Phase II evaluation of copanlisib, a selective inhibitor of Pi3kca, in patients with persistent or recurrent endometrial carcinoma harboring PIK3CA hotspot mutations: An NRG Oncology study (NRG-GY008).

Autor:	Santin AD; Department of Obstetrics, Gynecology & Reproductive Services, Yale University School of Medicine, New Haven, CT 06520, USA., Filiaci V; NRG Oncology Statistical and Data Management Center, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA., Bellone S; Department of Obstetrics, Gynecology & Reproductive Services, Yale University School of Medicine, New Haven, CT 06520, USA., Ratner ES; Department of Obstetrics, Gynecology & Reproductive Services, Yale University School of Medicine, New Haven, CT 06520, USA., Mathews CA; Medical Oncology, Women & Infants Hospital, 101 Dudley Street, Providence, RI 02905, USA., Cantuaria G; Gynecologic Oncology, 980 Johnson Ferry Road #910, Atlanta, GA 30342, USA., Gunderson CC; Department of Obstetrics & Gynecology, University of Oklahoma, The Stephenson Cancer Center, 800 NE 10 Street, Suite 2500, Oklahoma City, OK 73104, USA., Rutledge T; Gynecologic Oncology, University of New Mexico, 1201 Camino de Salud, Albuquerque, NM 87102, USA., Buttin BM; Department of Obstetrics & Gynecology, Northwestern Medicine Regional Medical Group, 4405 Weaver Parkway, Warrenville, IL 60555-3269, USA., Lankes HA; NRG Oncology, Operations Center-Philadelphia East, Philadelphia, PA, USA.; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, Columbus, OH, USA., Frumovitz M; Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA., Khleif SN; Director, The Loop Immuno-Oncology Research Laboratory, Lombardi Cancer Center, Georgetown University, Washington, DC 20057, USA., Huh WK; Division of Gynecologic Oncology, University of Alabama at Birmingham, Birmingham AL 35205, USA., Birrer MJ; Division of Hematology/Oncology, O'Neal Cancer Center University of Alabama, 176F 10390, 619 19 Street S, Birmingham, AL, USA.
Jazyk:	angličtina
Zdroj:	Gynecologic oncology reports [Gynecol Oncol Rep] 2020 Jan 02; Vol. 31, pp. 100532. Date of Electronic Publication: 2020 Jan 02 (Print Publication: 2020).
DOI:	10.1016/j.gore.2019.100532
Abstrakt:	Purpose: NRG Oncology conducted a phase II trial to assess the antitumor activity and tolerability of copanlisib, a selective inhibitor of PIK3CA, in persistent or recurrent endometrial carcinoma harboring hotspot PIK3CA mutations. Patients and Methods: Eligible patients had endometrial cancer with endometrioid, serous or mixed histology, a somatic PIK3CA gene mutation, measurable disease, and GOG performance status ≤2. Treatment consisted of IV copanlisib (60 mg weekly, day 1, 8 and 15 of 28-day cycle) until disease progression or prohibitive toxicity. The primary endpoints of the study were objective tumor response as assessed by RECIST 1.1 and to determine the nature and degree of toxicity of copanlisib as assessed by CTCAE version 4. The study used a 2-stage group sequential design. Results: Eleven patients were enrolled onto stage I of the treatment trial. Five patients had endometrioid, four serous and two had a tumor of mixed histology. The most common PIK3CA mutation was Q546X (n = 3) in exon 9. The most common grade 3 or 4 AE was hyperglycemia. No grade 5 adverse events were reported. No clinical responses were detected. Six patients had a best overall response of stable disease. Of 11 who initiated treatment, 10 progressed on treatment. One patient with stable disease on copanlisib withdrew from treatment secondary to relocation. The median progression-free survival (PFS) was 2.8 months; at 6 months 27% were alive, progression-free. The median overall survival (OS) was 15.2 months. Due to the lack of CR/PR continuation of accrual to the second stage of accrual was not warranted. Conclusion: Copanlisib is well tolerated but has limited activity as a single agent in this population. Competing Interests: Dr. Santin received research grants from Puma, Immunomedics, Gilead, Synthon, Merck, Boehringer-Ingelheim, Genentech and Tesaro and consulting fees from Merck and Tesaro. Dr. Filiaci reports grants from NIH, during the conduct of the study as well as grants from the GOG Foundation, outside of the submitted work. Dr. O’Cearbhaill reports personal fees from Clovis, personal fees from Tesaro, personal fees from GlaxoSmithKline, outside of the submitted work. Dr. Ratner reports other support received for serving on the Tesaro Advisory Board as well as the Genentech Advisory board which she wishes to disclose. Dr. Mathews reports grants from National Cancer Institute, during the conduct of the study. Dr. Gunderson reports other from Clovis, other from Cordgenics, other from Agenus, outside of the submitted work. All other co-authors have no conflicts of interest to disclose. (© 2020 The Authors.)
Databáze:	MEDLINE
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