A multicenter, single-arm, open-label, phase 2 study of apitolisib (GDC-0980) for the treatment of recurrent or persistent endometrial carcinoma (MAGGIE study).
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;122:3519-28. © 2016 American Cancer Society.
Gynecologic Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York.|Weill Cornell Medical College, New York, New York.
Vicky
V
Makker
South Florida Center for Gynecologic Oncology, Boca Raton, Florida.
Fernando O
FO
Recio
Rocky Mountain Cancer Centers, Lakewood, Colorado.
Ling
L
Ma
Dana-Farber Cancer Institute, Boston, Massachusetts.
Ursula A
UA
Matulonis
Genentech Inc, South San Francisco, California.
Jennifer O
JO
Lauchle
Genentech Inc, South San Francisco, California.
Hema
H
Parmar
Genentech Inc, South San Francisco, California.
Houston N
HN
Gilbert
Genentech Inc, South San Francisco, California.
Joseph A
JA
Ware
Genentech Inc, South San Francisco, California.
Rui
R
Zhu
Genentech Inc, South San Francisco, California.
Shan
S
Lu
Genentech Inc, South San Francisco, California.
Ling-Yuh
LY
Huw
Genentech Inc, South San Francisco, California.
Yulei
Y
Wang
Genentech Inc, South San Francisco, California.
Hartmut
H
Koeppen
Genentech Inc, South San Francisco, California.
Jill M
JM
Spoerke
Genentech Inc, South San Francisco, California.
Mark R
MR
Lackner
Gynecologic Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York.|Weill Cornell Medical College, New York, New York.
Carol A
CA
Aghajanian
GDC-0980; MAGGIE; apitolisib; endometrial cancer