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, Ontario, Canada, told Medscape Medical News.
Even with an overall survival benefit, 1 in 5 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, California, 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 Lee, associate editor (palliative care) for Cancer.Net, the American Society of Clinical Oncology (ASCO) patient information website.
The study was published online Juy 17 in the Journal of the National Cancer Institute.
Although PFS is often used as a primary endpoint in cancer drug trials, evidence indicates that PFS is typically a poor surrogate both for overall survival and quality of life. 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, Booth and colleagues wanted to better understand patients' attitudes towards 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 to 9 months.
About 1 in 6 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.
Notably, about 1 in 5 participants (21%) said they would decline additional treatment even with a 6-month overall survival benefit, reflecting the "limited value of added time if quality of life was compromised," the authors explained.
Weighing the Benefits of More Treatment
Overall, the findings suggest that while some patients are willing to undergo more toxic treatment regardless of PFS outcomes, most prefer to explicitly weigh the benefits of PFS, overall survival, and quality of life, Booth and colleagues said.
The findings also make clear the need to design randomized clinical trials that focus on endpoints and the gains that are of greatest value to patients.
"While there are a handful of circumstances in which PFS is a valid surrogate for overall survival, this is the exception and not the rule," said Booth, who, along with colleagues, recently launched a global movement called Common Sense Oncology to help make cancer care and clinical trials more patient-centered.
Drug companies like the PFS measure because it gives an answer quickly. "They don't have to wait for the overall survival surrogate," but in many cases, PFS is not a good primary endpoint, said Lee.
The exception, he noted, would be for some slow-growing cancers, such as low-grade prostate cancer, in which overall survival takes 10 years to gauge. "But outside of those few cancers, we need to stick to overall survival as the gold standard, and patients are basically telling us the same," Lee explained.
What about a treatment that might not extend overall survival but could improve quality of life?
"It is easy to measure a year in life, but what about the life within a year," Rachel Koven, MSc, author and patient advocate, Queen's University Cancer Research Institute, told Medscape Medical News. "Beyond the potential for an extended number of days, what constitutes a 'good' day or a day well lived, and are the treatment decisions impacting that? While this may be different for each person, regardless of the definition used, it will still be of the utmost importance for all."
Overall, Lee stressed, it's important for oncologists to inform patients about what trial results show.
"We have to talk to patients and tell them a drug has shown progression-free improvement but not an overall survival benefit. That absolutely needs to be included in the discussion so that patients can give full, informed consent to what the treatment options are," he said.
Koven agrees. "We must continuously strive to improve doctor-patient communication to ensure that patients facing incurable cancer can make evidence-based choices that match their unique goals, preferences, and needs," she said.
"It is essential that care plans be created with outcomes that matter," Koven told Medscape Medical News. "Treatments with small benefits lead to lost time for patients spent at the cancer center rather than with family and friends."
The study was supported by the Canadian Institutes of Health Research. Booth, Koven and Lee have no relevant disclosures.
J Natl Cancer Inst. Published online July 17, 2023. Abstract
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Cite this: Survival, QoL Trump PFS for Most Patients With Cancer - Medscape - Jul 28, 2023.
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