publiée jusqu'en février 2016 sur des essais randomisés de phase III ayant évalué un traitement à base de sorafénib (au total, 6 797 patients atteints d'une tumeur solide), cette méta-analyse évalue les risques d'événements indésirables, sévères ou fatals, associés au sorafénib

Risk of Serious Adverse Events and Fatal Adverse Events with Sorafenib in Patients with Solid Cancer: A meta-analysis of phase 3 Randomized Controlled Trials

Gyawali, B. ; Shimokata, T. ; Ando, M. ; Honda, K. ; Ando, Y.

Background: Sorafenib is a multikinase-tyrosine kinase inhibitor commonly used in a variety of cancers. There are concerns about the increased risk of serious adverse events (SAEs) and fatal adverse events (FAEs) with sorafenib. We performed an up-to-date meta-analysis of all phase 3 randomized controlled trials (RCTs) of sorafenib to quantify the increased risk of SAEs and FAEs. Patients and Methods: We carried out a systematic search of electronic databases for studies published from [...]

Mené sur 132 patients atteints d'une tumeur solide ou d'un lymphome de stade avancé, cet essai de phase I analyse les caractéristiques pharmacocinétiques et pharmocodynamiques, l'activité antitumorale et la dose maximale tolérée du ribociclib

A Phase I Study of the Cyclin-Dependent Kinase 4/6 Inhibitor Ribociclib (LEE011) in Patients with Advanced Solid Tumors and Lymphomas

Infante, Jeffrey R. ; Cassier, Philippe A. ; Gerecitano, John F. ; Witteveen, Petronella O. ; Chugh, Rashmi ; Ribrag, Vincent ; Chakraborty, Abhijit ; Matano, Alessandro ; Dobson, Jason R. ; Crystal, Adam S. ; Parasuraman, Sudha ; Shapiro, Geoffrey I.

Purpose: Ribociclib (an oral, highly specific cyclin-dependent kinase 4/6 inhibitor) inhibits tumor growth in preclinical models with intact retinoblastoma protein (Rb+). This first-in-human study investigated the MTD, recommended dose for expansion (RDE), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of ribociclib in patients with Rb+ advanced solid tumors or lymphomas. Experimental Design: Patients received escalating doses of ribociclib (3-weeks-on/1-week-off or [...]

Mené en France sur 330 patients atteints d'une leucémie myéloïde aiguë après 60 ans, cet essai multicentrique de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de la noréthandrolone en traitement d'entretien

Addition of Androgens Improves Survival in Elderly Patients With Acute Myeloid Leukemia: A GOELAMS Study

Pigneux, Arnaud ; Béné, Marie C. ; Guardiola, Philippe ; Recher, Christian ; Hamel, Jean-Francois ; Sauvezie, Mathieu ; Harousseau, Jean-Luc ; Tournilhac, Olivier ; Witz, Francis ; Berthou, Christian ; Escoffre-Barbe, Martine ; Guyotat, Denis ; Fegueux, Nathalie ; Himberlin, Chantal ; Hunault, Mathilde ; Delain, Martine ; Lioure, Bruno ; Jourdan, Eric ; Bauduer, Frederic ; Dreyfus, François ; Cahn, Jean-Yves ; Sotto, Jean-Jacques ; Ifrah, Norbert

Purpose Elderly patients with acute myeloid leukemia (AML) have a poor prognosis, and innovative maintenance therapy could improve their outcomes. Androgens, used in the treatment of aplastic anemia, have been reported to block proliferation of and initiate differentiation in AML cells. We report the results of a multicenter, phase III, randomized open-label trial exploring the benefit of adding androgens to maintenance therapy in patients 60 years of age or older. Patients and Methods A total [...]

Cet article analyse les bénéfices et les risques associés aux divers inhibiteurs de tyrosine kinase autorisés pour le traitement des patients atteints d'une leucémie myéloïde chronique

Tyrosine kinase inhibitors in chronic myeloid leukaemia: which, when, for whom?

Rosti, Gianantonio ; Castagnetti, Fausto ; Gugliotta, Gabriele ; Baccarani, Michele

The therapeutic armamentarium for chronic myeloid leukaemia (CML) comprises mainly tyrosine kinase inhibitors (TKIs), with several agents available for frontline treatment, or for the treatment of disease resistance or intolerance to the first-choice or second-choice drug. The availability of different drugs is a major achievement, but means that choices must be made [mdash] which can be difficult and questionable at times. The most important end point considered in decision-making regarding [...]

Mené au Japon sur 24 patients atteints d'un cancer du poumon non à petites cellules de stade avancé, cet essai de phase Ib évalue la toxicité et l'activité antitumorale du nivolumab en combinaison avec une chimiothérapie

Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study

Kanda, S. ; Goto, K. ; Shiraishi, H. ; Kubo, E. ; Tanaka, A. ; Utsumi, H. ; Sunami, K. ; Kitazono, S. ; Mizugaki, H. ; Horinouchi, H. ; Fujiwara, Y. ; Nokihara, H. ; Yamamoto, N. ; Hozumi, H. ; Tamura, T.

Background The human IgG4 monoclonal antibody nivolumab targets programmed cell death-1 (PD-1) and promotes antitumor response by blocking the interaction of PD-1 with its ligands. This single-center phase Ib study investigated the tolerability, safety, and pharmacokinetics of nivolumab combined with standard chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods Patients who had stage IIIB without indication for definitive radiotherapy, stage IV, or [...]

A partir d'une revue des essais randomisés incluant un total de 7 997 patients atteints d'un cancer du poumon non à petites cellules (15 essais), cette méta-analyse évalue l'efficacité, du point de vue de la survie globale et de la survie sans progression, et la toxicité de l'ajout de thérapies ciblées anti-angiogéniques à une chimiothérapie

The addition of anti-angiogenic tyrosine kinase inhibitors to chemotherapy for patients with advanced non-small-cell lung cancers: A meta-analysis of randomized trials

Li, Bob T. ; Barnes, Tristan A. ; Chan, David L. ; Naidoo, Jarushka ; Lee, Adrian ; Khasraw, Mustafa ; Marx, Gavin M. ; Kris, Mark G. ; Clarke, Stephen J. ; Drilon, Alexander ; Rudin, Charles M. ; Pavlakis, Nick

Objectives : The role of anti-angiogenic tyrosine kinase inhibitors (AATKI) for patients with non-small-cell lung cancers (NSCLC) is uncertain. We conducted a comprehensive meta-analysis to assess the overall utility of adding AATKI to chemotherapy. Materials and Methods : We included 15 randomized controlled trials (RCTs) of AATKI plus chemotherapy versus chemotherapy involving 7997 patients with advanced NSCLC. Meta-analysis was performed to obtain pooled hazard ratios (HR) for OS and PFS, [...]

Mené sur 372 patients atteints d'un cancer colorectal métastatique ou réfractaire présentant un gène KRAS non muté, cet essai de phase III évalue l'efficacité, du point de vie de la suvie globale, de l'ajout du panitumumab aux soins de support

A phase 3 trial evaluating panitumumab plus best supportive care vs best supportive care in chemorefractory wild-type KRAS or RAS metastatic colorectal cancer

Kim, Tae Won ; Elme, Anneli ; Kusic, Zvonko ; Park, Joon Oh ; Udrea, Anghel Adrian ; Kim, Sun Young ; Ahn, Joong Bae ; Valencia, Ricardo Villalobos ; Krishnan, Srinivasan ; Bilic, Ante ; Manojlovic, Nebojsa ; Dong, Jun ; Guan, Xuesong ; Lofton-Day, Catherine ; Jung, A. Scott ; Vrdoljak, Eduard

Background: We assessed the treatment effect of panitumumab plus best supportive care (BSC) vs BSC on overall survival (OS) in patients with chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer (mCRC) and report the first prospective extended RAS analysis in a phase 3 trial. Methods: Patients with wild-type KRAS exon 2 mCRC were randomised 1 : 1 to panitumumab (6 mg kg−1 Q2W) plus BSC or BSC. On-study crossover was prohibited. RAS mutation status was determined by central [...]

Mené sur 69 patients atteints d'un cancer colorectal présentant une mutation du gène KRAS, cet essai de phase II/III évalue l'efficacité, du point de vue du taux de réponse objective et de la survie sans progression, et la toxicité de l'ajout du dalotuzumab à un traitement combinant irinotécan et cétuximab

Dalotuzumab in chemorefractory KRAS exon 2 mutant colorectal cancer: Results from a randomised phase II/III trial

Sclafani, Francesco ; Kim, Tae Y. ; Cunningham, David ; Kim, Tae W. ; Tabernero, Josep ; Schmoll, Hans J. ; Roh, Jae K. ; Kim, Sun Y. ; Park, Young S. ; Guren, Tormod K. ; Hawkes, Eliza ; Clarke, Stephen J. ; Ferry, David ; Frödin, Jan-Erik ; Ayers, Mark ; Nebozhyn, Michael ; Peckitt, Clare ; Loboda, Andrey ; Watkins, David J.

Limited data are available on the efficacy of anti-IGF-1R agents in KRAS mutant colorectal cancer (CRC). We analysed the outcome of 69 chemorefractory, KRAS exon 2 mutant CRC patients who were enrolled in a double-blind, randomised, phase II/III study of irinotecan and cetuximab plus dalotuzumab 10 mg/kg once weekly (arm A), dalotuzumab 7.5 mg/kg every second week (arm B) or placebo (arm C). Objective response rate (5.6% vs. 3.1% vs. 4.8%), median progression-free survival (2.7 vs. 2.6 vs. 1.4 [...]

Menée en Italie à partir de données portant sur 23 patients masculins atteints d'un cancer du sein (âge médian : 64 ans), cette étude multicentrique évalue l'efficacité, du point de vue de la survie globale, et la toxicité de l'éribuline

Eribulin in Male Patients With Breast Cancer: The First Report of Clinical Outcomes

Giotta, Francesco ; Acito, Luigi ; Candeloro, Giampiero ; Del Medico, Pietro ; Gadaleta-Caldarola, Gennaro ; Giordano, Guido ; Gueli, Rossana ; Lugini, Antonio ; Magri, Valentina ; Mandarà, Marta ; Masci, Giovanna ; Pisconti, Salvatore ; Pistelli, Mirco ; Rizzi, Anna ; Salesi, Nello ; Schirone, Alessio ; Scognamiglio, Giovanni ; Tedeschi, Maria ; Zucchinelli, Patrizia

Evidence on the management and treatment of male breast cancer is scant. We report the analysis of a multicenter Italian series of patients with male breast cancer treated with eribulin. To our knowledge, this is the first report on the use or eribulin in this setting.Patients were retrospectively identified in 19 reference centers. All patients received eribulin treatment, according to the standard practice of each center. Data on the identified patients were collected using a standardized [...]

Mené sur 25 patientes atteintes d'un cancer du sein HER2 négatif et présentant des métastases osseuses, cet essai de phase I/II évalue l'efficacité, du point de vue du taux de réponse objective, la dose recommandée et la toxicité du dasatinib dispensé par voie orale et combiné à de l'acide zolédronique

TBCRC-010: Phase I/II Study of Dasatinib in Combination with Zoledronic Acid for the Treatment of Breast Cancer Bone Metastasis

Mitri, Zahi ; Nanda, Rita ; Blackwell, Kimberly ; Costelloe, Colleen M. ; Hood, Ilona ; Wei, Caimiao ; Brewster, Abenaa M. ; Ibrahim, Nuhad K. ; Koenig, Kimberly B. ; Hortobagyi, Gabriel N. ; Van Poznak, Catherine ; Rimawi, Mothaffar F. ; Moulder-Thompson, Stacy

Purpose: Osteoclast-mediated bone resorption through src kinase releases growth factors, sustaining bone metastases. This trial determined the recommended phase II dose (RP2D) and clinical efficacy of the src kinase inhibitor dasatinib combined with zoledronic acid in bone predominant, HER2-negative breast cancer metastases. Experimental Design: A 3+3 lead in phase I design confirmed the RP2D allowing activation of the single-arm, phase II trial. Zoledronic acid was administered intravenously [...]

Mené sur 35 patients présentant une ou plusieurs métastases au niveau du foie ou des poumons, cet essai de phase I évalue la dose limitante toxique de l'ipilimumab en combinaison avec une radiothérapie stéréotaxique ablative, puis analyse la réponse antitumorale des cellules du système immunitaire

Ipilimumab with stereotactic ablative radiation therapy : Phase I results and immunologic correlates from peripheral T-cells

Tang, Chad ; Welsh, James W. ; de Groot, Patricia ; Massarelli, Erminia ; Chang, Joe Y. ; Hess, Kenneth R. ; Basu, Sreyashi ; Curran, Michael A ; Cabanillas, Maria E ; Subbiah, Vivek ; Fu, Siqing ; Tsimberidou, Apostolia M. ; Karp, Daniel ; Gomez, Daniel R ; Diab, Adi ; Komaki, Ritsuko ; Heymach, John V ; Sharma, Padmanee ; Naing, Aung ; Hong, David S.

Purpose : Little prospective data is available on clinical outcomes and immune correlates from combination radiation and immunotherapy. We conducted a phase I trial (NCT02239900) testing stereotactic ablative radiation therapy (SABR) with ipilimumab. Experimental Design : SABR was given either concurrently (1 day after the first dose) or sequentially (1 week after the second dose) with ipilimumab (3 mg/kg every 3 weeks for 4 doses) to 5 treatment groups: concurrent 50 Gy (in 4 fractions) to [...]

Menée à partir de données portant sur 608 patients atteints d'un adénocarcinome de l'œsophage ou de la jonction gastro-œsophagienne de stade II ou III et traités par résection entre 2001 et 2012, cette étude multicentrique compare, du point de vue de la survie globale à 3 ans, l'intérêt d'ajouter une radiothérapie à une chimiothérapie néoadjuvante

Multimodality treatment for esophageal adenocarcinoma : multi-center propensity-score matched study

Markar, S.R. ; Noordman, B.J. ; Mackenzie, H. ; Findlay, J.M. ; Boshier, P.R. ; Ni, M. ; Steyerberg, E.W. ; Van der Gaast, A. ; Hulshof, M.C.C.M. ; Maynard, N. ; van Berge Henegouwen, M.I. ; Wijnhoven, B.P.L. ; Reynolds, J.V. ; van Lanschot, J. Jan B. ; Hanna, G.B.

Background : The primary aim of this study was to compare survival from neoadjuvant chemoradiotherapy plus surgery (NCRS) versus neoadjuvant chemotherapy plus surgery (NCS) for the treatment of esophageal or junctional adenocarcinoma. The secondary aims were to compare pathological effects, short-term mortality and morbidity, and to evaluate the effect of lymph node harvest upon survival in both treatment groups. Methods : Data were collected from 10 European centres from 2001–2012. 608 [...]

Mené sur 18 patients atteints d'un cancer de la prostate avec récidive biochimique après une prostatectomie radicale, cet essai de phase I évalue la dose limitante toxique et la tolérabilité de l'évérolimus en combinaison avec une radiothérapie fractionnée dans le cadre d'un traitement de sauvetage

Phase I Trial of Everolimus and Radiation Therapy for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients Following Prostatectomy

Narayan, Vivek ; Vapiwala, Neha ; Mick, Rosemarie ; Subramanian, Pearl ; Christodouleas, John P. ; Bekelman, Justin E. ; Deville, Curtiland ; Rajendran, Ramji ; Haas, Naomi B.

Background : Up to half of patients treated with salvage radiation therapy (SRT) for rising PSA ultimately develop a second biochemical recurrence (sBCR). Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin (mTOR) pathway can lead to tumor hypoxia and radioresistance. Everolimus is an mTOR inhibitor with both anti-tumor and radiosensitizing effects. Methods : We performed a phase I study using a modified [...]

Menée aux Etats-Unis à partir des données 2004-2008 du registre national des cancers et d'un registre hospitalier portant sur 15 810 patients atteints d'un adénocarcinome rectal de stade II ou III, cette étude analyse, en fonction du traitement reçu (chimioradiothérapie en combinaison ou non avec une intervention chirurgicale), la survie globale à long terme des patients

Long-term survival after chemoradiotherapy without surgery for rectal adenocarcinoma : A word of caution

Ellis, C. ; Dusetzina, S. B. ; Sanoff, H. ; Stitzenberg, K. B.

Early studies with small samples from specialized centers report success with nonoperative management (NOM) or the watch-and-wait approach after neoadjuvant chemoradiotherapy for rectal adenocarcinoma. However, it is unknown whether the results are generalizable to the broader population of patients with rectal cancer. Still, use of chemoradiotherapy without surgery has doubled among individuals with nonmetastatic rectal adenocarcinoma. The highest use is observed among those who typically have [...]

Menée sur des lignées cellulaires de cancer colorectal et à l'aide de xénogreffes sur des modèles murins, cette étude montre que CRLX101, une nanoparticule contenant de la camptothécine, améliore l'efficacité d'une chimioradiothérapie en inhibant la réparation de l'ADN et la voie d'activation du facteur HIF-1alpha

CRLX101, a nanoparticle-drug conjugate containing camptothecin, improves rectal cancer chemoradiotherapy by inhibiting DNA repair and HIF-1alpha

Tian, Xi ; Nguyen, Minh ; Foote, Henry Putnam ; Caster, Joseph M ; Roche, Kyle C ; Peters, Christian G ; Wu, Pauline ; Jayaraman, Lata ; Garmey, Edward G. ; Tepper, Joel E ; Eliasof, Scott ; Wang, Andrew Z

Novel agents are needed to improve chemoradiotherapy for locally advanced rectal cancer. In this study, we assessed the ability of CRLX101, an investigational nanoparticle-drug conjugate containing the payload camptothecin (CPT), to improve therapeutic responses as compared to standard chemotherapy. CRLX101 was evaluated as a radiosensitizer in colorectal cancer cell lines and murine xenograft models. CRLX101 was as potent as CPT in vitro in its ability to radiosensitize cancer cells. [...]

A partir de données portant sur 277 essais cliniques randomisés (publiés entre 2011 et 2015) pour le traitement d'un cancer du sein, du poumon non à petites cellules, du côlon-rectum ou du pancréas, cette étude analyse leurs résultats au regard des seuils de bénéfice clinique significatif définis par l'European Society for Medical Oncology

Do Contemporary Randomized Controlled Trials Meet ESMO Thresholds for Meaningful Clinical Benefit?

Del Paggio, J.C. ; Azariah, B. ; Sullivan, R. ; Hopman, W.M. ; James, F.V. ; Roshni, S. ; Tannock, I.F. ; Booth, C.M.

Background: The European Society for Medical Oncology (ESMO) recently released a magnitude of clinical benefit scale (ESMO-MCBS) for systemic therapies for solid cancers. Here, we evaluate contemporary randomized controlled trials (RCTs) against the proposed ESMO thresholds for meaningful clinical benefit. Methods: RCTs evaluating systemic therapy for breast cancer, non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic cancer published 2011–2015 were reviewed. Data were [...]

Menée à l'aide d'un modèle de Markov basé sur les résultats d'un essai canadien incluant 190 patients atteints d'un sarcome des tissus mous des extrémités, cette étude analyse le rapport coût-efficacité d'une radiothérapie post-opératoire par rapport à une radiothérapie pré-opératoire

Cost-effectiveness Analysis of Preoperative Versus Postoperative Radiotherapy in Extremity Soft Tissue Sarcoma

Qu, Xuanlu ; Louie, Alexander V. ; Ashman, Jonathan ; Wasif, Nabil

Purpose : Surgery combined with radiotherapy (RT) is the cornerstone of multi-disciplinary management of extremity soft tissue sarcoma (STS). Although RT can be given in either the preoperative or postoperative setting with similar local recurrence and survival outcomes, side effect profiles, costs and long-term functional outcomes are different. The aim of this study is to use decision analysis to determine optimal sequencing of RT with surgery in patients with extremity STS. Methods and [...]