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Torisel versus Interferon, Subset Analysis
Correlation of Survival: Torisel versus Interferon-alpha
Janice Dutcher of Our Lady of Mercy Hospital in the Bronx presented a poster examining the correlation of survival with tumor histology, age, and prognostic risk group for patients with advanced kidney cancer receiving Torisel (temsirolimus) or Interferon-alpha. Data were analyzed from the Phase 3 Global Advanced Renal Cell Carcinoma Trial (ARCC) reported on by the primary investigator Gary Hudes at ASCO 2006 (we reported on Dr. Hudes' study last year, see Report from ASCO 2006 or NEJM 2007;356:2271-2281).
Torisel is an mTOR inhibitor, where mTOR is a protein involved in cell proliferation and survival. In this case, the objective is to inhibit tumor growth. Gary Hudes reported an increase in survival benefit for Torisel over Interferon-alpha in the ARCC trial, which led to FDA approval of the drug in May, 2007. The objective of this study is to stratify the results by histology, age, and prognostic risk group. This was a three-arm trial, Torisel, Interferon-alpha, and a combination of the two. For this analysis, the third arm was ignored.
Histology
|
Overall Survival and PFS by Tumor Histology |
||||
|
Histology Type |
INF (n = 207) |
Torisel (n = 209) |
||
|
n (%) |
Median, mos |
n (%)
|
Median, mos |
|
|
Overall Survival |
||||
|---|---|---|---|---|
| Clear cell |
170 (82.5) |
8.2 |
169 (82.0) |
10.6 |
|
Other |
36 (17.5) |
4.3 |
37 (18.0) |
11.6 |
|
Progression-free Survival, Independent Assessment |
||||
|
Clear cell |
170 (82.5) |
3.8 |
169 (82.0) |
5.5 |
|
Other |
36 (17.5) |
1.8 |
37 (18.0) |
7 |
Approximately two-thirds of the 18% "Other" pathology consisted of indeterminate pathology and one-third was non-clear cell, mostly papillary.
It is clear that Torisel benefits both clear cell and non-clear cell patients, including papillary. As Dr. Dutcher concluded in her paper, Torisel may be of greater benefit to patients with non-clear cell pathology than those with clear cell since cytokines such as Interferon-alpha and Interleukin-2 have not shown as much activity in non-clear cell patients.
Age
|
Overall Survival and PFS by Age |
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|
Age Group |
INF (n = 207) |
Torisel (n = 209) |
||
|
n (%) |
Median, mos |
n (%) |
Median, mos |
|
|
Overall Survival |
||||
|---|---|---|---|---|
|
<65 yrs |
142 (68.6) |
6.9 |
145 (69.4) |
12.0 |
|
≥65yrs |
65 (31.4) |
8.3 |
64 (30.6) |
8.6 |
|
Progression-free Survival, Independent Assessment | ||||
|
<65 yrs |
142 (68.6) |
3.1 |
145 (69.4) |
5.9 |
|
≥65yrs |
65 (31.4) |
3.5 |
64 (30.6) |
3.7 |
Torisel benefits patients under 65 years old, but as we see from the data there was no comparative benefit of Torisel over Interferon-alpha for patients over 65 years old.
Prognostic Risk Group
|
Overall Survival and PFS by by MSKCC Risk Group |
||||
|
MSKCC Prognostic |
INF (n = 207) |
Torisel (n = 209) |
||
|
Features |
n (%) |
Median, mos |
n (%) |
Median, mos |
|
Overall Survival |
||||
|---|---|---|---|---|
|
Intermediate |
51 (24.6) |
17.7 |
64 (30.6) |
13.0 |
|
Poor |
156 (75.4) |
6.0 |
145 (69.4) |
10.2 |
|
Progression-free Survival, Independent Assessment | ||||
|
Intermediate |
51 (24.6) |
5.6 |
64 (30.6) |
7.0 |
|
Poor |
156 (75.4) |
2.3 |
145 (69.4) |
5.1 |
Torisel showed a clear survival advantage over Interferon-alpha for poor risk patients, but for intermediate risk patients, Interferon-alpha patients had a longer survival albeit a shorter PFS (progression-free survival).
Below are listed only those serious adverse events that have occurred in over 10% of the population.
|
Percentage of Patients with Grade 3/4 Adverse Events (≥10%) by Age |
||||
|
Adverse Event |
Age < 65 yrs |
Age ≥ 65 yrs |
||
|
INF (n=137) |
Tems (n=145) |
INF (n=63) |
Tems (n=63) |
|
|
Any adverse event |
79 |
68 |
79 |
71 |
|---|---|---|---|---|
|
Asthenia |
23 |
10 |
33 |
14 |
|
Dyspnea |
6 |
8 |
6 |
10 |
|
Nausea |
3 |
3 |
10 |
2 |
|
Hematologic and Laboratory | ||||
|
Anemia |
24 |
20 |
16 |
19 |
|
Neutropenia |
7 |
3 |
10 |
2 |
|
Lymphopenia |
4 |
3 |
10 |
8 |
|
Hyperglycemia |
2 |
10 |
0 |
13 |
There is no difference in adverse events with respect to the above age categories, but overall, Torisel patients had fewer side effects than Interferon-alpha patients.
In conclusion, this study points to the benefit of Torisel in both the clear cell and the non-clear cell pathology population, especially papillary. We have so few studies for the latter population so these are welcome results. This study indicated that the age of the patient may be a factor in response to Torisel with the over 65 group having a lower survival rate. It will be interesting to see what future age-stratified trial results will show.