br Results br Patient characteristics br Between th August a
3.1. Patient characteristics
Between 14th August 2013 and 19th December 2014, 153 patients were enrolled and randomised (S2). Patient characteristics were generally similar between treatment arms (Table 1). The proportion of patients with ECOG PS 1 was slightly higher in the placebo versus ipatasertib
Patient baseline demographics and clinical characteristics.
Ipatasertib þ Placebo þ
AJCC, American Joint Committee on Cancer; ECOG PS, Eastern Cooperative Oncology Group performance status; GEJ, gastroesoph-ageal junction; mFOLFOX6, modified regimen of leucovorin, 5-fluo-rouracil and oxaliplatin; PTEN, phosphatase and tensin homolog; SD, standard deviation. a ECOG PS data missing for 1 patient in placebo/mFOLFOX6 arm.
b n Z 81 for ipatasertib/mFOLFOX6.
As of the primary data cut-off (3rd June 2015), 64 patients (91.4%) had discontinued ipatasertib, and 73 patients (89%) had discontinued placebo; disease pro-gression was the most common reason (S2). The same proportion of patients in each group discontinued 5-FU (bolus and IV; S2). Four patients with response to study treatment discontinued early and subsequently under-went surgery with curative intent (1 in ipatasertib arm and 3 in placebo arm). Forty-seven patients (66.2%) in the ipatasertib arm and 34 (41.5%) in the placebo arm discontinued from the study survival follow-up, most commonly due to death. Mean treatment duration, dose intensity and dose modifications of all study drugs CFTRinh-172 reported in S3.
PFS in all randomised patients
PFS in patients with PTEN-low tumoursb
OS in all randomised patients
OS in patients with PTEN-low tumoursb
CI, confidence interval; CR, complete response; HR, hazard ratio; mFOLFOX6, modified regimen of leucovorin, 5-fluorouracil and oxaliplatin; NE, not evaluated; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; PTEN, phosphatase and tensin homolog; SD, stable disease. a Unstratified analysis; HR of ipatasertib/mFOLFOX6 versus placebo/mFOLFOX6.
b PTEN-low defined as no cytoplasmic PTEN expression (IHC Z 0) in 10% of tumour cells; n Z 15 for ipatasertib/mFOLFOX6 and n Z 21 for placebo/mFOLFOX6.
c By log-rank test.
rate, 35.4%) versus the ipatasertib arm (12.1 months; 90% CI, 10.3e14.6; event rate, 54.9%; HR, 1.85; 90% CI, 1.23e2.79) (Table 2). A similar OS trend was observed in the PTEN-low subgroup though based on fewer events (Table 2). More patients in the placebo versus ipatasertib arm received post-progression thera-pies (64.6% versus 49.3%; S6). Objective responses (mostly partial responses) were observed in over half of the patients in both arms (Table 2). An additional 28e30% of patients in both arms had stable disease as the best response. No further analyses of tumour response in patients with PI3K/Akt pathwayeactivated tumours were performed. Maximum changes in tumour size from baseline are shown in S7. One patient who had a complete response had an activating muta-tion in AKT1 (E17K mutation) in a tumour biopsy sample in her gastric cancer performed locally by the investigator. This patient was a 73-year-old women with stage IV gastric cancer of the intestinal type, with me-tastases to the peritoneum; she continued single-agent ipatasertib for 36 months and remained progression free during this time.
The percentages of patients with 1 AE (all grade), grade 3 AEs and AEs leading to interruption of
ipatasertib/placebo were similar between arms (Table 3). Patients receiving ipatasertib had a greater number of AEs leading to treatment withdrawal and dose reduc-tion (Table 3).