PMID- 33352201 OWN - NLM STAT- MEDLINE DCOM- 20210331 LR - 20221207 IS - 1569-8041 (Electronic) IS - 0923-7534 (Linking) VI - 32 IP - 4 DP - 2021 Apr TI - Combination treatment of copanlisib and gemcitabine in relapsed/refractory PTCL (COSMOS): an open-label phase I/II trial. PG - 552-559 LID - S0923-7534(20)43215-6 [pii] LID - 10.1016/j.annonc.2020.12.009 [doi] AB - 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. CI - Copyright (c) 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved. FAU - Yhim, H-Y AU - Yhim HY AD - Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Republic of Korea; Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea. FAU - Kim, T AU - Kim T AD - Department of Medical Sciences, Chonnam National University Medical School, Jeollanam-do, Republic of Korea. FAU - Kim, S J AU - Kim SJ AD - Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. FAU - Shin, H-J AU - Shin HJ AD - Department of Internal Medicine, Pusan National University Hospital, Busan, Republic of Korea. FAU - Koh, Y AU - Koh Y AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. FAU - Kim, J S AU - Kim JS AD - Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. FAU - Park, J AU - Park J AD - Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea. FAU - Park, G S AU - Park GS AD - Department of Pathology, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea. FAU - Kim, W S AU - Kim WS AD - Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. FAU - Moon, J H AU - Moon JH AD - Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address: jhmoon@knu.ac.kr. FAU - Yang, D-H AU - Yang DH AD - Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Jeollanam-do, Republic of Korea. Electronic address: drydh1685@hotmail.com. LA - eng PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201225 PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0 (Pyrimidines) RN - 0 (Quinazolines) RN - 0W860991D6 (Deoxycytidine) RN - WI6V529FZ9 (copanlisib) RN - 0 (Gemcitabine) SB - IM MH - Deoxycytidine/analogs & derivatives MH - Humans MH - *Lymphoma, T-Cell, Peripheral MH - Neoplasm Recurrence, Local/drug therapy MH - Pyrimidines MH - Quinazolines MH - Treatment Outcome MH - Gemcitabine OTO - NOTNLM OT - copanlisib OT - gemcitabine OT - peripheral T-cell lymphoma OT - phase I/II trial OT - relapsed or refractory COIS- Disclosure D-HY reports receipt of institutional research funding from Bayer HealthCare Pharmaceuticals, Inc. All remaining authors have declared no conflicts of interest. EDAT- 2020/12/23 06:00 MHDA- 2021/04/01 06:00 CRDT- 2020/12/22 20:08 PHST- 2020/10/01 00:00 [received] PHST- 2020/12/01 00:00 [revised] PHST- 2020/12/15 00:00 [accepted] PHST- 2020/12/23 06:00 [pubmed] PHST- 2021/04/01 06:00 [medline] PHST- 2020/12/22 20:08 [entrez] AID - S0923-7534(20)43215-6 [pii] AID - 10.1016/j.annonc.2020.12.009 [doi] PST - ppublish SO - Ann Oncol. 2021 Apr;32(4):552-559. doi: 10.1016/j.annonc.2020.12.009. Epub 2020 Dec 25.