Phosphatidylinositol 3-Kinase Inhibition by Copanlisib in Relapsed or Refractory Indolent Lymphoma
| Autor: | 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 |
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| Přispěvatelé: | 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, Zinzani, Pier Luigi |
| Rok vydání: | 2017 |
| Předmět: |
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 |
| Zdroj: | Journal of Clinical Oncology. 35:3898-3905 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2017.75.4648 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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