Progression-free survival (PFS) is now the dominant endpoint in cancer clinical trials, but simply prolonging time to progression without extending overall survival or quality of life does not justify additional therapy for many patients, new research indicates.
“The results of our study demonstrate that more than half of patients with advanced cancer would not want a treatment that delays time to progression on imaging without any improvement in survival or quality of life,” Christopher Booth, MD, an oncologist and professor at Queen’s University, Kingston, Ont., said in an interview.
Even with an overall survival benefit of 6 months, one in five patients said they would decline additional treatment, which indicates the limited value of extra months of life with better quality of life.
“This has very important implications for our field – how we design trials, how we write guidelines, and how we make treatment recommendations to our patients,” said Booth.
The findings highlight the importance of “making sure that we incorporate patient perspectives into what we do and the research around it,” agreed Richard Lee, MD, with City of Hope Comprehensive Cancer Center, Duarte, Calif., who wasn’t involved in the study.
“It’s easy for us to pick outcome measures that are important to us as researchers but really have very little value to the patient,” said Dr. Lee, associate editor (palliative care) for Cancer.Net, the American Society of Clinical Oncology patient information website.
The study was published online in the Journal of the National Cancer Institute.
It’s also unclear how much patients value additional time with no progression, especially if it means extra toxicity with no overall survival or quality of life gains.
In the current study, Dr. Booth and colleagues wanted to better understand patients’ attitudes toward a treatment that offers PFS but does not improve overall survival.
The study involved 100 patients who had received at least 3 months of systemic therapy for incurable solid tumors. Nearly two-thirds of the patients were older than 60. They were asked about their preferences and goals for additional therapy. A variety of primary cancer sites were represented, most commonly gastrointestinal, breast, lung, genitourinary, and brain.
Among the patients interviewed, 80 were currently receiving palliative systemic treatment. Only one patient described the intent as curative; 45% described it as intending to prolong life, and 5% described it as intending to improve quality of life. The remainder had a combination of goals.
Overall, patients expressed a variety of preferences about additional treatment.
More than half (52%) said they would decline additional treatment that only offered PFS gains, while 26% said they would accept more treatment in the absence of an overall survival benefit if it meant delaying disease progression by 3-9 months.
About one in six patients (17%) said they would prefer additional treatment, even without any gain in PFS. These patients expressed “wanting to fight or hoping that they would defy the survival statistics” – an attitude that is “not irrational,” the researchers noted, but rather reflects the “more must be better” line of thinking.
Compared with the 26% of patients willing to undergo additional treatment for a PFS benefit but no overall survival benefit, 71% of patients said they would undergo more treatment for a 6-month gain in overall survival.