3 results on '"Garcia-Vargas, Jose"'
Search Results
2. Long-term safety and efficacy of the PI3K inhibitor copanlisib in patients with relapsed or refractory indolent lymphoma: 2-year follow-up of the CHRONOS-1 study
- Author
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Pier Luigi Zinzani, Maria Dimou, J. Garcia-Vargas, Arnon Nagler, Judit Demeter, Sirpa Leppä, Liana Rodrigues, Georg Lenz, Muhit Ozcan, Javier Munoz, Luigina Mollica, David Trevarthen, George A Follows, Barrett H. Childs, Florian Hiemeyer, Franck Morschhauser, Marina Kosinova, Ashok Miriyala, Armando Santoro, Won Seog Kim, Martin Dreyling, Krimo Bouabdallah, Don A. Stevens, Dreyling, Martin, Santoro, Armando, Mollica, Luigina, Leppä, Sirpa, Follows, George, Lenz, Georg, Kim, Won Seog, Nagler, Arnon, Dimou, Maria, Demeter, Judit, Özcan, Muhit, Kosinova, Marina, Bouabdallah, Krimo, Morschhauser, Franck, Stevens, Don A, Trevarthen, David, Munoz, Javier, Rodrigues, Liana, Hiemeyer, Florian, Miriyala, Ashok, Garcia-Vargas, Jose, Childs, Barrett H, Zinzani, Pier Luigi, Department of Oncology, HUS Comprehensive Cancer Center, Doctoral Programme in Clinical Research, Doctoral Programme in Biomedicine, Sirpa Marianne Leppä / Principal Investigator, Clinicum, and Research Programs Unit
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Male ,Follicular lymphoma ,Gastroenterology ,chemistry.chemical_compound ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Multicenter Studies as Topic ,Medicine ,IDELALISIB ,Phosphoinositide-3 Kinase Inhibitors ,Aged, 80 and over ,0303 health sciences ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Allografts ,Combined Modality Therapy ,Progression-Free Survival ,3. Good health ,PI3K-DELTA ,BAY 80-6946 ,Treatment Outcome ,030220 oncology & carcinogenesis ,Hypertension ,Female ,Adult ,Diarrhea ,medicine.medical_specialty ,Lymphoma, B-Cell ,Neutropenia ,PHOSPHATIDYLINOSITOL 3-KINASE INHIBITION ,3122 Cancers ,PI3K inhibitor, copanlisib, indolent lymphoma ,Transplantation, Autologous ,Drug Administration Schedule ,03 medical and health sciences ,Clinical Trials, Phase II as Topic ,Internal medicine ,Humans ,DOSE-ESCALATION ,Progression-free survival ,Adverse effect ,Survival analysis ,Aged ,030304 developmental biology ,Copanlisib ,Pneumonitis ,Salvage Therapy ,business.industry ,ALPELISIB ,PHASE IB ,medicine.disease ,Survival Analysis ,Transplantation ,Pyrimidines ,chemistry ,P110-ALPHA ,Hyperglycemia ,Quinazolines ,business ,Follow-Up Studies ,BUPARLISIB - Abstract
Safety profiles of oral PI3K inhibitors have resulted in US FDA black box warnings regarding fatal/serious toxicities. The approved intravenous PI3K inhibitor copanlisib has low incidence of severe toxicities and no black box warnings, but chronic treatment effects were unknown. We provide an update on safety and efficacy of copanlisib with a minimum 2-year follow-up of the CHRONOS-1 study. A total of 142 patients with histologically confirmed indolent B-cell lymphoma who had relapsed after or were refractory to >= 2 prior treatments received intravenous copanlisib 60 mg on days 1, 8, and 15 (28-day cycle). The primary efficacy endpoint was objective response rate (ORR) after >= 4 cycles (independent assessment). The predominant histology was follicular lymphoma (n = 104). The ORR was 60.6% (seven additional complete responses since primary analysis). Secondary endpoints of median duration of response, progression-free survival, and overall survival were 14.1 months (median follow-up, 16.1 months), 12.5 months (median follow-up, 14.0 months), and 42.6 months (median follow-up, 31.5 months), respectively. Median safety follow-up was 6.7 months; 26% of patients received treatment for >1 year. Common treatment-emergent adverse events (TEAEs) (all grade/grade 3/grade 4) were transient hyperglycemia (50.0%/33.1%/7.0%), diarrhea (35.2%/8.5%/0%), transient hypertension (29.6%/23.9%/0%), and neutropenia (28.9%/9.2%/14.8%). Serious AEs were largely unchanged, with no new cases of pneumonitis (4.2%), diarrhea (2.8%), or grade 5 events. Note, TEAEs showed no evidence for increased incidence or worsening following longer exposure in patients treated >1 year. Long-term follow-up of patients with relapsed/refractory indolent B-cell lymphoma treated with intravenous copanlisib demonstrated durable, enhanced responses without evidence of worsening TEAEs, as reported for orally administered PI3K inhibitors.
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- 2020
3. Phosphatidylinositol 3-Kinase Inhibition by Copanlisib in Relapsed or Refractory Indolent Lymphoma
- Author
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Judit Demeter, Henrik Seidel, Barrett H. Childs, Krimo Bouabdallah, Pier Luigi Zinzani, J. Garcia-Vargas, Don A. Stevens, Won Seog Kim, Karl Köchert, George A. Follows, Georg Lenz, Muhit Ozcan, Martin Dreyling, Panayiotis Panayiotidis, Lisa Cupit, Marius Giurescu, Franck Morschhauser, Armando Santoro, Marina Kosinova, Carol Peña, Luigina Mollica, Florian Hiemeyer, Shuxin Yin, David Trevarthen, Sirpa Leppä, Arnon Nagler, Li Liu, Dreyling, Martin, Santoro, Armando, Mollica, Luigina, Leppä, Sirpa, Follows, George A, Lenz, Georg, Kim, Won Seog, Nagler, Arnon, Panayiotidis, Panayioti, Demeter, Judit, Özcan, Muhit, Kosinova, Marina, Bouabdallah, Krimo, Morschhauser, Franck, Stevens, Don A, Trevarthen, David, Giurescu, Mariu, Cupit, Lisa, Liu, Li, Köchert, Karl, Seidel, Henrik, Peña, Carol, Yin, Shuxin, Hiemeyer, Florian, Garcia-Vargas, Jose, Childs, Barrett H, and Zinzani, Pier Luigi
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Adult ,Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lymphoma, B-Cell ,Protein Kinase Inhibitor ,Phases of clinical research ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Refractory ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Phosphatidylinositol ,Protein Kinase Inhibitors ,Phosphoinositide-3 Kinase Inhibitors ,Aged ,Copanlisib ,Aged, 80 and over ,Errata ,business.industry ,Quinazoline ,Middle Aged ,medicine.disease ,Duvelisib ,Isoenzyme ,Lymphoma ,Isoenzymes ,Clinical trial ,Pyrimidines ,030104 developmental biology ,Pyrimidine ,chemistry ,030220 oncology & carcinogenesis ,Immunology ,Quinazolines ,Female ,Phosphatidylinositol 3-Kinase ,Transcriptome ,business ,Human - Abstract
Purpose Phosphatidylinositol 3-kinase (PI3K) signaling is critical for the proliferation and survival of malignant B cells. Copanlisib, a pan-class I PI3K inhibitor with predominant activity against PI3K-α and -δ isoforms, has demonstrated efficacy and a manageable safety profile in patients with indolent lymphoma. Patients and Methods In this phase II study, 142 patients with relapsed or refractory indolent lymphoma after two or more lines of therapy were enrolled to receive copanlisib 60 mg intravenously on days 1, 8, and 15 of a 28-day cycle. The primary end point was objective response rate; secondary end points included duration of response, progression-free survival, and overall survival. In addition, safety and gene expression were evaluated. Results Median age was 63 years (range, 25 to 82 years), and patients had received a median of three (range, two to nine) prior regimens. The objective response rate was 59% (84 of 142 patients); 12% of patients achieved a complete response. Median time to response was 53 days. Median duration of response was 22.6 months, median progression-free survival was 11.2 months, and median overall survival had not yet been reached. The most frequent treatment-emergent adverse events were transient hyperglycemia (all grades, 50%; grade 3 or 4, 41%) and transient hypertension (all grades, 30%; grade 3, 24%). Other grade ≥3 events included decreased neutrophil count (24%) and lung infection (15%). High response rates to copanlisib were associated with high expression of PI3K/B-cell receptor signaling pathway genes. Conclusion PI3K-α and -δ inhibition by copanlisib demonstrated significant efficacy and a manageable safety profile in heavily pretreated patients with relapsed or refractory indolent lymphoma.
- Published
- 2017
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