A phase 2 study of alisertib (MLN8237) in recurrent or persistent uterine leiomyosarcoma: An NRG Oncology/Gynecologic Oncology Group study 0231D.

Autor: Hyman DM; Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: hymand@mskcc.org., Sill MW; NRG Oncology Statistics and Data Management Center, Buffalo, NY 14263, USA. Electronic address: msill@gogstats.org., Lankes HA; NRG Oncology Statistics and Data Management Center, Buffalo, NY 14263, USA. Electronic address: hlankes@gogstats.org., Piekarz R; Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: rpiekarz@nih.gov., Shahin MS; Abington Hospital, Jefferson Health, Abington, PA 19001, USA. Electronic address: mshahin@abingtonhealth.org., Ridgway MR; University of Mississippi Medical Center, Jackson, MS 39216, USA. Electronic address: mridgway@umc.edu., Backes F; Ohio State University, Wexner Medical Center, Hilliard, OH 43026, USA. Electronic address: Floor.Backes@osumc.edu., Tenney ME; Gynecologic Oncology, The University of Chicago Medicine & Biological Sciences, Chicago, IL 60637, USA. Electronic address: mtenney@bsd.uchicago.edu., Mathews CA; Women & Infants Hospital, Providence, RI 02905, USA. Electronic address: cmathews@wihri.org., Hoffman JS; Hospital of Central Connecticut, New Britain, CT 06050, USA. Electronic address: James.HoffmanMD@baystatehealth.org., Aghajanian C; Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: aghajanc@mskcc.org., Hensley ML; Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: hensleym@mskcc.org.
Jazyk: angličtina
Zdroj: Gynecologic oncology [Gynecol Oncol] 2017 Jan; Vol. 144 (1), pp. 96-100. Date of Electronic Publication: 2016 Oct 27.
DOI: 10.1016/j.ygyno.2016.10.036
Abstrakt: Objective: This two-stage Phase II study assessed the activity of single agent alisertib in patients with recurrent/persistent uterine leiomyosarcoma (uLMS).
Methods: Eligibility criteria included histologically-confirmed, recurrent or persistent uLMS, age≥18, 1-2 prior cytotoxic regimens, and RECIST version 1.1 measurable disease. The primary objective of the study was to evaluate the efficacy of alisertib through the frequency of patients with objective tumor responses and the frequency who survived event-free for at least 6months (EFS6). The endpoints for EFS were RECIST progression, death, or beginning a subsequent therapy. The null hypothesis jointly specified the probability of a patient experiencing a tumor response to less than or equal to 5% and the probability of a patient surviving event-free for at least 6months to less than or equal to 20%. A two-stage design was used with a target accrual of 23 patients for stage 1 and 47 pts. cumulative for stage 2. Confidence intervals do not correct for multiplicity.
Results: Twenty-three patients were enrolled with two patients excluded on central histology review, yielding 21 eligible patients. Median age was 61years. Prior treatment was either 1 cytotoxic regimen (71.4%) or 2 (28.6%). The most common treatment related AEs (grade 3 or worse) were anemia Hensley et al. (2008a) , leukopenia Hensley et al. (2008b) , neutropenia Maki et al. (2007) , thrombocytopenia Huang et al. (2012) , mucositis Hensley et al. (2008a) , diarrhea Huang et al. (2012) , and palmer-planter syndrome Zivanovic et al. (2012) . There were no objective responses (0%; 90% CI: 0-10.4%). Best response was stable disease (38.1%); 12 patients had progressive disease (57.1%). EFS6 was 0% (90% CI: 0-10.4%). Median PFS and OS were 1.7 (90% CI: 1.4-3.2) and 14.5months (90% CI: 7.6 - NA), respectively.
Conclusion: Alisertib did not demonstrate clinically meaningful single agent activity in previously treated uLMS.
Competing Interests: The authors report that there are no conflicts of interest to disclose other than Dr. Hyman who reports grants and non-financial support from PUMA Biotechnology, AstraZeneca and LOXO Oncology. He has also received personal fees from both CytomX and Atara Biotherapeutics and non –financial support from Roche/Genentech outside the submitted work. Additionally, Dr. Carol Aghajanian reports that she has received compensation from Oxigene for a one time Steering Committee meeting in 2016 as well as compensation for serving on a one time Advisory Board in 2014 for Astra Zeneca. Dr. Aghajanian was reimbursed for travel expenses by AbbVie in 2014.
(Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: