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Combination treatment of copanlisib and gemcitabine in relapsed/refractory PTCL (COSMOS): an open-label phase I/II trial

Authors
 H-Y Yhim  ;  T Kim  ;  S J Kim  ;  H-J Shin  ;  Y Koh  ;  J S Kim  ;  J Park  ;  G S Park  ;  W S Kim  ;  J H Moon  ;  D-H Yang 
Citation
 ANNALS OF ONCOLOGY, Vol.32(4) : 552-559, 2021-04 
Journal Title
ANNALS OF ONCOLOGY
ISSN
 0923-7534 
Issue Date
2021-04
MeSH
Deoxycytidine / analogs & derivatives ; Humans ; Lymphoma, T-Cell, Peripheral* ; Neoplasm Recurrence, Local / drug therapy ; Pyrimidines ; Quinazolines ; Treatment Outcome
Keywords
copanlisib ; gemcitabine ; peripheral T-cell lymphoma ; phase I/II trial ; relapsed or refractory
Abstract
Background: Current treatment options for peripheral T-cell lymphomas (PTCLs) in the relapsed/refractory setting are limited and demonstrate modest response rates with rare achievement of complete response (CR).

Patients and methods: This phase I/II study (NCT03052933) investigated the safety and efficacy of copanlisib, a phosphatidylinositol 3-kinase-α/-δ inhibitor, in combination with gemcitabine in 28 patients with relapsed/refractory PTCL. Patients received escalating doses of intravenous copanlisib on days 1, 8, and 15, administered concomitantly with fixed-dose gemcitabine (1000 mg/m2 on days 1 and 8) in 28-day cycles.

Results: Dose-limiting toxicity was not observed in the dose-escalation phase and 60 mg copanlisib was selected for phase II evaluation. Twenty-five patients were enrolled in phase II of the study. Frequent grade ≥3 adverse events (AEs) included transient hyperglycemia (57%), neutropenia (45%), thrombocytopenia, (37%), and transient hypertension (19%). However, AEs were manageable, and none were fatal. The overall response rate was 72% with a CR rate of 32%. Median duration of response was 8.2 months, progression-free survival was 6.9 months, and median overall survival was not reached. Combination treatment produced a greater CR rate in patients with angioimmunoblastic T-cell lymphoma than those with PTCL-not otherwise specified (55.6% versus 15.4%, respectively, P = 0.074) and progression-free survival was significantly longer (13.0 versus 5.1 months, respectively, P = 0.024). In an exploratory gene mutation analysis of 24 tumor samples, TSC2 mutation was present in 25% of patients and occurred exclusively in responders.

Conclusion: The combination of copanlisib and gemcitabine is a safe and effective treatment option in relapsed/refractory PTCLs and represents an important new option for therapy in this rare group of patients.
Files in This Item:
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DOI
10.1016/j.annonc.2020.12.009
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jin Seok(김진석) ORCID logo https://orcid.org/0000-0001-8986-8436
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/190393
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