"Ovarian cancer pill 'effective' at treating men with prostate cancer," The Independent reports after a small trial found the drug olaparib slowed tumour growth in men with a certain type of prostate cancer.
The trial involved 50 men with advanced prostate cancer who had not responded to other treatments. All of them were given olaparib. By the end of the study follow-up, 35 (70%) had died. Men who had a type of genetic mutation affecting DNA repair lived longer than those who did not.
It is hoped the drug could serve as a targeted treatment for this sub-type of prostate cancer in the same way Herceptin is used for breast cancer associated with the HER2 protein.
But one practical drawback of using olaparib in this way is the cost. It's reported a course of the drug costs £4,740 a month.
Olaparib is licensed for treatment of ovarian cancer, although the National Institute for Health and Care Excellence (NICE) has not approved it for NHS funding because of concerns about cost effectiveness.
Importantly, the study did not have a comparison group, so we don't know how long the men would have lived for if they had been given another treatment or no treatment at all. Research of this kind will probably be required before NICE makes a judgment about the use of olaparib for prostate cancer.
Where did the story come from?
The study was carried out by researchers from many different institutions: the Institute of Cancer Research, Royal Marsden NHS Foundation Trust, University College London Hospital, Queens University Belfast, the University of Leeds, Churchill Hospital, the University of Liverpool, Beatson West of Scotland Cancer Centre, and The Christie Hospital in the UK, and the University of Michigan, Weill Cornell Medical College, and Thomas Jefferson University in the US.
It was funded by grants from Cancer Research UK, Stand Up to Cancer-Prostate Cancer Foundation, Prostate Cancer UK, the Medical Research Council, the National Institute for Health Research, Swiss Cancer League and AstraZeneca, the manufacturer of olaparib.
Many of the researchers said they had conflicts of interest, including research grants, payments and other support from a number of pharmaceutical companies, including AstraZeneca in some cases. Two researchers also had payments related to patents for this drug class.
These potential conflicts of interest are to be expected when researchers study the effects of new drugs, as this type of research is largely industry funded.
The study met with possibly misguided enthusiasm in the media. The Mail Online's headline said the drug "can halt prostate cancer growth" without making it clear the effect lasted only a matter of months. Several news sources reported on the "row" over funding for the drug, which is not currently approved for NHS use.
What kind of research was this?
This was an open-label, single group study, where all the patients were given the same treatment. This means we cannot tell whether their results would have been different if they had been given different treatments or no treatment at all. It is a phase two trial.
Drugs usually need to show positive results from phase three trials, which are usually bigger and more rigorous, before they are licensed to be used for a particular disease.
What did the research involve?
The researchers recruited a group of men with prostate cancer that had not responded to previous treatment whose cancer had spread to their bones (metastatic prostate cancer). They treated them all with the drug olaparib and followed them up to see what happened.
At the start of the trial, the men had biopsy samples of their tumours taken, which were analysed for defects in the way the genes repaired DNA. The researchers thought the men with these defects were likely to respond to the treatment better than those without – the treatment is thought to act on DNA repair defects in other cancers.
They tested the men to see whether they responded to treatment in one of three main ways: shrinking tumours, a lower concentration of cancer cells in their blood, and lower levels of prostate specific antigen (PSA), a chemical produced by prostate cancer tumours.
They also looked at how long the men lived after starting treatment, and how long before they showed signs of the disease getting worse.
The researchers then compared results between the men with and without DNA repair defects.
What were the basic results?
The researchers said 16 of the 49 patients they could evaluate (33%, 95% confidence interval, 20 to 48) responded to olaparib, measured by either PSA levels, tumour cells in the blood or shrinking tumours, although they later said one of those men "had little evidence of a true response".
They said 14 of the men who responded had clear signs of DNA repair genetic mutations. Of the 16 men with genetic mutations of this type, 14 responded to olaparib, giving a much higher response rate of 88%.
The men with DNA mutations lived 13.8 months on average, compared with 7.5 months for the other men. It also took more time for their cancers to progress.
The most common side effects were anaemia (affecting 20%) and fatigue (affecting 12%). Some men had to take a reduced dose or discontinue the medication because of the side effects.
How did the researchers interpret the results?
The researchers said their results show men with specific DNA repair mutations in their tumours respond to olaparib, and this group accounts for about 25% to 30% of men with prostate cancer that has not responded to other treatment. They said testing men's tumours for these mutations before they start treatment is "feasible".
The researchers said the evidence of the effectiveness of olaparib in this group of men comes from increased time to tumour progression, shrinkage of tumours, and drops in PSA and cancer cells in the blood. However, they did say that, "We cannot yet determine whether olaparib improves overall survival" in this group of men.
Prostate cancer is common in the UK, so news of new treatment options is always welcome. However, this study does not show for certain that olaparib works better than no treatment, even for men with the DNA repair mutations identified in the study as responding to treatment.
The first problem is the lack of a comparison group. We can see what happened to the men who took the drug, but not what might have happened if they had not taken it, or if they'd taken another type of treatment not already tried.
And most of the men treated did not get any benefit from the drug. Only 16 of the 49 men assessed showed any signs of responding to treatment.
For the 16 men who had DNA repair mutations, the results were more impressive, which suggests future trials of olaparib should be focused on men who come into this category. Comparing the two groups, they lived six months longer on average than those without DNA repair mutations.
While the results for the 16 men who had the mutations were interesting, 16 men is a small group to rely on. We need to see bigger studies of men with these types of mutations to confirm whether they all respond as well as the men in the study.
For men with prostate cancer, there are reasons to be cautious about the possibility of being treated with olaparib.
Genetic profiling of tumour biopsies to look for mutations is not routine, so they may not know whether they are likely to fall into the group that may benefit from the drug. The drug has not been licensed for prostate cancer yet, and we don't know how long that might take.
And there is also the issue of cost. Several funding bodies have rejected its use on the NHS for ovarian cancer. We don't know whether it would be accepted as cost effective for prostate cancer based on the evidence in this study.
Overall, this is exciting research that shows how treatments might be targeted at the level of specific genetic mutations in the future.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
The Independent, 28 October 2015
BBC News, 29 October 2015
Mail Online, 29 October 2015
Daily Mirror, 29 October 2015
Links to the science
The New England Journal of Medicine. Published online October 29 2015