期刊
ANNALS OF ONCOLOGY
卷 32, 期 4, 页码 552-559出版社
ELSEVIER
DOI: 10.1016/j.annonc.2020.12.009
关键词
copanlisib; gemcitabine; peripheral T-cell lymphoma; relapsed or refractory; phase I/II trial
类别
资金
- Bayer HealthCare Pharmaceuticals, Inc.
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HR20C0021]
The combination of copanlisib and gemcitabine showed good safety and efficacy in patients with relapsed/refractory PTCL, with an overall response rate of 72% and a complete response rate of 32%, along with a significant extension in progression-free survival.
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-alpha/-delta 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/m(2) 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.
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