Efficacy of Nexavar, Treatment of Patients With Advanced Renal Cell Carcinoma (RCC)*

Nexavar — significantly doubled progression-free survival (PFS) — 24 wks vs 12 weeks^1,^2*

Nexavar achieved a 56% reduction in risk of progression vs placebo

^aHazard ratio (HR) defines the relative likelihood of experiencing a particular event. For example, an HR of 0.5 indicates one half the risk compared to the control. HR is from Cox regression model with the following covariates: MSKCC (Memorial Sloan-Kettering Cancer Center) prognostic risk category (also known as Motzer criteria) and country. P value is from 2-sided log-rank test stratified by MSKCC prognostic risk category and country.

Trial design: phase III, international, multicentre, randomised, double-blind, placebo-controlled trial in patients with advanced RCC who had received one prior systemic therapy.

Adapted from Escudier et al.

The effect of Nexavar on PFS was consistently demonstrated regardless of age, prognostic category, prior cytokine therapy, presence of lung or liver metastases, time since diagnosis²
Doubling of median PFS was consistent in patients with no prior cytokine therapy⁷: 25 weeks with Nexavar vs 12 weeks with placebo

All patient subsets experienced PFS benefit

Based on the statistical significance and magnitude of the PFS benefit, patients were un-blinded and placebo patients allowed to crossover to Nexavar in May 2005²
Tumour response was determined by independent radiological review according to RECIST criteria. Of the 335 patients who were evaluable for response, 80% of Nexavar patients experienced clinical benefit (CR+PR+SD)²
The gain in PFS in Nexavar-treated patients primarily reflects the stable disease population²

TARGET Study Timeline

Statistically significant increase in PFS led to crossover of placebo patients to Nexavar therapy^2,^3*

TARGET key study timeline points

Nexavar significantly increased PFS vs placebo (P<.000001), leading to protocol amendment to allow for crossover of placebo patients to Nexavar therapy²
- 48% (216/452) of placebo patients were crossed over to Nexavar in May 2005, making it highly likely that OS results would be confounded³

^bITT = intent-to-treat.

^cBased on data from June 2005 crossover.

Nexavar — preplanned placebo-censored analysis demonstrated significant OS advantage^3*

Preplanned placebo-censored analysis censoring data for placebo patients who crossed over to Nexavar therapy.

TARGET preplanned placebo-censored OS analysis

^dNexavar therapy demonstrated a significant survival advantage in a preplanned placebo-censored analysis censoring placebo at crossover (HR: 0.78; 95% CI, 0.62-0.97; P=.0287) O'Brien-Fleming threshold for statistical significance a=.037.

Final Median OS³

17.8 months with Nexavar (n=451) vs 15.2 months with placebo (n=452)
(HR: 0.88; 95% CI, 0.74-1.04; P=.146)
– Final OS results were confounded due to crossover
– 48% (216/452) of placebo patients crossed over to Nexavar

*Nexavar is indicated for the treatment of patients with advanced renal cell carcinoma who have failed prior interferon-alpha- or interleukin-2-based therapy or are considered unsuitable for such therapy.

Next: Safety Profile

Term

Explanation for term.