The evidence supporting this regimen comes from a three-arm multicenter, randomised phase III trial, reported by Hudes et alr
Between July 2003 to April 2005, 626 patients at high risk of relapse, were enrolled in the study. 209 were randomised to receive 25 mg of IV temsirolimus weekly, 207 to receive 3 million units of interferon alfa ( increasing to 18 million units ) subcutaneously three times a week, and 210 to receive a combination of 15 mg of temsirolimus weekly plus 6 million units of interferon alfa three times a week.
The primary end point was overall survival. Secondary end points were progression free survival, objective response rate and the clinical benefit rate.
The INTORSECT trial demonstrated no statistically significant progression free survival advantage for temsirolimus compared with sorafenib (4.3 vs 3.9 months repsecitvely P=0.19) or overall response rate following first line sunitinib. The difference in overall survival was significant in favour of sorafenib (stratified HR 1.31; 95% CI 1.05 to 1.63; two sided P=0.01). Median overall survival in the temsirolimus and sorafenib arms was 12.3 and 16.6 months respectively.r
Further to this the INTORACT trial demonstrated that temsirolimus/bevacizumab combination was not superior to interferon/bevacizumab for first line treatment in clear-cell metastatic renal cell carcinoma.r
Efficacy
Patients who received temsirolimus alone had longer overall survival (hazard ratio for death, 0.73; p=0.008) and progression free survival (p<0.001) than patients who received interferon alone.
Overall, the combination group did not differ significantly from that in the interferon group (hazard ratio, 0.96; p=0.70)
Hudesr |
Temsirolimus alone
(n=209) |
Interferon alfa alone
(n=207) |
Temsirolimus plus interferon alfa
(n=210) |
Overall survival |
10.9 months |
7.3 months |
8.4 months |
Progression free survival* |
3.8 months |
1.9 months |
3.7 months |
Objective response rate |
8.6% |
4.8% |
8.1% |
Clinical benefit rate** |
32.1% |
15.5% |
28.1% |
* PFS as determined by the site investigators
**Objective response or stable disease for > 24 weeks
Kaplan-Meier Estimates of Overall Survival and Progression-free Survivalr
© New England Journal of Medicine 2007
Toxicity
Rash, peripheral oedema, hyperglycaemia and hyperlipidaemia were more common in the patients receiving temsirolimus, whereas asthenia was more common in the groups receiving interferon. There were fewer patients with grade 3 or 4 adverse events in the temsirolimus group (67%) than in the interferon group (78%)(p=0.02).
23% and 66% of the patients in the temsirolimus group required a dose reduction and dose delay respectivelyr
© New England Journal of Medicine 2007