Vaccine yet to prove itself for renal cell carcinoma with residual disease

Tumour-derived drug vitespen (oncophage) has shown no advantage in recurrence-free survival, for patients who have undergone nephrectomy for renal cell carcinoma.

The study, published in the Lancet July 3^rd, was the largest to date, showed a turn from oncophage’s seemingly promising performance in early trials, to disappointment approaching phase III.

An exploratory analysis of early-stage kidney cancer patients (stage I or II disease) had previously signalled a possible reduction in recurrence with the vaccine (15.2% versus 27%, hazard ratio 0.576, P=0.056), which researchers had said would require further validation.

The combined rate of recurrence and death in this follow-up phase III trial was similar through almost two years of follow-up in nephrectomy patients given the vaccine as adjuvant therapy compared with observation (37.7% versus 39.8%, P=0.506).

After an additional 17 months of follow-up in the randomised phase III trial, survival still showed no improvement with the vaccine against peptide-bound heat-shock protein purified from patients' tumours (P=0.896).

Patients were randomised to observation after surgery or treatment with oncophage intended to start within eight weeks of surgery.

The vaccine was given at a dose of 25 µg intradermally once a week for four weeks, then every two weeks until vaccine supply depletion or disease progression for a total of 12 injections on average.

A total of 124 patients had remaining disease at baseline after surgery rendering them ineligible for the trial. And of these, 92 were reported to have disease recurrence whereas they actually had disease progression.

Speaking to ‘Medscape Oncology’, lead study author Christopher Wood, MD, from the MD Anderson Cancer Center in Houston, Texas, put the poor results down to the difficulties of adjuvant trials in an evolving field:
"Vaccine therapies continue to hold promise. The problem is these studies are difficult to conduct and are a lot of work. You need huge numbers, and the time to recurrence is long."

The researchers added that their finding of a non-statistically significant reduction in recurrence events among patients with stage I or II kidney cancer with oncophage, while in a pre-specified analysis, could have been a result of statistical noise resulting from the small sample size of patients with more advanced cancer.

"The observation that treatment with vitespen [oncophage] confers an apparent clinical benefit to patients with earlier stage disease with better prognosis is biologically plausible," they said:  “Later-stage tumours have more mechanisms to resist immunotherapy. Additional research is thus warranted to further explore the use of vitespen in patients with early stage renal cell carcinoma."

In April 2008, oncophage became the first cancer vaccine to be approved in a major pharmaceutical market. The Russian Ministry of Public Health issued a registration certificate for its use as an adjuvant treatment for renal cell carcinoma for patients at intermediate-risk of disease recurrence. Presently, there are no approved products anywhere in the world for this stage of renal cell carcinoma patients.

By the end of 2008 Antigenics aims to file for conditional authorisation in Europe for oncophage as an adjuvant treatment for kidney cancer patients. Several discussions and meetings were held with the European Medicines Agency (EMEA) during the first half of 2008, including meetings with authorities from the lead countries that have been assigned the responsibility for reviewing the oncophage marketing authorisation application.


Original article: 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