ASCO - Cancer vaccines given boost but much work remains

This year’s Asco contained much positive news about cancer vaccines, injecting a well needed boost of confidence into a space that suffered a number of high profile set backs last year.

The field is certainly diverse, ranging from complex personalised approaches like Accentia Biopharmaceuticals’ BiovaxID which received a huge amount of attention after being chosen for presentation at the conference’s plenary session, to more straightforward techniques like Merck KGaA’s Stimuvax, which reported highly encouraging phase II results. Despite this progress cancer vaccines are still far from reaching their potential, and researchers at the conferences stressed that further work must be done on boosting effectiveness, and said finding subsets of patients who will benefit the most must be a focus.

Could do better

A melanoma vaccine developed by the National Cancer Institute provides a good example of the first of these issues. Phase III results with the shot, called gp100 and which has no commercial backers, were presented, showing a significant improvement in progression free survival and clinical responses, and a trend for overall survival.

The vaccine is comprised of simple peptides and is cheap and simple to make, the investigators said. It primes lymphocytes, or T-cells, to recognise the tumour cells, and in the trial was administered along with interleukin-2, an immunostimulant made by Novartis which induces T-cell proliferation.

In effect, the vaccine trains an army to attack the tumour. Dr Patrick Hwu, of the MD Anderson Cancer Center who was involved in the trial, says the focus now is on getting an even better response to the vaccine.

“We can do better,” he told journalists. “There are lots of agents we can combine with.” Another trial will be run to try to replicate the results, possibly using anti-CTLa-4 as well as IL-2, which would effectively “take the brakes off the immune system”, he says.

Trials of vaccines in combination with biological agents or stem cell therapies are also avenues to explore.

Pick your battle

The need to boost responses is highlighted by the fact that many trials of cancer vaccines end up concluding that those with less severe illnesses respond much better. Just like another headline grabber at Asco Antigenics found with its kidney cancer Oncophage; a subset analysis revealed that those patients at a lower risk of disease recurrence responded much better.

This not only highlights the need to boost effectiveness. It illustrates how important it is for companies to conduct small studies to identify the ideal patient population before starting expensive phase III trials. Considering many of the companies working in this field are small and cash-constrained, like Antigenics, avoiding costly and ultimately disappointing phase III trials is incredibly important.

This approach has given Merck KGaA the confidence to progress its vaccine, Stimuvax, into phase III trials. Long-term safety data from a phase II trial conducted in inoperable advanced non-small cell lung cancer (NSCLC) announced at the conference were encouraging, and revealed that eight patients are still alive, more than eight years after first receiving treatment. Median survival for this population is usually between 9 and 13 months.

Stimuvax is again a very simple vaccine, and works by alerting the immune system to an antigen found on tumours called MUC1. A phase IIb trial found a markedly stronger response in patients with locally or less advanced tumours, and this population has been selected for the phase III trial, which should yield results in 2011.

“The time is over when you offer a drug to all cancer patients, or tumours of all stages,” Dr Wolfgang Wein, Merck KGaA’s vice president of oncology, told EP Vantage. “We have to look much more carefully at what is the tumour type, what is the type of immune system, what stage do we have, what is the situation of the patients, and so forth. I think therapies will be much more tailored (in the future) and increasingly personalised so everybody is well advised to look very carefully at these prognostic factors” when designing trials.

Of course, this sentiment is true for all cancer treatments, not just vaccines. But if the many smaller companies going it alone in this field want to conserve their cash, it is certainly one to bear in mind.

Proof of principle

Meanwhile, the results for lymphoma vaccine BiovaxID, despite being honoured with a spot at Asco’s plenary session, left many questions unanswered. An official review of the data was delivered by Dr Ronald Levy of Stanford Medical School, who is credited with developing a concept of harnessing antibodies to fight cancer that led to the creation of the first approved antibody-based immunotherapy, Rituxan.

He concluded that the BiovaxID data only established a proof of principle and that further evidence was needed. One major draw back is that Rituxan is now widely used to treat lymphoma, meaning that studies in combination or following treatment with the Biogen Idec drug need to be conducted.

The manufacturing technique was also questioned, in terms of its practicality. Although it improved over the seven years it took to conduct the trial, it still took three months to engineer the vaccine by the end of the study in 2007.

Far from guaranteed

BiovaxID is created following a biopsy to gather a patient’s individual tumour cells, a technique employed by Dendreon with prostrate cancer vaccine Provenge. After a tumultuous development path Provenge will be assessed by regulators later this year; meanwhile Antigentics is waiting on a decision from European regulators for Oncophage.

Success in front of regulators for these two candidates, arguably the two most advanced, novel cancer vaccines, is far from guaranteed. It is interesting to note that big pharma still remains largely on the sidelines in the field, being so far reluctant to commit money to this high risk field. However the step up in positive news from the developers of these drugs is encouraging, and if progress continues it could mean that changes in the near future.

“In general we all know the field has been difficult in the last decades,” Dr Wein says. “But today the scientific community is a lot more encouraged and expects a lot more from cancer vaccines.”

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