Title :

Phosphatidylinositol 3-Kinase Inhibition by Copanlisib in Relapsed or Refractory Indolent Lymphoma

Author(s) :

Dreyling, Martin [Auteur]
Santoro, Armando [Auteur]
Mollica, Luigina [Auteur]
Leppa, Sirpa [Auteur]
Follows George, A [Auteur]
Lenz, Georg [Auteur]
Kim Won, Seog [Auteur]
Nagler, Arnon [Auteur]
Panayiotidis, Panayiotis [Auteur]
Demeter, Judit [Auteur]
Ozcan, Muhit [Auteur]
Kosinova, Marina [Auteur]
Bouabdallah, Krimo [Auteur]
Morschhauser, Franck [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Stevens Don, A [Auteur]
Trevarthen, David [Auteur]
Giurescu, Marius [Auteur]
Cupit, Lisa [Auteur]
Liu, Li [Auteur]
Koechert, Karl [Auteur]
Seidel, Henrik [Auteur]
Pena, Carol [Auteur]
Yin, Shuxin [Auteur]
Hiemeyer, Florian [Auteur]
Garcia-Vargas, Jose [Auteur]
Childs Barrett, H [Auteur]
Zinzani Pier, Luigi [Auteur]

Journal title :

Journal of clinical oncology

Abbreviated title :

J. Clin. Oncol.

Volume number :

35

Pages :

3898-+

Publication date :

2017

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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, ...
Show more >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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CHU Lille

Collections :

• Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365

Research team(s) :

Innovation/évaluation des médicaments injectables

Submission date :

2019-02-26T17:07:05Z