Combination treatment of copanlisib and gemcitabine in relapsed/refractory PTCL (COSMOS): an open-label phase I/II trial
- Authors
- Yhim, H.-Y.; Kim, T.; Kim, S.J.; Shin, H.-J.; Koh, Y.; Kim, J.S.; Park, J.; Park, G.S.; Kim, W.S.; Moon, J.H.; Yang, D.-H.
- Issue Date
- Apr-2021
- Publisher
- ELSEVIER
- Keywords
- copanlisib; gemcitabine; peripheral T-cell lymphoma; phase I/II trial; relapsed or refractory
- Citation
- Annals of Oncology, v.32, no.4, pp.552 - 559
- Journal Title
- Annals of Oncology
- Volume
- 32
- Number
- 4
- Start Page
- 552
- End Page
- 559
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/80672
- DOI
- 10.1016/j.annonc.2020.12.009
- ISSN
- 0923-7534
- 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. © 2020 European Society for Medical Oncology
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