UroToday.com – There currently exists a significant unmet medical need for a safe and effective adjuvant therapy that delays or prevents recurrence of renal cell carcinoma (RCC). Two studies using vaccine products as adjuvant treatment after nephrectomy have been completed with promising results.

A phase-III study compared adjuvant treatment with an autologous renal tumour cell vaccine (Reniale®) after radical nephrectomy versus radical nephrectomy alone in non-metastatic RCC (pT2-3b pN0-3, M0). Prior to surgery, 558 patients at 55 institutions in Germany were enrolled in the trial and were randomised to receive six intradermal vaccinations at 4-week intervals (Reniale® group), or no adjuvant therapy (control group). The primary endpoint of the trial was to reduce the risk of tumour progression. Overall survival (OS) and quality of life were secondary endpoints. The intention-to-treat (ITT) population consisted of 379 patients in the primary analysis. In total 177 patients in the Reniale® group and 202 patients in the control group were analysed. The 5-year progression-free survival (PFS) for patients at all tumour stages was higher for the vaccine group (77.4%) than for the control group (67.8%) (P = 0.0204).

Interestingly, patients with a higher risk (T3 subgroup) had higher benefit from an adjuvant treatment with Reniale® with a 5-year PFS of 67.5% in the vaccine group and 49.7% in the control group [1]. Updated results include a secondary ITT analysis (n=477) and OS data. The latter report shows a statistically significant benefit in favour of the vaccine for PFS (P=0.0476) and a favourable but not significant OS trend (P=0.1185). A per-protocol analysis (n=352) revealed a statistically significant PFS and OS in favour of the vaccine (P=0.024 and P=0.0356). The Reniale® vaccine was well tolerated with no serious vaccine-related adverse events [2].

A recent phase III study compared adjuvant vaccination with a heat-shock-protein-peptide complex (HSPPC-96; vitespen; Oncophage®) (n=361) with observation (n=367) in RCC patients at high risk of recurrence after nephrectomy. This study represents the largest study completed to date in the adjuvant RCC patient population and had the contribution of 118 clinical centres in 15 countries in North America and Europe. The study enrolled 818 patients who were randomised to receive vitespen (n=409) or no therapy (n=409) after nephrectomy. Vitespen was administered intradermally once a week for 4 weeks, then every 2 weeks until vaccine depletion. Analysis was completed in 361 patients in the vitespen group and 367 patients in the observation group.

After a median follow-up of 1.9 years in the ITT population, recurrence events were reported in 136 (37.7%) patients in the vaccine group and 146 (39.8%) in the observation group (hazard ratio: 0.923; 95% confidence interval (CI): 0.729-1.169; P=0.506). Thus, patients with RCC who received vitespen after nephrectomy showed no increased recurrence-free survival. Exploratory subset analyses showed fewer recurrences with vitespen in patients with earlier stage disease (American Joint Committee on Cancer stage 1 and 2). However, the difference between groups was not statistically significant. Recurrence events in patients with AJCC stage 1 and 2 were reported in 19 (15.2%) patients in the vitespen group and 31 (27.0%) in the observation group (hazard ratio 0.576; 95% CI: 0.324-1.023, P=0.056). A possible improvement in recurrence-free survival in patients with early-stage disease who received vitespen will require further validation. One serious adverse event – autoimmune thyroiditis of grade 2 severity – was observed in the vitespen group and was judged to be probably related to vitespen. No treatment-related grade 3 or 4 adverse events were reported [3].

Both RCC vaccines are important potential adjuvant treatments in selected patient groups with, as for virtually every cancer vaccine, no important toxicity. In contrast with less tolerated more toxic targeted agents that must be administered for extended periods of time, these RCC vaccines must only be given for a limited period. The urgent need for safe and effective adjuvant therapies for RCC should prompt investigators to further explore these vaccines. A possible area of research is the identification of other forms of immunostimulatory or targeted agents that when given in combination with the vaccine may optimize the vaccine effect.

References:
1. Jocham D, Richter A, Hoffmann L, et al. Adjuvant autologous renal tumour cell vaccine and risk of tumour progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomised controlled trial. Lancet. 2004 Feb 21;363(9409):594-9.
2. Doehn C. Prolongation of progression-free and overall survival following an adjuvant vaccination with Reniale in patients with non-metastatic renal cell carcinoma:Secondary analysis of a multicenter phase-III trial. 2006 [cited]
3. Wood C, Srivastava P, Bukowski R, et al. An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial. Lancet. 2008 Jul 12;372(9633):145-54.

Written by Hein Van Poppel, Steven Joniau and Stefaan W. Van Gool as part of Beyond the Abstract on UroToday.com

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