Prospective phase II trial of everolimus in PIK3CA amplification/mutation and/or PTEN loss patients with advanced solid tumors refractory to standard therapy

BMC Cancer

Research Article

Young Suk Park¹  Jeeyun Lee¹  Ho Yeong Lim¹  Se Hoon Park¹  Won Ki Kang¹  Seung Tae Kim¹  Joon Oh Park¹ 

[1] Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro Gangnam-gu, 135-710, Seoul, Korea;

关键词: PIK3CA amplification/mutation;    PTEN loss;    everolimus;   

DOI  :  10.1186/s12885-017-3196-6

 received in 2016-04-05, accepted in 2017-03-14,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundWe designed a single-arm, open-label phase II trial of everolimus in PIK3CA amplification/mutation and/or PTEN loss patients with advanced solid tumors refractory to standard therapy (#NCT02449538).MethodsEverolimus was administered orally at a daily dose of 10 mg continuously (28-day cycles). Treatment was continued until progression of the disease or intolerable toxicity was observed. Based on Simon’s two-stage optimal design, 10 patients were treated with everolimus during the first stage.ResultsThe median age of the patients was 55.5 years (range, 42–72), and the median Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 2 (range, 1–2). Most of the patients (50.0%) had gastric cancer (GC) as the site of their primary tumor followed by colorectal cancer (CRC), pancreatic cancer, and cholangiocarcinoma. Patients received everolimus as a third-line (3 patients), fourth-line (4 patients), fifth-line (1 patient) or sixth-line (2 patients) treatment. Complete or partial responses were not observed in any of the patients. Four patients showed stable disease, resulting in a disease control rate of 40%. The median PFS was 1.6 months (95% CI, 0.8–2.4 months). Grade 3 or greater hematologic/non-hematologic toxicity was not observed. Grade 2 diarrhea and stomatitis were reported in one patient each. There were no treatment-related deaths. There was less than one response out of the 10 initial patients during the first stage, and the study did not progress to the second stage.ConclusionsThe study did not meet its primary objective of demonstrating the anti-tumor activity of everolimus in PIK3CA amplification/mutation and/or PTEN loss patients with advanced solid tumors refractory to standard therapy. Further investigation using other genomic candidates and new-generation mTOR inhibitors is warranted in patients with treatment-refractory cancer.Trial registration#NCT02449538, April 2015.

【 授权许可】

CC BY   
© The Author(s). 2017