Multicenter Phase III Trial to Compare Radical Nephrectomy Plus Adjuvant Autologous Tumor Cell-Lysate Vaccine Versus Radical Nephrectomy Without Adjuvant Treatment for Renal Cell Carcinoma Stages pT2-3bN0-3M0: a 3-year Analysis

Reviewer: Thomas Dilling, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 20, 2002

Presenter: C. Doehn
Presenter's Affiliation: University of Luebeck Medical School
Type of Session: Scientific

Background

According to SEER data, 50% of renal cell carcinomas (RCC) are localized in extent.
The five-year survival rate for localized tumors is 90%, but drops to 60% if disease is regional in extent and 10% if metastatic.
Standard therapy consists of a radical nephrectomy.
Additional agents for treatment of this tumor have proven disappointing. Agents attempted have included interferon, vaccine therapies, and various chemotherapy combinations. None have proven better than the control arms in their respective studies.
These investigators report their 3-year results utilizing a vaccine developed from autologous tumor cell lysate.

Materials and Methods

558 patients were evaluated from January, 1997 to September, 1998.
365 patients were deemed eligible and entered onto the study.
Median age of patients was 59 years. ECOG Performance status was 0-2 in all patients.
Patients were randomized to radical nephrectomy alone versus radical nephrectomy followed by vaccine.
199 patients were placed into the control arm; 166 received vaccine.
Median tumor size in both arms was 6 cm.
70% of tumors were stage T2, 30% were T3.
Vaccine was administered beginning 4 weeks post-nephrectomy, then every four weeks for 6 months.
Patients received no additional immune stimulation as part of the study.
Patients were received follow-up evaluation every 6 months thereafter.

Results

Progression-Free Survival at 3 years was 84.2% in the vaccine arm and 80.9% in the control arm.
Subset analysis data was also presented, breaking patients into categories by T-stage.
PFS for T2 patients: 90.4% (vaccine) and 85.3% (control).
PFS for T3 patients: 80.5% (vaccine) and 62.8% (control).

Author's Conclusions

The presenter stated an apparent trend toward improved PFS in the vaccine arm.
If statistical analysis bears this out, it will be the first vaccine trial to demonstrate efficacy in RCC.

Clinical/Scientific Implications

It must be stressed that no statistical analysis has yet been performed on the data. The presenter states that this will be done in approximately 6 months, at 4 years of follow-up.
Furthermore, the study was not adequately statistically powered to determine difference in survival in difference subgroups based upon T-stage, as was presented here.
Until appropriate analysis is done, one cannot definitively state that the vaccinated patients had better outcome. These data are, nonetheless, promising.
This is a disease for which oncologists have historically had little to offer patients. It will be interesting to see what the final analyses of this data demonstrates.

Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.