Results a includes adjudication for discrepant assessments between investigator radiological review and central radiological review
Analysis N
AFINITOR
N=207 Placebo
N=203 Hazard Ratio (95%CI) p-value
410 Median progression-free survival (months) (95% CI)
Investigator radiological review 11.0
(8.4 to 13.9) 4.6
(3.1 to 5.4) 0.35
(0.27 to 0.45) <0.001
Central radiological review 13.7
(11.2 to 18.8) 5.7
(5.4 to 8.3) 0.38
(0.28 to 0.51) <0.001
Adjudicated radiological reviewa 11.4
(10.8 to 14.8) 5.4
(4.3 to 5.6) 0.34
(0.26 to 0.44) <0.001
Figure 2: Kaplan-Meier Investigator-Determined Progression-free Survival Curves
Investigator-determined response rate was low (4.8%) in the AFINITOR arm and there were no complete responses. The overall survival results are not yet mature and no statistically significant treatment-related difference in OS was noted [HR=1.05 (95% CI: 0.71 to 1.55)].
Lack of Efficacy in Locally Advanced or Metastatic Functional Carcinoid Tumors
The safety and effectiveness of AFINITOR in patients with locally advanced or metastatic functional carcinoid tumors have not been demonstrated. In a randomized (1:1), double-blind, multi-center trial in 429 patients with carcinoid tumors, AFINITOR plus depot octreotide (Sandostatin LAR®) was compared to placebo plus depot octreotide. After documented radiological progression, patients on the placebo arm could receive AFINITOR; of those randomized to placebo, 143 (67%) patients received open-label AFINITOR plus depot octreotide. The study did not meet its primary efficacy endpoint of a statistically significant improvement in PFS and the final analysis of OS favored the placebo plus depot octreotide arm.
14.3 Advanced Renal Cell Carcinoma
An international, multi-center, randomized, double-blind trial comparing AFINITOR 10 mg daily and placebo, both in conjunction with best supportive care, was conducted in patients with metastatic RCC whose disease had progressed despite prior treatment with sunitinib, sorafenib, or both sequentially. Prior therapy with bevacizumab, interleukin 2, or interferon-α was also permitted. Randomization was stratified according to prognostic score1 and prior anticancer therapy.
Progression-free survival (PFS), documented using Response eva luation Criteria in Solid Tumors (RECIST) was assessed via a blinded, independent, central radiologic review. After documented radiological progression, patients could be unblinded by the investigator: those randomized to placebo were then able to receive open-label AFINITOR 10 mg daily.
In total, 416 patients were randomized 2:1 to receive AFINITOR (n=277) or placebo (n=139). Demographics were well balanced between the 2 arms (median age 61 years; 77% male, 88% Caucasian, 74% received prior sunitinib or sorafenib, and 26% received both sequentially).
AFINITOR was superior to placebo for PFS (see Table 14 and Figure 3). The treatment effect was similar across prognostic scores and prior sorafenib and/or sunitinib. Final overall survival (OS) results yield a hazard ratio of 0.90 (95% CI: 0.71 to 1.14), with no statistically significant difference between the 2 treatment groups. Planned cross-over from placebo due to disease progression to open label AFINITOR occurred in 111 of the 139 patients (79.9%) and may have confounded the |
