25 results on '"Marinela Augustin"'
Search Results
2. Preinfection laboratory parameters may predict COVID‐19 severity in tumor patients
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Alexander Kiani, Romina Roesch, Clemens M. Wendtner, Frank Kullmann, Thomas Kubin, Thomas Südhoff, Marinela Augustin, Markus Schaich, Clemens Müller‐Naendrup, Gerald Illerhaus, Frank Hartmann, Holger Hebart, Ruth Seggewiss‐Bernhardt, Martin Bentz, Ernst Späth‐Schwalbe, Peter Reimer, Ulrich Kaiser, Markus Kapp, Ullrich Graeven, Jens‐Marcus Chemnitz, Jörg Baesecke, Helmut Lambertz, and Ralph Naumann
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biomarkers ,cancer ,COVID‐19 ,neutrophils ,SARS‐CoV‐2 ,tumor ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Infection with SARS‐CoV‐2 leads to COVID‐19, the course of which is highly variable and depends on numerous patient‐specific risk factors. Patients with tumor diseases are considered to be more susceptible to severe COVID‐19; however, they also represent a heterogeneous group of individuals with variable risk. Identifying specific risk factors for a severe course of COVID‐19 in patients with cancer is of great importance. Methods Patients diagnosed with solid tumors or hematological malignancies and PCR‐confirmed SARS‐CoV‐2 infection were included into the multicentric ADHOK (Arbeitsgemeinschaft der Hämatologen und Onkologen im Krankenhaus e.V.) coronavirus tumor registry. Detailed information about the patients’ cancer disease, treatment, and laboratory parameters prior to infection, was collected retrospectively. The outcome of the SARS‐CoV‐2 infection was graded according to the WHO. Results A total of 195 patients (68% with solid neoplasms and 32% with hematological malignancies) were included in the registry. Overall, the course of the SARS‐CoV‐2 infection varied greatly, as 69% of all patients were either asymptomatic or encountered a mild to moderate course, while 23% of the cohort died from COVID‐19. In multivariable analysis, preinfection laboratory parameters (determined at least 10 days and a median of 21 days before the first documentation of SARS‐CoV‐2 infection) significantly correlated with severe course of the disease. Out of these, the absolute neutrophil count prior to infection showed the strongest association with COVID‐19‐related death. Conclusion The course of COVID‐19 in patients with tumor diseases is highly variable. Preinfection laboratory parameters may aid to identify patients at risk for severe COVID‐19 at an early stage prior to infection with the virus. German Clinical Trials Register identification: DRKS00023012.
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- 2021
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3. Long-term outcomes from the phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma
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Johannes Duell, Kami J. Maddocks, Eva González-Barca, Wojciech Jurczak, Anna Marina Liberati, Sven de Vos, Zsolt Nagy, Aleš Obr, Gianluca Gaidano, Pau Abrisqueta, Nagesh Kalakonda, Marc André, Martin Dreyling, Tobias Menne, Olivier Tournilhac, Marinela Augustin, Andreas Rosenwald, Maren Dirnberger-Hertweck, Johannes Weirather, Sumeet Ambarkhane, and Gilles Salles
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Not available.
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- 2021
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4. Community-driven development of a modified progression-free survival ratio for precision oncology
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Sebastian Schölch, Benedikt Brors, Albrecht Stenzinger, Ursula Ehmer, Ulrich-Frank Pape, Christoph Springfeld, Dirk Jäger, Felix J Hüttner, Andreas Mock, Christoph E Heilig, Simon Kreutzfeldt, Daniel Huebschmann, Christoph Heining, Evelin Schröck, Richard Schlenk, Hanno Glimm, Stefan Fröhling, Peter Horak, Leonidas Apostolidis, Marinela Augustin, Daniela Aust, Irfan Ahmed Bhatti, Johannes Bloehdorn, Cornelia Brendel, Christian Britschgi, Jan Braess, Stefan Burdach, Elena Busch, Jozefina Casuscelli, Alexander Desuki, Thomas Deutsch, Mareike Dietrich, Thomas J Ettrich, Johanna Falkenhorst, Tanja Fehm, Anne Flörcken, Andrea Forschner, Stefan Fuxius, Maria Gonzales-Carmona, Frank Griesinger, Sabine Grill, Stefan Gröschel, Georg Martin Haag, Ulrich Haag, Niels Halama, Holger Hebart, Nina Heidger, Barbara Hermes, Georg Hess, Simone Hettmer, Manuela Hoechstetter, Martin Hoffmann, Anna L Illert, Maximilian Jenzer, Bernd Kasper, Stefan Kasper-Virchow, Thomas Kindler, Ewa Koscielniak, Jan Krönke, Michael Kühn, Volker Kunzmann, Alois Lang, Jonas Leichsenring, Elisabeth Livingstone, Lucia Liotta, Kim Luley, Elisabeth Mack, Uwe M Martens, Klaus Metzeler, Jan Moritz Middeke, Lino Möhrmann, Roopa Jayarama-Naidu, Lukas Perkhofer, Arne Pfeufer, Constantin Pixberg, Michael Quante, Bernhard Rendenbach, Damian Rieke, Christian Rothermundt, Andre Norbert Sagerer, Martin Salzmann, Dieter Saur, Bastian Schilling, Jan Schleicher, Anke Schlenska-Lange, Thomas Schmidt, Sophia Schmitz, Rajiv Shah, Khalid Shoumariyeh, Alexander Siebenhüner, Martin Singh, Jens Siveke, Helen Starke, Sophia Strobel, Veronica Teleanu, Niklas Thon, Sebastian Wagner, Thomas Walle, Benedikt Westphalen, Bettina Whitlock, Eva Winkler, Naita Maren Wirsik, Lena Woydack, Angelika Zabel-du Bois, and Stefanie Zschäbitz
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Objective Measuring the success of molecularly guided therapies is a major challenge in precision oncology trials. A commonly used endpoint is an intra-patient progression-free survival (PFS) ratio, defined as the PFS interval associated with molecularly guided therapy (PFS2) divided by the PFS interval associated with the last prior systemic therapy (PFS1), above 1.3 or, in some studies, above 1.33 or 1.5.Methods To investigate if the concept of PFS ratios is in agreement with actual response evaluations by physicians, we conducted a survey among members of the MASTER (Molecularly Aided Stratification for Tumor Eradication Research) Programme of the German Cancer Consortium who were asked to classify the success of molecularly guided therapies in 194 patients enrolled in the MOSCATO 01 trial based on PFS1 and PFS2 times.Results A comparison of classification profiles revealed three distinct clusters of PFS benefit assessments. Only 29% of assessments were consistent with a PFS ratio threshold of 1.3, whereas the remaining 71% of participants applied a different classification scheme that did not rely on the relation between PFS times alone, but also took into account absolute PFS1 intervals. Based on these community-driven insights, we developed a modified PFS ratio that incorporates the influence of absolute PFS1 intervals on the judgement of clinical benefit by physicians. Application of the modified PFS ratio to outcome data from two recent precision oncology trials, MOSCATO 01 and WINTHER, revealed significantly improved concordance with physician-perceived clinical benefit and identified comparable proportions of patients who benefited from molecularly guided therapies.Conclusions The modified PFS ratio may represent a meaningful clinical endpoint that could aid in the design and interpretation of future precision oncology trials.
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- 2019
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5. Pembrolizumab plus Olaparib in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort A Study
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Evan Y. Yu, Josep M. Piulats, Gwenaelle Gravis, Peter C.C. Fong, Tilman Todenhöfer, Brigitte Laguerre, Jose A. Arranz, Stephane Oudard, Christophe Massard, Julia Heinzelbecker, Luke T. Nordquist, Joan Carles, Michael P. Kolinsky, Marinela Augustin, Howard Gurney, Ali Tafreshi, Xin Tong Li, Ping Qiu, Christian H. Poehlein, Charles Schloss, Johann S. de Bono, Institut Català de la Salut, [Yu EY] University of Washington and Fred Hutchinson Cancer Center, Seattle, WA, USA. [Piulats JM] Catalan Institute of Oncology, Barcelona, Spain. [Gravis G] Institut Paoli Calmettes, Marseille, France. [Fong PCC] Auckland City Hospital, Auckland, New Zealand. University of Auckland, Auckland, New Zealand. [Todenhöfer T] Studienpraxis Urologie, Nürtingen, Germany. [Laguerre B] Centre Eugène Marquis, Rennes, France. [Carles J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Male ,Anticossos monoclonals - Ús terapèutic ,Urology ,Medicaments antineoplàstics - Ús terapèutic ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS] ,Docetaxel ,Prostate-Specific Antigen ,Pròstata - Càncer - Tractament ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms::Prostatic Neoplasms, Castration-Resistant [DISEASES] ,Progression-Free Survival ,Prostatic Neoplasms, Castration-Resistant ,neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata::neoplasias prostáticas resistentes a la castración [ENFERMEDADES] ,Humans ,Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS] ,Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal [CHEMICALS AND DRUGS] ,Response Evaluation Criteria in Solid Tumors ,aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales [COMPUESTOS QUÍMICOS Y DROGAS] ,Aged - Abstract
Metastatic castration-resistant prostate cancer; Olaparib; Pembrolizumab Cáncer de próstata metastásico resistente a la castración; Olaparib; Pembrolizumab Càncer de pròstata metastàtic resistent a la castració; Olaparib; Pembrolizumab Background Pembrolizumab and olaparib have shown single-agent activity in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC). Objective To evaluate the efficacy and safety of pembrolizumab plus olaparib in mCRPC. Design, setting, and participants Cohort A of the phase 1b/2 KEYNOTE-365 study enrolled patients with molecularly unselected, docetaxel-pretreated mCRPC whose disease progressed within 6 mo of screening. Intervention Pembrolizumab 200 mg intravenously every 3 wk plus olaparib 400-mg capsule or 300-mg tablet orally twice daily. Outcome measurements and statistical analysis The primary endpoints were safety, confirmed prostate-specific antigen (PSA) response rate, and objective response rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, by blinded independent central review. The secondary endpoints included radiographic progression-free survival (rPFS) and overall survival (OS). Results and limitations Of 104 enrolled patients, 102 were treated. The median age was 70 yr (interquartile range [IQR], 65–76), and 59 patients (58%) had measurable disease as per RECIST v1.1. The median time from the first dose to database cutoff was 24 mo (IQR, 22–47). The confirmed PSA response rate was 15%. The confirmed ORR was 8.5% (five partial responses) for patients with measurable disease. The median rPFS was 4.5 mo (95% confidence interval [CI], 4.0–6.5) and median OS was 14 mo (95% CI, 10.4–18.2). Clinical activity was consistent across the programmed death ligand 1 (PD-L1)-positive and homologous recombination repair mutation subgroups. Treatment-related adverse events (TRAEs) occurred in 93 patients (91%). Grade 3–5 TRAEs occurred in 49 patients (48%). Six deaths (5.9%) were due to adverse events; two (myocardial infarction and unknown cause) were attributed to treatment. Limitations of the study include the single-arm design. Conclusions Pembrolizumab plus olaparib had a safety profile consistent with the profiles of the individual agents and demonstrated antitumor activity in previously treated patients with molecularly unselected, docetaxel-pretreated mCRPC.
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- 2023
6. Supplementary Figures S1-S10 from Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers
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Stefan Fröhling, Hanno Glimm, Wilko Weichert, Daniel Hübschmann, Evelin Schröck, Albrecht Stenzinger, Benedikt Brors, Barbara Klink, Christof von Kalle, Klaus Schulze-Osthoff, Michael Bitzer, Karsten Spiekermann, Philipp J. Jost, Nikolas von Bubnoff, Anna L. Illert, Melanie Boerries, Thomas Kindler, Christian H. Brandts, Jens Thomas Siveke, Sebastian Bauer, Gunnar Folprecht, Frederick Klauschen, Ulrich Keilholz, Richard F. Schlenk, Peter Schirmacher, Matthias Kroiss, Peter Hohenberger, Walter E. Aulitzky, Marinela Augustin, Ivo Buchhalter, Bettina Meißburger, Christina Geörg, Katrin Pfütze, Stephan Wolf, Ulrike Winter, Daniela Richter, Katja Beck, Roland Penzel, Olaf Neumann, Volker Endris, Andreas Laßmann, Leo Ruhnke, Michael Allgäuer, Daniel B. Lipka, Christoph E. Heilig, Veronica Teleanu, Dorothea Hanf, Lino Möhrmann, Laura Gieldon, Andreas Rump, Arne Jahn, Sebastian Uhrig, Martina Fröhlich, Jennifer Hüllein, Andreas Mock, Barbara Hutter, Simon Kreutzfeldt, Christoph Heining, and Peter Horak
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This file contains supplementary figures S1-S10.
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- 2023
7. Supplementary Tables S1-S7 from Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers
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Stefan Fröhling, Hanno Glimm, Wilko Weichert, Daniel Hübschmann, Evelin Schröck, Albrecht Stenzinger, Benedikt Brors, Barbara Klink, Christof von Kalle, Klaus Schulze-Osthoff, Michael Bitzer, Karsten Spiekermann, Philipp J. Jost, Nikolas von Bubnoff, Anna L. Illert, Melanie Boerries, Thomas Kindler, Christian H. Brandts, Jens Thomas Siveke, Sebastian Bauer, Gunnar Folprecht, Frederick Klauschen, Ulrich Keilholz, Richard F. Schlenk, Peter Schirmacher, Matthias Kroiss, Peter Hohenberger, Walter E. Aulitzky, Marinela Augustin, Ivo Buchhalter, Bettina Meißburger, Christina Geörg, Katrin Pfütze, Stephan Wolf, Ulrike Winter, Daniela Richter, Katja Beck, Roland Penzel, Olaf Neumann, Volker Endris, Andreas Laßmann, Leo Ruhnke, Michael Allgäuer, Daniel B. Lipka, Christoph E. Heilig, Veronica Teleanu, Dorothea Hanf, Lino Möhrmann, Laura Gieldon, Andreas Rump, Arne Jahn, Sebastian Uhrig, Martina Fröhlich, Jennifer Hüllein, Andreas Mock, Barbara Hutter, Simon Kreutzfeldt, Christoph Heining, and Peter Horak
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This excel file contains supplementary tables S1-S7.
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- 2023
8. Supplementary Methods from Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers
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Stefan Fröhling, Hanno Glimm, Wilko Weichert, Daniel Hübschmann, Evelin Schröck, Albrecht Stenzinger, Benedikt Brors, Barbara Klink, Christof von Kalle, Klaus Schulze-Osthoff, Michael Bitzer, Karsten Spiekermann, Philipp J. Jost, Nikolas von Bubnoff, Anna L. Illert, Melanie Boerries, Thomas Kindler, Christian H. Brandts, Jens Thomas Siveke, Sebastian Bauer, Gunnar Folprecht, Frederick Klauschen, Ulrich Keilholz, Richard F. Schlenk, Peter Schirmacher, Matthias Kroiss, Peter Hohenberger, Walter E. Aulitzky, Marinela Augustin, Ivo Buchhalter, Bettina Meißburger, Christina Geörg, Katrin Pfütze, Stephan Wolf, Ulrike Winter, Daniela Richter, Katja Beck, Roland Penzel, Olaf Neumann, Volker Endris, Andreas Laßmann, Leo Ruhnke, Michael Allgäuer, Daniel B. Lipka, Christoph E. Heilig, Veronica Teleanu, Dorothea Hanf, Lino Möhrmann, Laura Gieldon, Andreas Rump, Arne Jahn, Sebastian Uhrig, Martina Fröhlich, Jennifer Hüllein, Andreas Mock, Barbara Hutter, Simon Kreutzfeldt, Christoph Heining, and Peter Horak
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This file contains supplementary methods and references.
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- 2023
9. Data from Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers
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Stefan Fröhling, Hanno Glimm, Wilko Weichert, Daniel Hübschmann, Evelin Schröck, Albrecht Stenzinger, Benedikt Brors, Barbara Klink, Christof von Kalle, Klaus Schulze-Osthoff, Michael Bitzer, Karsten Spiekermann, Philipp J. Jost, Nikolas von Bubnoff, Anna L. Illert, Melanie Boerries, Thomas Kindler, Christian H. Brandts, Jens Thomas Siveke, Sebastian Bauer, Gunnar Folprecht, Frederick Klauschen, Ulrich Keilholz, Richard F. Schlenk, Peter Schirmacher, Matthias Kroiss, Peter Hohenberger, Walter E. Aulitzky, Marinela Augustin, Ivo Buchhalter, Bettina Meißburger, Christina Geörg, Katrin Pfütze, Stephan Wolf, Ulrike Winter, Daniela Richter, Katja Beck, Roland Penzel, Olaf Neumann, Volker Endris, Andreas Laßmann, Leo Ruhnke, Michael Allgäuer, Daniel B. Lipka, Christoph E. Heilig, Veronica Teleanu, Dorothea Hanf, Lino Möhrmann, Laura Gieldon, Andreas Rump, Arne Jahn, Sebastian Uhrig, Martina Fröhlich, Jennifer Hüllein, Andreas Mock, Barbara Hutter, Simon Kreutzfeldt, Christoph Heining, and Peter Horak
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The clinical relevance of comprehensive molecular analysis in rare cancers is not established. We analyzed the molecular profiles and clinical outcomes of 1,310 patients (rare cancers, 75.5%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults with incurable cancers. On the basis of 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment, in 88% of cases. Recommended therapies were administered in 362 of 1,138 patients (31.8%) and resulted in significantly improved overall response and disease control rates (23.9% and 55.3%) compared with previous therapies, translating into a progression-free survival ratio >1.3 in 35.7% of patients. These data demonstrate the benefit of molecular stratification in rare cancers and represent a resource that may promote clinical trial access and drug approvals in this underserved patient population.Significance:Rare cancers are difficult to treat; in particular, molecular pathogenesis–oriented medical therapies are often lacking. This study shows that whole-genome/exome and RNA sequencing enables molecularly informed treatments that lead to clinical benefit in a substantial proportion of patients with advanced rare cancers and paves the way for future clinical trials.See related commentary by Eggermont et al., p. 2677.This article is highlighted in the In This Issue feature, p. 2659
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- 2023
10. CD19 expression is maintained in DLBCL patients after treatment with tafasitamab plus lenalidomide in the L-MIND study
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Marinela Augustin, Johannes Duell, Sabine Geiger, Jan Endell, Aleš Obr, Sumeet Ambarkhane, Andreas Rosenwald, Ian M. Silverman, and Hao Liu
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Oncology ,Cancer Research ,medicine.medical_specialty ,biology ,business.industry ,Hematology ,Antibodies, Monoclonal, Humanized ,CD19 ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,biology.protein ,Humans ,Lymphoma, Large B-Cell, Diffuse ,business ,Lenalidomide ,After treatment ,medicine.drug - Abstract
CD19 is an important target for novel anti-lymphoma treatments as it is broadly and homogenously expressed across many B-cell malignancies [1,2]. Approximately 30–50% of patients with diffuse large...
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- 2021
11. Everolimus after failure of one prior VEGF-targeted therapy in metastatic renal cell carcinoma : Final results of the MARC-2 trial
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Iris Benz-Rüd, Frederik Roos, Marc-Oliver Grimm, Peter J. Goebell, Michael Stöckle, Norbert Marschner, Viktor Grünwald, Marinela Augustin, Michael Staehler, Dunja Klein, Daniel C. Christoph, Fabian Brüning, Karin Potthoff, Johanna Harde, and Arnulf Stenzl
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Male ,Cancer Research ,Medizin ,Kaplan-Meier Estimate ,Gastroenterology ,Body Mass Index ,0302 clinical medicine ,6-month PFS rate ,Renal cell carcinoma ,Clinical endpoint ,Prospective Studies ,Fatigue ,Aged, 80 and over ,Hazard ratio ,Anemia ,Middle Aged ,Kidney Neoplasms ,Progression-Free Survival ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Female ,Gastrointestinal Hemorrhage ,phase IV ,medicine.drug ,Adult ,second-line ,medicine.medical_specialty ,renal cell carcinoma ,Antineoplastic Agents ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,ddc:610 ,Adverse effect ,Survival rate ,Carcinoma, Renal Cell ,Aged ,Proportional Hazards Models ,Stomatitis ,Everolimus ,Proportional hazards model ,business.industry ,medicine.disease ,everolimus ,Receptors, Vascular Endothelial Growth Factor ,business - Abstract
MARC‐2, a prospective, multicenter phase IV trial, aimed to investigate clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with everolimus after failure of one initial vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR‐TKI) therapy and to identify subgroups benefiting most, based on clinical characteristics and biomarkers. Patients with clear cell mRCC failing one initial VEGFR‐TKI received everolimus until progression or unacceptable toxicity. Primary endpoint was 6‐month progression‐free survival rate (6moPFS). Secondary endpoints were overall response rate (ORR), PFS, overall survival (OS), and safety. Between 2011 and 2015, 63 patients were enrolled. Median age was 65.4 years (range 43.3‐81.1). 6moPFS was 39.3% (95% confidence interval [CI], 27.0‐51.3) overall, 54.4% (95% CI, 35.2‐70.1) vs 23.7% (95% CI, 10.5‐39.9) for patients aged ≥65 vs 25 vs ≤25 kg/m2. A Cox proportional hazards model confirmed a longer PFS for patients aged ≥65 years (hazard ratio [HR] 0.46; 95% CI, 0.26‐0.80) and a longer OS for patients with BMI >25 kg/m2 (HR 0.36; 95% CI, 0.18‐0.71). Median PFS and median OS were 3.8 months (95% CI, 3.2‐6.2) and 16.8 months (95% CI, 14.3‐24.3). ORR was 7.9% and disease control rate was 60.3%. No new safety signals emerged. Most common adverse events were stomatitis (31.7%), fatigue (31.7%), and anemia (30.2%). One patient died from treatment‐related upper gastrointestinal hemorrhage. Everolimus remains a safe and effective treatment option for mRCC patients after one prior VEGFR‐TKI therapy. Patients aged ≥65 years and patients with BMI >25 kg/m2 benefited most.
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- 2022
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12. Preinfection laboratory parameters may predict COVID‐19 severity in tumor patients
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Markus Kapp, Peter Reimer, Thomas Kubin, Ralph Naumann, Clemens Müller-Naendrup, Ernst Späth‐Schwalbe, Frank Kullmann, Romina Roesch, Helmut Lambertz, Martin Bentz, Alexander Kiani, Markus Schaich, Holger Hebart, Frank Hartmann, Ulrich Kaiser, Ruth Seggewiss-Bernhardt, Jens‐Marcus Chemnitz, Gerald Illerhaus, Clemens M. Wendtner, Thomas Südhoff, Jörg Baesecke, Ullrich Graeven, and Marinela Augustin
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Adult ,Male ,0301 basic medicine ,tumor ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Disease ,Severity of Illness Index ,Asymptomatic ,SARS‐CoV‐2 ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,neutrophils ,COVID‐19 ,Neoplasms ,Internal medicine ,Severity of illness ,Humans ,cancer ,Medicine ,Radiology, Nuclear Medicine and imaging ,Young adult ,Child ,RC254-282 ,Aged ,Retrospective Studies ,Original Research ,Aged, 80 and over ,SARS-CoV-2 ,business.industry ,COVID-19 ,Clinical Cancer Research ,biomarkers ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cancer ,Retrospective cohort study ,Middle Aged ,medicine.disease ,030104 developmental biology ,Oncology ,Child, Preschool ,030220 oncology & carcinogenesis ,Cohort ,Absolute neutrophil count ,Female ,medicine.symptom ,business - Abstract
Background Infection with SARS‐CoV‐2 leads to COVID‐19, the course of which is highly variable and depends on numerous patient‐specific risk factors. Patients with tumor diseases are considered to be more susceptible to severe COVID‐19; however, they also represent a heterogeneous group of individuals with variable risk. Identifying specific risk factors for a severe course of COVID‐19 in patients with cancer is of great importance. Methods Patients diagnosed with solid tumors or hematological malignancies and PCR‐confirmed SARS‐CoV‐2 infection were included into the multicentric ADHOK (Arbeitsgemeinschaft der Hämatologen und Onkologen im Krankenhaus e.V.) coronavirus tumor registry. Detailed information about the patients’ cancer disease, treatment, and laboratory parameters prior to infection, was collected retrospectively. The outcome of the SARS‐CoV‐2 infection was graded according to the WHO. Results A total of 195 patients (68% with solid neoplasms and 32% with hematological malignancies) were included in the registry. Overall, the course of the SARS‐CoV‐2 infection varied greatly, as 69% of all patients were either asymptomatic or encountered a mild to moderate course, while 23% of the cohort died from COVID‐19. In multivariable analysis, preinfection laboratory parameters (determined at least 10 days and a median of 21 days before the first documentation of SARS‐CoV‐2 infection) significantly correlated with severe course of the disease. Out of these, the absolute neutrophil count prior to infection showed the strongest association with COVID‐19‐related death. Conclusion The course of COVID‐19 in patients with tumor diseases is highly variable. Preinfection laboratory parameters may aid to identify patients at risk for severe COVID‐19 at an early stage prior to infection with the virus. German Clinical Trials Register identification: DRKS00023012., The course of SARS‐CoV‐2 infection in tumor patients is highly variable. Subgroups at risk for severe COVID‐19 are yet imprecisely defined. Laboratory parameters prior to infection, particularly pre‐infection neutrophils, may identify patients at risk for death.
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- 2021
13. Abstract CT022: Five-year efficacy and safety of tafasitamab in patients with relapsed or refractory DLBCL: Final results from the phase II L-MIND study
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Johannes Duell, Pau Abrisqueta, Marc Andre, Marinela Augustin, Gianluca Gaidano, Eva González Barca, Wojciech Jurczak, Nagesh Kalakonda, Anna Marina Liberati, Kami J. Maddocks, Tobias Menne, Zsolt Nagy, Olivier Tournilhac, Abhishek Bakuli, Aasim Amin, Konstantin Gurbanov, and Gilles Salles
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Cancer Research ,Oncology - Abstract
Background: Tafasitamab, an anti-CD19 immunotherapy that enhances antibody-dependent cellular cytotoxicity and phagocytosis, received accelerated approval in the USA and conditional authorization in Europe in combination with lenalidomide (LEN) for patients (pts) with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem cell transplant (ASCT) based on the results of the open-label, multicenter, single-arm, Phase II L-MIND study (NCT02399085; Salles G, et al. Lancet Oncol 2020, Duell J, et al. Haematologica 2021). Here, we report the final, 5-year follow-up of L-MIND. Data cut-off was Nov 14, 2022. Methods: Pts were aged ≥18 years with ASCT-ineligible R/R DLBCL, 1-3 prior systemic therapies (including a CD20-targeting regimen), and ECOG PS 0-2. Tafasitamab (12 mg/kg) was given for up to 12 cycles in combination with LEN (25 mg), then as monotherapy until disease progression (PD) or unacceptable toxicity. The primary endpoint was best objective response rate (ORR; complete response [CR] or partial response [PR], by independent radiology committee). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and incidence and severity of adverse events (AEs). Exploratory analyses evaluated efficacy endpoints by prior lines of therapy (pLoT). Results: Of 81 pts enrolled, 80 were treated (full analysis set [FAS]). The ORR (FAS) of 57.5% [95% CI: 45.9-68.5], with CR of 41.2% [30.4-51.6] (n=33) and PR of 16.2% [8.9-26.2] (n=13), was generally consistent with the primary and 3-year analyses. Median DoR was not reached (NR) with median follow up (mFU) of 44.0 months [29.9-57.0]. Median PFS was 11.6 months [5.7-45.7] (mFU 45.6 [22.9-57.6]) and median OS was 33.5 months [18.3-NR] (mFU 65.6 [59.9-70.3]). At data cut-off, OS was >60 months in 21 pts (18 with best response of CR, 1 PR, 1 stable disease and 1 PD), including 14 with 1 pLoT and 7 with ≥2 pLoT. Pts with 1 pLoT (n=40) in the FAS had higher ORR (67.5%; 52.5% CR [n=21] and 15% PR [n=6]) compared to pts with ≥2 pLoT (n=40; 47.5%; 30% CR [n=12] and 17.5% PR [n=7]). However, median DoR was not reached for both subgroups, indicating similar long-term efficacy for responders. AEs were consistent with previous reports and manageable; incidence declined after transition from combination to tafasitamab monotherapy and again with monotherapy >2 years. Conclusion: The final, 5-year analysis of L-MIND showed prolonged durable responses with tafasitamab + LEN combination therapy, followed by long-term tafasitamab monotherapy, in pts with R/R DLBCL ineligible for ASCT, with median DoR not reached after 44 months mFU. No new safety signals were identified, confirming the tolerability profile observed with earlier data cuts. These long-term data suggest that this immunotherapy may have curative potential that is being explored in further studies. Citation Format: Johannes Duell, Pau Abrisqueta, Marc Andre, Marinela Augustin, Gianluca Gaidano, Eva González Barca, Wojciech Jurczak, Nagesh Kalakonda, Anna Marina Liberati, Kami J. Maddocks, Tobias Menne, Zsolt Nagy, Olivier Tournilhac, Abhishek Bakuli, Aasim Amin, Konstantin Gurbanov, Gilles Salles. Five-year efficacy and safety of tafasitamab in patients with relapsed or refractory DLBCL: Final results from the phase II L-MIND study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT022.
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- 2023
14. Corrigendum to 'Pembrolizumab plus Olaparib in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort A Study' [Eur Urol 83 (2023) 15–26]
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Evan Y. Yu, Josep M. Piulats, Gwenaelle Gravis, Peter C.C. Fong, Tilman Todenhöfer, Brigitte Laguerre, Jose A. Arranz, Stephane Oudard, Christophe Massard, Julia Heinzelbecker, Luke T. Nordquist, Joan Carles, Michael P. Kolinsky, Marinela Augustin, Howard Gurney, Ali Tafreshi, Xin Tong Li, Ping Qiu, Christian H. Poehlein, Charles Schloss, and Johann S. de Bono
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Urology - Published
- 2023
15. MP24-14 PEMBROLIZUMAB (PEMBRO) PLUS OLAPARIB IN PATIENTS WITH DOCETAXEL-PRETREATED METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC): UPDATED RESULTS FROM KEYNOTE-365 COHORT A WITH A MINIMUM OF 11 MONTHS OF FOLLOW-UP FOR ALL PATIENTS
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Evan Y. Yu, Johann S. de Bono, Charles Schloss, Ali Tafreshi, Gwenaelle Gravis, Michael Stoeckle, Howard Gurney, Josep M. Piulats, Marinela Augustin, Joan Carles, Xin Tong Li, Christian Heinrich Poehlein, Luke T. Nordquist, Brigitte Laguerre, Tilman Todenhoefer, Christophe Massard, Peter C.C. Fong, Jose Angel Arranz Arija, Michael Kolinsky, and Stéphane Oudard
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Antitumor activity ,Oncology ,medicine.medical_specialty ,business.industry ,Urology ,Pembrolizumab ,Castration resistant ,medicine.disease ,Olaparib ,chemistry.chemical_compound ,Prostate cancer ,Docetaxel ,chemistry ,Internal medicine ,Cohort ,medicine ,In patient ,business ,medicine.drug - Abstract
INTRODUCTION AND OBJECTIVE:The phase 1/2 KEYNOTE-365 study (NCT02861573) previously showed that pembro+olaparib was associated with antitumor activity and acceptable safety in molecularly unselecte...
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- 2021
16. Trabectedin for Patients with Advanced Soft Tissue Sarcoma: A Non-Interventional, Prospective, Multicenter, Phase IV Trial
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Viktor Grünwald, Daniel Pink, Gerlinde Egerer, Enrico Schalk, Marinela Augustin, Christoph K. W. Deinzer, Viola Kob, Dietmar Reichert, Maxim Kebenko, Stephan Brandl, Dennis Hahn, Lars H. Lindner, Mathias Hoiczyk, Uta Ringsdorf, Lars C. Hanker, Dirk Hempel, Beatriz De Rivas, Tobias Wismann, and Philipp Ivanyi
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trabectedin ,STS ,sarcoma ,non-interventional ,prospective ,Cancer Research ,Oncology ,Medizin - Abstract
This non-interventional, prospective phase IV trial evaluated trabectedin in patients with soft tissue sarcoma (STS) in real-life clinical practice across Germany. The primary endpoints were progression-free survival (PFS) rates at 3 and 6 months, as defined by investigators. Overall, 128 patients from 19 German sites were evaluated for efficacy and 130 for safety. Median age was 58.5 years (range: 23–84) and leiomyosarcoma was the most frequent histotype (n = 45; 35.2%). Trabectedin was mostly used as second/third-line treatment (n = 91; 71.1%). Median PFS was 5.2 months (95% CI: 3.3–6.7), with 60.7% and 44.5% of patients free from progression at 3 and 6 months, respectively. Median overall survival was 15.2 months (95% CI: 9.6–21.4). One patient achieved a complete and 14 patients a partial response, conferring an objective response rate of 11.7%. Decreases in white blood cells (27.0% of patients), platelets (16.2%) and neutrophils (13.1%) and increased alanine aminotransferase (10.8%) were the most common trabectedin-related grade 3/4 adverse drug reactions. Two deaths due to pneumonia and sepsis were considered trabectedin-related. Trabectedin confers clinically meaningful activity in patients with multiple STS histotypes, comparable to that previously observed in clinical trials and other non-interventional studies, and with a manageable safety profile.
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- 2022
17. Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma
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Pau Abrisqueta, Martin Dreyling, Johannes Duell, Marc André, Eva González-Barca, Aleš Obr, Gilles Salles, Nagesh Kalakonda, Tobias Menne, Olivier Tournilhac, Gianluca Gaidano, Anna Marina Liberati, Sven de Vos, Sumeet Ambarkhane, Wojciech Jurczak, Johannes Weirather, Maren Dirnberger-Hertweck, Kami J. Maddocks, Zsolt Nagy, Andreas Rosenwald, Marinela Augustin, UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), Institut Català de la Salut, [Duell J] Medizinische Klinik und Poliklinik II, Universitätsklinik Würzburg, Würzburg, Germany. [Maddocks KJ] Department of Internal Medicine, Arthur G James Comprehensive Cancer Center, Ohio State University Wexner Medical Center, Columbus, OH, USA. [González-Barca E] Department of Hematology, Institut Catalá d’Oncologia (ICO), Hospital Duran i Reynals, Universitat de Barcelona, Barcelona, Spain. [Jurczak W] Maria Sklodowska–Curie National Research Institute of Oncology, Kraków, Poland. [Liberati AM] Università degli Studi di Perugia, Azienda Ospedaliera Santa Maria di Terni, Terni, Italy. [De Vos S] Department of Medicine, Ronald Reagan UCLA Medical Center, Santa Monica, CA, USA. [Abrisqueta P] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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medicine.medical_specialty ,Cèl·lules B ,Cèl·lules B - Tumors - Tractament ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Antibodies, Monoclonal, Humanized ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Transplantation, Autologous ,Gastroenterology ,Article ,Quimioteràpia combinada ,03 medical and health sciences ,0302 clinical medicine ,Autologous stem-cell transplantation ,Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, Large B-Cell, Diffuse [DISEASES] ,Refractory ,Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Clinical endpoint ,Lymphatic diseases ,Humans ,Refractory Diffuse Large B-Cell Lymphoma ,Lenalidomide ,B cells ,Transplantation of organs ,business.industry ,Malalties del sistema limfàtic ,Hematopoietic Stem Cell Transplantation ,terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Hematology ,3. Good health ,Transplantation ,Trasplantament d'òrgans ,Regimen ,Treatment Outcome ,Tolerability ,neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B::linfoma de células B grandes difuso [ENFERMEDADES] ,030220 oncology & carcinogenesis ,Avaluació de resultats (Assistència sanitària) ,Lymphoma, Large B-Cell, Diffuse ,business ,030215 immunology ,medicine.drug - Abstract
Tafasitamab; B-cell lymphoma Tafasitamab; Linfoma de células B Tafasitamab; Limfoma de cèl·lules B Tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, combined with the immunomodulatory drug lenalidomide was clinically active with a good tolerability profile in the open-label, single-arm, phase II L-MIND study of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem-cell transplantation. To assess long-term outcomes, we report an updated analysis with ≥35 months’ follow-up. Patients were aged >18 years, had received one to three prior systemic therapies (including ≥1 CD20-targeting regimen) and Eastern Cooperative Oncology Group performance status 0-2. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during cycles 1-3, then every 2 weeks during cycles 4-12. Lenalidomide (25 mg orally) was administered on days 1-21 of cycles 1-12. After cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression. The primary endpoint was best objective response rate. After ≥35 months’ follow-up (data cut-off: October 30, 2020), the objective response rate was 57.5% (n=46/80), including a complete response in 40.0% of patients (n=32/80) and a partial response in 17.5% of patients (n=14/80). The median duration of response was 43.9 months (95% confidence interval [95% CI]: 26.1-not reached), the median overall survival was 33.5 months (95% CI: 18.3-not reached) and the median progression-free survival was 11.6 months (95% CI: 6.3-45.7). There were no unexpected toxicities. Subgroup analyses revealed consistent long-term efficacy results across most subgroups of patients. This extended follow-up of L-MIND confirms the long duration of response, meaningful overall survival, and well-defined safety profile of tafasitamab plus lenalidomide followed by tafasitamab monotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma ineligible for autologous stem cell transplantation. ClinicalTrials.gov identifier: NCT02399085.
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- 2021
18. Thrombospondin-2 and LDH Are Putative Predictive Biomarkers for Treatment with Everolimus in Second-Line Metastatic Clear Cell Renal Cell Carcinoma (MARC-2 Study)
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Viktor Grünwald, Barbara Seliger, Iris Benz-Rüd, Arnulf Stenzl, Frederik C. Roos, Sebastian Hölters, Peter J. Goebell, Johanna Harde, Marinela Augustin, Philip Zeuschner, Anja Mueller, Kerstin Junker, Michael Staehler, Daniel C. Christoph, Fabian Brüning, Hagen S. Bachmann, Michael Stöckle, and Marc-Oliver Grimm
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0301 basic medicine ,Oncology ,second-line ,Cancer Research ,medicine.medical_specialty ,Medizin ,urologic and male genital diseases ,metastatic renal cell carcinoma ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Renal cell carcinoma ,Polymorphism (computer science) ,Lactate dehydrogenase ,Internal medicine ,medicine ,ddc:610 ,RC254-282 ,Predictive biomarker ,Everolimus ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,everolimus ,Clear cell renal cell carcinoma ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,biomarker ,phase IV ,Biomarker (medicine) ,business ,Clear cell ,medicine.drug - Abstract
Simple Summary: Treatment of metastatic renal cell carcinoma (mRCC) remains a challenge due to the lack of biomarkers indicating the optimal drug for each patient. This study analyzed blood samples of patients with predominant clear cell mRCC who were treated with the mTOR inhibitor everolimus after failure of one prior tumor therapy. In an exploratory approach, predictive blood biomarkers were searched. We found lower levels of the protein thrombospondin-2 (TSP-2) at the start of the therapy and higher lactate dehydrogenase (LDH) levels in serum two weeks after therapy initiation to be associated with therapy response. Of note, these blood biomarkers had a higher predictive value than baseline patient parameters or risk classifications. Polymorphisms in the mTOR gene appeared to be associated with therapy response, but were not significant. To conclude, it seems feasible to identify patients showing longtime responses to everolimus and possible to increase tumor therapy response rates based on biomarkers for individual therapy selection. Abstract: There is an unmet need for predictive biomarkers in metastatic renal cell carcinoma (mRCC) therapy. The phase IV MARC-2 trial searched for predictive blood biomarkers in patients with predominant clear cell mRCC who benefit from second-line treatment with everolimus. In an exploratory approach, potential biomarkers were assessed employing proteomics, ELISA, and polymorphism analyses. Lower levels of angiogenesis-related protein thrombospondin-2 (TSP-2) at baseline (≤665 parts per billion, ppb) identified therapy responders with longer median progression-free survival (PFS; ≤665 ppb at baseline: 6.9 months vs. 1.8, p = 0.005). Responders had higher lactate dehydrogenase (LDH) levels in serum two weeks after therapy initiation (>27.14 nmol/L), associated with a longer median PFS (3.8 months vs. 2.2, p = 0.013) and improved overall survival (OS; 31.0 months vs. 14.0 months, p < 0.001). Baseline TSP-2 levels had a stronger relation to PFS (HR 0.36, p = 0.008) than baseline patient parameters, including IMDC score. Increased serum LDH levels two weeks after therapy initiation were the best predictor for OS (HR 0.21, p < 0.001). mTOR polymorphisms appeared to be associated with therapy response but were not significant. Hence, we identified TSP-2 and LDH as promising predictive biomarkers for therapy response on everolimus after failure of one VEGF-targeted therapy in patients with clear cell mRCC.
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- 2021
19. 612P Pembrolizumab (pembro) plus olaparib in patients with docetaxel-pretreated metastatic castration-resistant prostate cancer (mCRPC): Update of KEYNOTE-365 cohort A with a minimum of 11 months of follow-up for all patients
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Xin Tong Li, Evan Y. Yu, Christophe Massard, G. Gravis, Peter C.C. Fong, Charles Schloss, Howard Gurney, Joan Carles, Josep M. Piulats, Tilman Todenhöfer, Luke T. Nordquist, B. Laguerre, Michael Paul Kolinsky, Ali Tafreshi, Michael Stoeckle, J.A. Arranz Arija, Christian Heinrich Poehlein, Marinela Augustin, J.S. de Bono, and Stéphane Oudard
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Oncology ,medicine.medical_specialty ,business.industry ,Hematology ,Pembrolizumab ,Castration resistant ,medicine.disease ,Olaparib ,Prostate cancer ,chemistry.chemical_compound ,Docetaxel ,chemistry ,Internal medicine ,Cohort ,medicine ,In patient ,business ,medicine.drug - Published
- 2021
20. Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers
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Stefan Fröhling, Albrecht Stenzinger, Ivo Buchhalter, Peter Hohenberger, Sebastian Bauer, Ulrich Keilholz, Andreas Mock, Daniel B. Lipka, Benedikt Brors, Michael Allgäuer, Andreas Rump, Stephan Wolf, Melanie Boerries, Klaus Schulze-Osthoff, Gunnar Folprecht, Katrin Pfütze, Christof von Kalle, Christian Brandts, Michael Bitzer, Laura Gieldon, Arne Jahn, Peter Schirmacher, Olaf Neumann, Matthias Kroiss, Barbara Klink, Daniela Richter, Sebastian Uhrig, Peter Horak, Ulrike Winter, Nikolas von Bubnoff, Barbara Hutter, Walter E. Aulitzky, Wilko Weichert, Jennifer Hüllein, Philipp J. Jost, Veronica Teleanu, Thomas Kindler, Leo Ruhnke, Martina Fröhlich, Christoph E. Heilig, Katja Beck, Karsten Spiekermann, Volker Endris, Evelin Schröck, Frederick Klauschen, Dorothea Hanf, Simon Kreutzfeldt, Daniel Hübschmann, Jens T. Siveke, Bettina Meißburger, Lino Möhrmann, Richard F. Schlenk, Andreas Laßmann, Anna Lena Illert, Roland Penzel, Christina Geörg, Christoph Heining, Marinela Augustin, and Hanno Glimm
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Oncology ,medicine.medical_specialty ,business.industry ,Genetic counseling ,MEDLINE ,Medizin ,Cancer ,medicine.disease ,Clinical trial ,Transcriptome ,Internal medicine ,Medicine ,Clinical significance ,Observational study ,business ,Exome - Abstract
The clinical relevance of comprehensive molecular analysis in rare cancers is not established. We analyzed the molecular profiles and clinical outcomes of 1,310 patients (rare cancers, 75.5%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults with incurable cancers. On the basis of 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment, in 88% of cases. Recommended therapies were administered in 362 of 1,138 patients (31.8%) and resulted in significantly improved overall response and disease control rates (23.9% and 55.3%) compared with previous therapies, translating into a progression-free survival ratio >1.3 in 35.7% of patients. These data demonstrate the benefit of molecular stratification in rare cancers and represent a resource that may promote clinical trial access and drug approvals in this underserved patient population. Significance: Rare cancers are difficult to treat; in particular, molecular pathogenesis–oriented medical therapies are often lacking. This study shows that whole-genome/exome and RNA sequencing enables molecularly informed treatments that lead to clinical benefit in a substantial proportion of patients with advanced rare cancers and paves the way for future clinical trials. See related commentary by Eggermont et al., p. 2677. This article is highlighted in the In This Issue feature, p. 2659
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- 2021
21. Efficacy of Tafasitamab (MOR208) Combined with Lenalidomide in Patients with High-Risk Relapsed or Refractory Diffuse Large B-Cell Lymphoma in the L-Mind Study
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Federica Cavallo, Johannes Weirather, Johannes Duell, Nagesh Kalakonda, Gilles Salles, Zsolt Nagy, Juan-Manuel Sancho, Marinela Augustin, Sumeet Ambarkhane, Eva González-Barca, Kami J. Maddocks, Pau Abrisqueta, and Carlos Panizo
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medicine.medical_specialty ,education.field_of_study ,business.industry ,Immunology ,Population ,Cell Biology ,Hematology ,Biochemistry ,Regimen ,International Prognostic Index ,Internal medicine ,medicine ,Refractory Diffuse Large B-Cell Lymphoma ,Tumor biopsy ,In patient ,Response Duration ,business ,education ,Lenalidomide ,medicine.drug - Abstract
Introduction Patients with diffuse large B-cell lymphoma (DLBCL) that is refractory to primary immunochemotherapy are well recognized as a high-risk population with poor prognosis, and have a typical median overall survival (OS) of 6-13 months [Farooq U, et al. 2017]. Patients with 'double-hit' (MYCand eitherBCL2orBCL6) and 'triple-hit' (MYC, BCL2andBCL6) genetic aberrations are also considered to be a high-risk/poor prognosis group [Davies A. 2019]. Tafasitamab (MOR208) is an Fc-enhanced, humanized, monoclonal anti-CD19 antibody that is under investigation in combination with lenalidomide (LEN) in autologous stem cell transplant (ASCT)-ineligible patients with relapsed/refractory (R/R) DLBCL in the Phase II L-MIND study (NCT02399085) [Salles G, et al. 2020]. We report efficacy data for patients with high-risk DLBCL (primary refractory disease and double/triple-hit lymphoma [DHL/THL]) who received tafasitamab + LEN in L-MIND (data cut-off: Nov 30, 2019; median follow-up for OS, 31.8 months). Methods In the L-MIND study, patients enrolled were aged ≥18 years with R/R DLBCL (1-3 prior systemic therapies, including ≥1 CD20-targeting regimen), with an Eastern Cooperative Oncology Group performance status of 0-2 and ineligible for ASCT. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during Cycles 1-3 with a loading dose on Cycle 1 Day 4, then every 2 weeks during Cycles 4-12. LEN (25 mg orally) was administered on Days 1-21 of Cycles 1-12. After Cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression. The primary endpoint was objective response rate (ORR) (partial response [PR] + complete response [CR]), assessed centrally by an independent review committee. Primary refractory disease was defined as no response (CR or PR) to or progression during or within 6 months of frontline DLBCL therapy.MYC,BCL2andBCL6aberrations were determined via fluorescencein situhybridization using tumor biopsy. Results The L-MIND cohort included 15 patients with primary refractory DLBCL and two patients with DHL/THL. Patients with primary refractory DLBCL at baseline had a median age of 73 years (range 48-82; n=9 ≥70 years) and were previously exposed to a median of 2 lines of treatment (range 1-4). Of these patients, ten had stage III/IV disease, ten showed lactate dehydrogenase greater than the upper normal limit, 12 patients had germinal center B-cell DLBCL and eight exhibited intermediate-high or high-risk International Prognostic Index (IPI) status at study baseline. All 15 patients received R-CHOP or equivalent as first-line therapy; two patients previously achieved no response, whereas 13 patients had relapsed within 6 months (ten had achieved a CR and 3 a PR) after frontline therapy. Six patients had received only 1 prior therapy, whereas nine patients had ≥2 lines before L-MIND enrollment. Median time to progression after first-line therapy was 162 days (range 28-182 days); two of 15 patients had progressed within 90 days. Of the 15 patients, 13 were refractory to their last line of therapy before L-MIND. In the 15 patients with primary refractory disease, ORR was 53.3% (95% confidence interval [CI]: 26.6-78.7) and the CR rate was 33.3%, with a 30-month duration of response (DOR) rate of 50% (95% CI: 15.2-77.5) - median DOR not reached (NR). Individual response duration is shown in Figure 1 (swimmer plot): four patients who achieved CR remain in remission after >30 months. Median progression-free survival (PFS) was 5.3 months (95% CI: 0.9-NR) and PFS rate at 30 months was 33.9% (95% CI: 11.0-58.8). Median OS was 13.8 months (95% CI: 1.3-NR) and OS at 36 months was 38.1% (95% CI: 14.6-61.6). Regarding patients with DHL/THL: one with DHL achieved PR only; another patient with THL (also part of the primary refractory subgroup) achieved CR and remains in remission after >30 months. Conclusions The combination of tafasitamab + LEN showed encouraging activity, with a clinically meaningful ORR and CR rate in patients with primary refractory DLBCL, and positive responses in DHL and THL. Patients with primary refractory disease were frequently ≥70 years with stage III/IV disease and poor-risk IPI scores. Although these data should be interpreted with caution due to the small patient subgroup sizes, these clinically relevant results warrant further research with this immunotherapy in patients with difficult-to-treat DLBCL. Disclosures González-Barca: MorphoSys:Other;Janssen:Consultancy, Honoraria;Sandoz:Consultancy;Gilead:Consultancy;Roche:Honoraria;Takeda:Honoraria;Abbvie:Honoraria;Celgene:Consultancy;Kiowa:Consultancy;Celtrion:Consultancy.Duell:Morphosys:Research Funding.Sancho:Bristol-Myers Squibb:Honoraria;Celgene:Consultancy, Honoraria;Gilead:Consultancy, Honoraria;Janssen:Consultancy, Honoraria;Kern-Pharma:Consultancy, Honoraria;Novartis:Consultancy, Honoraria;Roche:Consultancy, Honoraria;Takeda:Honoraria;Celltrion:Consultancy;Sandoz:Consultancy.Nagy:MorphoSys AG:Patents & Royalties.Abrisqueta:Celgene:Consultancy, Honoraria;AbbVie:Consultancy, Honoraria, Speakers Bureau;Roche:Consultancy, Honoraria, Speakers Bureau;Janssen:Consultancy, Honoraria, Speakers Bureau.Panizo:Clínica Universidad de Navarra:Current Employment;Bristol-Myers Squibb, Kyowa Kirin:Speakers Bureau;Janssen, Roche:Membership on an entity's Board of Directors or advisory committees.Augustin:Morphosys:Research Funding;AstraZeneca:Consultancy, Research Funding;Roche:Consultancy;Novartis:Consultancy, Research Funding;Merck:Consultancy;IPSEN:Consultancy, Research Funding;Pfizer:Consultancy, Research Funding;BMS:Consultancy, Research Funding.Weirather:MorphoSys AG:Current Employment.Ambarkhane:MorphoSys AG:Current Employment.Maddocks:Seattle Genetics:Consultancy, Honoraria;Celgene:Consultancy, Honoraria;Pharmacyclics:Consultancy, Honoraria;Morphosys:Consultancy, Honoraria;ADC Therapeutics, AstraZeneca:Consultancy;BMS:Consultancy, Research Funding;Karyopharm:Consultancy.Kalakonda:Celgene:Research Funding.Salles:BMS/Celgene:Honoraria, Other: consultancy or advisory role;Takeda:Honoraria;Karyopharm:Honoraria;Genmab:Honoraria, Other;Debiopharm:Consultancy, Honoraria, Other: consultancy or advisory role;Autolos:Other: consultancy or advisory role;Abbvie:Other: consultancy or advisory role;Roche:Honoraria, Other: consultancy or advisory role;Novartis:Honoraria, Other: consultancy or advisory role;MorphoSys:Honoraria, Other: consultancy or advisory role;Janssen:Honoraria, Other: consultancy or advisory role;Epizyme:Honoraria, Other: consultancy or advisory role;Kite, a Gilead Company:Honoraria, Other: consultancy or advisory role .
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- 2020
22. 621P Pembrolizumab (pembro) plus olaparib in patients (pts) with docetaxel-pretreated metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-365 Cohort A update
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Evan Y. Yu, Michael Paul Kolinsky, Peter C.C. Fong, Tilman Todenhöfer, J.S. de Bono, Josep M. Piulats, J.A. Arranz Arija, Stéphane Oudard, Audrey E. Kam, Ping Qiu, Ali Tafreshi, Howard Gurney, Nataliya Mar, Haiyan Wu, Charles Schloss, William R. Berry, Marinela Augustin, B. Laguerre, Margitta Retz, and G. Gravis
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Oncology ,medicine.medical_specialty ,business.industry ,Hematology ,Pembrolizumab ,Castration resistant ,medicine.disease ,Olaparib ,chemistry.chemical_compound ,Prostate cancer ,chemistry ,Docetaxel ,Internal medicine ,Cohort ,medicine ,In patient ,business ,medicine.drug - Published
- 2020
23. Pembrolizumab (pembro) plus olaparib in docetaxel-pretreated patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-365 cohort A updated results
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Peter C.C. Fong, Christian Heinrich Poehlein, Charles Schloss, Margitta Retz, Stéphane Oudard, Howard Gurney, Susan Feyerabend, William R. Berry, G. Gravis, Nataliya Mar, B. Laguerre, Evan Y. Yu, Ali Tafreshi, Josep M. Piulats, J. De Bono, Audrey E. Kam, J. A. Arranz, Heshui Wu, Marinela Augustin, and Michael Paul Kolinsky
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Urology ,Pembrolizumab ,Castration resistant ,lcsh:Diseases of the genitourinary system. Urology ,lcsh:RC870-923 ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,lcsh:RC254-282 ,Olaparib ,chemistry.chemical_compound ,Prostate cancer ,Docetaxel ,chemistry ,Internal medicine ,Cohort ,medicine ,business ,medicine.drug - Published
- 2020
24. Community-driven development of a modified progression-free survival ratio for precision oncology
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Andreas Mock, Christoph E Heilig, Simon Kreutzfeldt, Daniel Huebschmann, Christoph Heining, Evelin Schröck, Benedikt Brors, Albrecht Stenzinger, Dirk Jäger, Richard Schlenk, Hanno Glimm, Stefan Fröhling, Peter Horak, Leonidas Apostolidis, Marinela Augustin, Daniela Aust, Irfan Ahmed Bhatti, Johannes Bloehdorn, Cornelia Brendel, Christian Britschgi, Jan Braess, Stefan Burdach, Elena Busch, Jozefina Casuscelli, Alexander Desuki, Thomas Deutsch, Mareike Dietrich, Ursula Ehmer, Thomas J Ettrich, Johanna Falkenhorst, Tanja Fehm, Anne Flörcken, Andrea Forschner, Stefan Fuxius, Maria Gonzales-Carmona, Frank Griesinger, Sabine Grill, Stefan Gröschel, Georg Martin Haag, Ulrich Haag, Niels Halama, Holger Hebart, Nina Heidger, Barbara Hermes, Georg Hess, Simone Hettmer, Manuela Hoechstetter, Martin Hoffmann, Felix J Hüttner, Anna L Illert, Maximilian Jenzer, Bernd Kasper, Stefan Kasper-Virchow, Thomas Kindler, Ewa Koscielniak, Jan Krönke, Michael Kühn, Volker Kunzmann, Alois Lang, Jonas Leichsenring, Elisabeth Livingstone, Lucia Liotta, Kim Luley, Elisabeth Mack, Uwe M Martens, Klaus Metzeler, Jan Moritz Middeke, Lino Möhrmann, Roopa Jayarama-Naidu, Ulrich-Frank Pape, Lukas Perkhofer, Arne Pfeufer, Constantin Pixberg, Michael Quante, Bernhard Rendenbach, Damian Rieke, Christian Rothermundt, Andre Norbert Sagerer, Martin Salzmann, Dieter Saur, Bastian Schilling, Jan Schleicher, Anke Schlenska-Lange, Thomas Schmidt, Sophia Schmitz, Sebastian Schölch, Rajiv Shah, Khalid Shoumariyeh, Alexander Siebenhüner, Martin Singh, Jens Siveke, Christoph Springfeld, Helen Starke, Sophia Strobel, Veronica Teleanu, Niklas Thon, Sebastian Wagner, Thomas Walle, Benedikt Westphalen, Bettina Whitlock, Eva Winkler, Naita Maren Wirsik, Lena Woydack, Angelika Zabel-du Bois, Stefanie Zschäbitz, University of Zurich, and Fröhling, Stefan
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Oncology ,Cancer Research ,medicine.medical_specialty ,Concordance ,610 Medicine & health ,Classification scheme ,Medical Oncology ,Systemic therapy ,lcsh:RC254-282 ,PFS ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Neoplasms ,Antineoplastic Combined Chemotherapy Protocols ,Outcome Assessment, Health Care ,Clinical endpoint ,Medicine ,Humans ,1306 Cancer Research ,Progression-free survival ,Precision Medicine ,Societies, Medical ,030304 developmental biology ,Original Research ,Oncologists ,0303 health sciences ,Clinical Trials as Topic ,business.industry ,High-Throughput Nucleotide Sequencing ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,personalized oncology ,Progression-Free Survival ,3. Good health ,Precision oncology ,Research Design ,030220 oncology & carcinogenesis ,10032 Clinic for Oncology and Hematology ,Personalized oncology ,N-of-1 clinical trials ,2730 Oncology ,Outcome data ,business - Abstract
Objective Measuring the success of molecularly guided therapies is a major challenge in precision oncology trials. A commonly used endpoint is an intra-patient progression-free survival (PFS) ratio, defined as the PFS interval associated with molecularly guided therapy (PFS2) divided by the PFS interval associated with the last prior systemic therapy (PFS1), above 1.3 or, in some studies, above 1.33 or 1.5. Methods To investigate if the concept of PFS ratios is in agreement with actual response evaluations by physicians, we conducted a survey among members of the MASTER (Molecularly Aided Stratification for Tumor Eradication Research) Programme of the German Cancer Consortium who were asked to classify the success of molecularly guided therapies in 194 patients enrolled in the MOSCATO 01 trial based on PFS1 and PFS2 times. Results A comparison of classification profiles revealed three distinct clusters of PFS benefit assessments. Only 29% of assessments were consistent with a PFS ratio threshold of 1.3, whereas the remaining 71% of participants applied a different classification scheme that did not rely on the relation between PFS times alone, but also took into account absolute PFS1 intervals. Based on these community-driven insights, we developed a modified PFS ratio that incorporates the influence of absolute PFS1 intervals on the judgement of clinical benefit by physicians. Application of the modified PFS ratio to outcome data from two recent precision oncology trials, MOSCATO 01 and WINTHER, revealed significantly improved concordance with physician-perceived clinical benefit and identified comparable proportions of patients who benefited from molecularly guided therapies. Conclusions The modified PFS ratio may represent a meaningful clinical endpoint that could aid in the design and interpretation of future precision oncology trials.
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- 2019
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25. 217O Pembrolizumab (pembro) combination therapies in patients with metastatic castration-resistant prostate cancer (mCRPC): Cohorts A-C of the phase Ib/II KEYNOTE-365 study
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Josep M. Piulats, Henry Jacob Conter, Howard Gurney, Srikala S. Sridhar, William R. Berry, Evan Y. Yu, Michael Paul Kolinsky, Emanuela Romano, Charles Schloss, N.D. Shore, Haiyan Wu, Marinela Augustin, Christian Heinrich Poehlein, Margitta Retz, Peter C.C. Fong, Leonard Joseph Appleman, Anthony M. Joshua, Tilman Todenhöfer, Ali Tafreshi, and J.S. de Bono
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Oncology ,medicine.medical_specialty ,Prostate cancer ,business.industry ,Internal medicine ,Medicine ,In patient ,Hematology ,Pembrolizumab ,Castration resistant ,business ,medicine.disease - Published
- 2020
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