Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma.
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Date
2017-09Author
Dreyling, M
Morschhauser, F
Bouabdallah, K
Bron, D
Cunningham, D
Assouline, SE
Verhoef, G
Linton, K
Thieblemont, C
Vitolo, U
Hiemeyer, F
Giurescu, M
Garcia-Vargas, J
Gorbatchevsky, I
Liu, L
Koechert, K
Peña, C
Neves, M
Childs, BH
Zinzani, PL
Type
Journal Article
Metadata
Show full item recordAbstract
Background Copanlisib is a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α- and δ-isoforms.Patients and methods This phase II study evaluated the response rate of copanlisib administered intravenously on days 1, 8, and 15 of a 28-day cycle, in patients with indolent or aggressive malignant lymphoma. Archival tumor tissues were used for immunohistochemistry, gene-expression profiling, and mutation analysis.Results Thirty-three patients with indolent lymphoma and 51 with aggressive lymphoma received copanlisib. Follicular lymphoma (48.5%) and peripheral T-cell lymphoma (33.3%) were the most common histologic subtypes. Most patients (78.6%) had received prior rituximab and 54.8% were rituximab-refractory. Median duration of treatment was 23 and 8 weeks in the indolent and aggressive cohorts, respectively (overall range 2-138). Eighty patients were evaluated for efficacy. The objective response rate was 43.7% (14/32) in the indolent cohort and 27.1% (13/48) in the aggressive cohort; median progression-free survival was 294 days (range 0-874) and 70 days (range 0-897), respectively; median duration of response was 390 days (range 0-825) and 166 days (range 0-786), respectively. Common adverse events included hyperglycemia (57.1%; grade ≥3, 23.8%), hypertension (54.8%; grade ≥3, 40.5%), and diarrhea (40.5%; grade ≥3, 4.8%), all generally manageable. Neutropenia occurred in 28.6% of patients (grade 4, 11.9%). Molecular analyses showed enhanced antitumor activity in tumors with upregulated phosphatidylinositol 3-kinase pathway gene expression.Conclusion Intravenous copanlisib demonstrated promising efficacy and manageable toxicity in heavily pretreated patients with various subtypes of indolent and aggressive malignant lymphoma. Subtype-specific studies of copanlisib in patients with follicular, peripheral T-cell, and mantle cell lymphomas are ongoing. This trial is registered with ClinicalTrials.gov number NCT01660451 (Part A).
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Subject
Humans
Lymphoma
Recurrence
Pyrimidines
Quinazolines
Antineoplastic Agents
Survival Analysis
Aged
Aged, 80 and over
Middle Aged
Female
Male
PTEN Phosphohydrolase
Biomarkers, Tumor
Phosphoinositide-3 Kinase Inhibitors
Research team
Medicine (RMH Smith Cunningham)
Language
eng
License start date
2017-09
Citation
Annals of oncology : official journal of the European Society for Medical Oncology, 2017, 28 (9), pp. 2169 - 2178