6% (95% CI: 9.8, 15.9) in the AFINITOR plus exemestane arm versus 1.7% (95% CI: 0.5, 4.2) in the placebo plus exemestane arm. There were 3 complete responses (0.6%) and 58 partial responses (12.0%) in the AFINITOR plus exemestane arm. There were no complete responses and 4 partial responses (1.7%) in the placebo plus exemestane arm.
After a median follow-up of 39.3 months, there was no statistically significant difference in OS between the AFINITOR plus exemestane arm and the placebo plus exemestane arm [HR 0.89 (95% CI 0.73, 1.10)].
Table 12: Progression-free Survival Results a Exemestane (25 mg/day)
b Hazard ratio is obtained from the stratified Cox proportional-hazards model by sensitivity to prior hormonal therapy and presence of visceral metastasis
c p-value is obtained from the one-sided log-rank test stratified by sensitivity to prior hormonal therapy and presence of visceral metastasis
d Objective response rate = proportion of patients with CR or PR
e not applicable
Analysis AFINITOR
+ exemestanea
N = 485 Placebo
+ exemestanea
N = 239 Hazard ratio P-value
Median progression-free survival (months, 95% CI)
Investigator radiological review 7.8
(6.9 to 8.5) 3.2
(2.8 to 4.1) 0.45b
(0.38 to 0.54) <0.0001c
Independent radiological review 11.0
(9.7 to 15.0) 4.1
(2.9 to 5.6) 0.38b
(0.3 to 0.5) <0.0001c
Best overall response (%, 95% CI)
Objective response rate (ORR)d 12.6%
(9.8 to 15.9) 1.7%
(0.5 to 4.2) n/ae
Figure 1: Kaplan-Meier Progression-free Survival Curves (Investigator Radiological Review)
14.2 Advanced Neuroendocrine Tumors
Locally Advanced or Metastatic Advanced Pancreatic Neuroendocrine Tumors (PNET)
A randomized, double-blind, multi-center trial of AFINITOR plus best supportive care (BSC) versus placebo plus BSC was conducted in patients with locally advanced or metastatic advanced pancreatic neuroendocrine tumors (PNET) and disease progression within the prior 12 months. Patients were stratified by prior cytotoxic chemotherapy (yes versus no) and by WHO performance status (0 versus 1 and 2). Treatment with somatostatin analogs was allowed as part of BSC. The primary endpoint for the trial was progression-free survival (PFS) eva luated by RECIST (Response eva luation Criteria in Solid Tumors). After documented radiological progression, patients could be unblinded by the investigator; those randomized to placebo were then able to receive open-label AFINITOR. Other endpoints included safety, objective response rate [ORR (complete response (CR) or partial response (PR)], response duration, and overall survival.
Patients were randomized 1:1 to receive either AFINITOR 10 mg/day (n=207) or placebo (n=203). Demographics were well balanced (median age 58 years, 55% male, 79% Caucasian). Cross-over from placebo to open-label AFINITOR occurred in 73% (148/203) of patients.
The trial demonstrated a statistically significant improvement in PFS (median 11.0 months versus 4.6 months), resulting in a 65% risk reduction in investigator-determined PFS (HR 0.35; 95%CI: 0.27 to 0.45; p<0.001) (see Table 13 and Figure 2). PFS improvement was observed across all patient subgroups, irrespective of prior somatostatin analog use. The PFS results by investigator radiological review, central radiological review and adjudicated radiological review are shown below in Table 13.
Table 13: Progression-free Survival |
