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

• Published in: The Lancet (British edition) 2008-07, Vol.372 (9633), p.145-154
• Main Authors: Wood, Christopher, MD, Srivastava, Pramod, MD, Bukowski, Ronald, MD, Lacombe, Louis, MD, Gorelov, Andrei I, MD, Gorelov, Sergei, MD, Mulders, Peter, MD, Zielinski, Henryk, MD, Hoos, Axel, MD, Teofilovici, Florentina, MD, Isakov, Leah, MS, Flanigan, Robert, MD, Figlin, Robert, MD, Gupta, Renu, MD, Escudier, Bernard, MD
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Cancer Vaccines - adverse effects; Cancer Vaccines - therapeutic use; Cancer Vaccines/adverse effects/therapeutic use; Clinical medicine; Committees; Disease-Free Survival; Drug use; Female; Heat-Shock Proteins - adverse effects; Heat-Shock Proteins - therapeutic use; Heat-Shock Proteins/adverse effects/therapeutic use; Humans; Injection; Internal Medicine; Kidney Neoplasms - pathology; Kidney Neoplasms - prevention & control; Kidney Neoplasms - surgery; Kidney Neoplasms/pathology/prevention & control/surgery; Male; Middle Aged; Neoplasm Recurrence, Local - prevention & control; Observation; Patients; Postoperative Period; Risk Factors; Substance abuse treatment; Survival; Vaccines
• ISSN: 0140-6736; 1474-547X; 1474-547X
• DOI: 10.1016/S0140-6736(08)60697-2

Summary Background Treatment of localised renal cell carcinoma consists of partial or radical nephrectomy. A substantial proportion of patients are at risk for recurrence because no effective adjuvant therapy exists. We investigated the use of an autologous, tumour-derived heat-shock protein (glycoprotein 96)–peptide complex (HSPPC-96; vitespen) as adjuvant treatment in patients at high risk of recurrence after resection of locally advanced renal cell carcinoma. Methods In this open-label trial, patients were randomly assigned to receive either vitespen (n=409) or observation alone (n=409) after nephrectomy. Randomisation was done in a one to one ratio by a computer-generated pseudo-random number generator, with a block size of four, and was stratified by performance score, lymph node status, and nuclear grade. Vitespen was given intradermally once a week for 4 weeks, then every 2 weeks until vaccine depletion. The primary endpoint was recurrence-free survival. The final analysis of recurrence-free survival was planned to take place after 214 or more events of disease recurrence or deaths before recurrence had occurred. Analysis was by intention to treat (ITT). This study is registered with ClinicalTrials.gov , number NCT00033904. Findings 48 patients in the vitespen group and 42 in the observation group were excluded from the ITT population because they did not meet post-surgery inclusion criteria; the ITT population thus consisted of 361 patients in the vitespen group and 367 in the observation group. Final analysis of recurrence-free survival was triggered in November, 2005. Re-review of all patients in the ITT population by the clinical events committee identified 149 actual recurrences (73 in the vitespen group and 76 in the observation group), nine deaths before recurrence (two in the vitespen group and seven in the observation group), and 124 patients with baseline metastatic or residual disease (61 in the vitespen group and 63 in the observation group). Thus, after a median follow-up of 1·9 years (IQR 0·9–2·5) in the ITT population, recurrence events were reported in 136 (37·7%) patients in the vitespen group and 146 (39·8%) in the observation group (hazard ratio 0·923, 95% CI 0·729–1·169; p=0·506). After continued follow-up until March, 2007, there had been 70 deaths in the vitespen group and 72 in the observation group (p=0·896); however, overall survival data were not mature, and patients continue to be followed up for survival. In predefined ex