"Trial finds combination of pancreatic cancer drugs extends survival," The Guardian reports. The results of a trial that combined the use of two chemotherapy drugs has led to calls for this approach to become the…
"Trial finds combination of pancreatic cancer drugs extends survival," The Guardian reports.
The results of a trial that combined the use of two chemotherapy drugs has led to calls for this approach to become the new protocol for pancreatic cancer treatment.
The trial showed people lived an average of 2.5 months longer if they took two drugs than if they took just one. Pancreatic cancer has a poor outlook compared with many other cancers.
Using information from the study, researchers estimated that the chances of people living for five years were 28.8% for those who took both drugs, compared with 16.3% for those treated with one drug.
However, not everyone involved in the trial was followed up for five years, so we don't know how reliable these longer-term estimates are.
The researchers say the two-drug combination should be "the new standard of care" for people who've had surgery for pancreatic cancer.
But people who took both drugs were more likely to stop treatment early because of the toxic side effects of chemotherapy.
This is an important consideration for people whose treatment can only prolong life and not achieve a cure, as there is always going to be a trade-off between survival time and quality of life.
Where did the story come from?
The study was carried out by researchers from the universities of Liverpool and Manchester, the Royal Liverpool University Hospital, Clatterbridge Cancer Centre, Manchester Royal Infirmary, the Royal Marsden Hospital, Weston Park Hospital, the Royal Free Hospital, St James's University Hospital, Bristol Haematology and Oncology Centre, and the Royal Surrey County Hospital, all in the UK, as well as the Karolinska Institute and the University of Uppsala in Sweden, and the University of Hamburg in Germany.
It was funded by Cancer Research UK. Several of the study authors reported financial links with pharmaceutical companies.
The study was published in the peer-reviewed journal The Lancet on an open access basis, so it's free to read online.
The UK media reported the study enthusiastically, overstating the results in some cases.
The Daily Mirror reported that, "A drug combination which can help pancreatic cancer sufferers survive for at least five years has been hailed as a breakthrough", which is simply not true: less than a third of people taking the drug combination were expected to survive for five years.
Most, including The Guardian, The Independent and Mail Online, led their reports with the study's secondary outcome, the five-year survival data, without explaining this was an estimate, not a report of how long people actually lived.
The less impressive figure of an average 2.5 extra months of life was only reported in The Guardian.
What kind of research was this?
This was a randomised controlled trial (RCT), which is usually the best way to compare two types of treatment to see which works best.
Unlike most RCTs, both patients and doctors knew which treatment they were getting – the study was not blinded, which introduces the risk of bias. The reasons for this were not explained in the study.
What did the research involve?
Researchers recruited 732 people who'd had surgery for pancreatic cancer from 92 hospitals in the UK, Germany, France and Sweden, starting in 2008 and finishing in 2014.
They randomly assigned them to take either gemcitabine alone or gemcitabine plus capecitabine, another chemotherapy drug.
People were assigned to six cycles of the drugs, with one cycle taking around four weeks. The researchers reviewed patients every three months for up to five years.
The study's primary outcome measure was overall survival time in both groups from entry into the trial.
Researchers estimated how many patients would have survived two years and five years after entry into the trial, and looked at rates of cancer relapse.
They also looked at toxicity from the cancer drugs, and compared how many people in each group had adverse events, such as diarrhoea or fever, and how many stopped treatment early.
The study was stopped and the results reported early on the request of the safety committee, which had carried out interim analyses of the results.
They said after 400 deaths were reported, it was clear that the combination therapy was more effective than the single drug.
What were the basic results?
People who took both chemotherapy drugs were likely to live longer:
- average survival for people taking gemcitabine was 25.5 months (95% confidence interval [CI] 22.7 to 27.9)
- average survival for people taking gemcitabine plus capecitabine was 28 months (95% CI 23.5 to 31.5)
- 78% of people who took gemcitabine alone and 74% who took the two drugs together either had a recurrence of their cancer or died
- an estimated 16.3% (95% CI 10.2 to 23.7) of people who took gemcitabine alone were expected to live for five years, compared with an estimated 28.8% (95% CI 22.9 to 35.2) who took the two drugs together
People who took the combination of drugs were also likely to have more adverse events and side effects.
Of people who took gemcitabine alone, 35% stopped treatment early, 41% of whom stopped as a result of side effects of the chemotherapy.
Of those taking the drugs combination, 46% stopped treatment early, 47% of whom did so because of side effects.
There were 481 serious adverse events in the gemcitabine only group, reported by 54% of people. This compared with 608 serious adverse events in the combination group, reported by 63% of people.
There was no difference between the two groups in terms of quality of life as measured by repeat questionnaires (hazard ratio 0.10, 95% CI 0.29 to 0.09).
How did the researchers interpret the results?
The researchers say the study showed the combination of drugs "significantly increased overall survival" and this happened with "an acceptable level of toxicity".
They say the combination of drugs "is the new standard of care" for people with pancreatic cancer after surgery.
Pancreatic cancer is one of the toughest cancers to treat, with lower survival rates than many other cancers.
Surgery is usually the first treatment, where possible. Some people also have chemotherapy or radiotherapy.
Recent studies have looked into how different types of chemotherapy might help improve survival.
This study shows that a combination of two chemotherapy drugs may help people live longer than taking one drug alone after surgery.
But this doesn't mean everyone taking those drugs will survive at least five years, despite the media headlines.
The researchers estimate 28.8%, or just over a quarter, of people who have surgery and take these two drugs will survive for at least five years.
For people who don't live that long, the potential improvements in lifespan are much smaller. The average difference in survival time for those taking the drugs combination was 2.5 months.
The downside is an increased chance of side effects from the chemotherapy drugs, which are usually taken for about six months.
In these sorts of circumstances, people often have to make a tough choice about whether or not to pursue a treatment that may extend their life by only a few months, but could also worsen their quality of life.
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