التفاصيل البيبلوغرافية
العنوان:
A multicenter, single-arm, open-label, phase 2 study of apitolisib (GDC-0980) for the treatment of recurrent or persistent endometrial carcinoma (MAGGIE study)
المؤلفون:
Carol Aghajanian , Yulei Wang , Jill M. Spoerke , Shan Lu , Ling-Yuh Huw , Ursula A. Matulonis , Rui Zhu , Vicky Makker , Houston Gilbert , Hema Parmar , Ling Ma , Fernando O. Recio , Mark R. Lackner , Joseph A. Ware , Jennifer O. Lauchle , Hartmut Koeppen
المصدر:
Cancer . 122:3519-3528
بيانات النشر:
Wiley, 2016.
سنة النشر:
2016
مصطلحات موضوعية:
0301 basic medicine , Cancer Research , medicine.medical_specialty , business.industry , Endometrial cancer , Phases of clinical research , Common Terminology Criteria for Adverse Events , medicine.disease , Rash , Gastroenterology , Surgery , Discontinuation , 03 medical and health sciences , 030104 developmental biology , 0302 clinical medicine , Oncology , Tolerability , 030220 oncology & carcinogenesis , Internal medicine , medicine , Carcinoma , medicine.symptom , business , Adverse effect
الوصف:
BACKGROUND The current single-arm, open-label trial was designed to evaluate the activity of apitolisib (GDC-0980), a dual phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor, in patients with advanced endometrial cancer (EC). METHODS Patients with recurrent or persistent EC who were treated with 1 to 2 prior lines of chemotherapy but no prior PI3K/mTOR inhibitor received oral apitolisib at a dose of 40 mg daily during 28-day cycles until disease progression or intolerable toxicity occurred. Patients with type I/II diabetes who required insulin were excluded. The primary endpoints were progression-free survival (PFS) at 6 months and objective response rate. RESULTS A total of 56 women were enrolled, including 13 (23%) with well-controlled diabetes. Reasons for discontinuation were disease progression (24 patients; 43%), adverse events (13 patients; 23%), and withdrawal by subject (12 patients; 21%). Grade 3/4 apitolisib-related adverse events were hyperglycemia (46%), rash (30%), colitis (5%), and pneumonitis (4%) (toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). The PFS rate at 6 months was 20% (Kaplan-Meier estimate; 95% confidence interval [95% CI], 7%-33%). The objective response rate was 6% (confirmed). The median PFS was 3.5 months (95% CI, 2.7-3.7 months) and the median overall survival was 15.7 months (95% CI, 9.2-17.0 months). Nineteen patients discontinued the study before the first tumor assessment. Dose reductions were required for 4 diabetic (31%) and 18 nondiabetic (42%) patients. Comprehensive molecular profiling of 46 evaluable archival tumor samples demonstrated that 57% of patients had at least 1 alteration in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphatase and tensin homolog (PTEN), or AKT1. All 3 patients with a confirmed response had at least 1 alteration in a PI3K pathway gene. CONCLUSIONS The antitumor activity noted with the use of a dose of 40 mg of apitolisib daily was limited by tolerability, especially in diabetic patients. Patients with PI3K pathway mutations may have derived enhanced benefit from apitolisib. Cancer 2016. © 2016 American Cancer Society.
تدمد:
0008-543X
DOI:
10.1002/cncr.30286
URL الوصول:
https://explore.openaire.eu/search/publication?articleId=doi_________::5d33de98628b96ee8ea339b75a6df36d https://doi.org/10.1002/cncr.30286
Rights:
OPEN
رقم الانضمام:
edsair.doi...........5d33de98628b96ee8ea339b75a6df36d
قاعدة البيانات:
OpenAIRE