For many years, the measure of the effectiveness of a new cancer drug was “overall survival” — how long patients survived after being treated with the drug.
More recently, however, cancer drugs are often approved by government regulators based on a measure known as “progression-free survival” — the length of time patients can expect to live with the disease without it getting worse.
Researchers and drug companies tend to prefer progression-free survival because it makes the studies shorter and less expensive, enabling new drugs to make it through the approval process faster.
Progression-free survival is not the same as overall survival, however. Indeed, research has uncovered evidence that progression-free survival leads to a better overall survival benefit in only limited situations.
And that may not be the only problem with relying on progression-free survival as a marker for a cancer drug’s benefits. According to a new study, published online this week in JAMA Internal Medicine, there is no evidence in the medical literature of a significant link between progression-free survival and quality of life.
“Given the increased use of progression-free survival as the primary outcome in new oncology drug trials, and uncertainty of overall survival, it remains possible that patients are receiving toxic and/or expensive treatments without experiencing important benefits,” said Feng Xie, the study’s senior author and a health economist at McMaster University in Ontario, Canada, in a released statement.
For the study, Xie and his colleagues searched the medical literature between January 2000 and May 2016 for randomized clinical trials (in any language) that used both progression-free survival and health-related quality of life as endpoints. They found 38 such studies, which included a total of almost 14,000 cancer patients, aged 18 to 93, with 12 different types of cancer.
The researchers then pooled and analyzed the data from those studies. The analysis revealed no significant association between progression-free survival and the patients’ physical and emotional quality of life.
Comparing the data from the studies was a challenge, in large part because the studies defined and measured quality of life in different ways. Only 13 of the 38 studies included emotional quality of life in their assessments, for example.
Also problematic was the finding that 24 of the studies followed the patients’ quality of life for a shorter period of time than they followed progression-free survival.
The study comes with several caveats, as Xie and his colleagues point out in their paper. The failure of many of the studies to track quality of life for as long as they measured progression-free survival may have resulted in some of the studies not capturing later quality-of-life benefits, for example. In addition, the relatively small number of randomized trials eligible for this study may have statistically skewed the results.
The researchers believe, however, that the methods they used for their analysis outweigh these limitations.
“[Progression-free survival] advocates believe that [progression-free survival] indicates disease control and stabilization, leading to reduction in disease symptoms, thus implying clinical benefit through improvement in [quality of life],” they write.
“Our results cast doubts on such assumptions,” they add.
Needed: more rigorous measures
Future research involving cancer drugs should focus on overall survival and/or include “rigorous and trustworthy” measures of quality of life as an endpoint, Xie and his colleagues conclude.
“Access to these types of drugs is costing our healthcare system a lot of money, and the troubling fact is that we do not have strong enough evidence to show that some of these drugs can extend a patient’s life or improve their quality of life,” said Xie.
“Therefore, to ensure patients are truly obtaining important benefit from cancer therapies, clinical trial investigators should measure health-related quality of life directly and accurately, ensuring adequate duration and follow-up, and publish it,” he added.
FMI: You’ll find an abstract of the study on the JAMA Internal Medicine website, although the full study is behind a paywall.