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Progression-Free Survival and Health-Related Quality of Life in Randomized Clinical Trials

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Key Points

  • The mean difference in median PFS between the intervention and the control arms was 1.91 (3.35) months.
  • The mean differences in change of HRQoL adjusted to per-month values were −0.39 (3.59) for the global domain, 0.26 (5.56) for the physical domain, and 1.08 (3.49) for the emotional domain.
  • The results suggest future studies include rigorous and trustworthy measurement of HRQoL in cancer trials.

A review and analysis of randomized clinical trials published by Kovic et al in JAMA Internal Medicine questioned whether interventions that prolong progression-free survival (PFS) in patients with cancer improve their health-related quality of life (HRQoL).

The systematic review and quantitative analysis of 52 articles reporting on 38 randomized clinical trials involving 13,979 patients across 12 cancer types revealed no significant association between PFS and HRQoL.  

“Given the increased use of [PFS] 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 benefit,” said senior study author Feng Xie, PhD, Professor of the Department of Health Research Methods, Evidence, and Impact at McMaster University.

The research team conducted the review of randomized clinical trials of patients with cancer published from January 2000 to May 2016, screening 35,960 records. To increase comprehensiveness of the study, the researchers included a list of drugs approved by the U.S. Food and Drug Administration (FDA) based on PFS benefit, and set no language limitations.

Originally developed as a measurement tool to identify activity in the early development of drugs, PFS has become a widely-used surrogate outcome in cancer clinical trials. The increasing use of this measurement is also reflected in drug regulatory approvals.

“There are only two reasons to use progression-free survival as a valid endpoint in oncology,” said Dr. Xie. “One is that it is a valid surrogate marker for overall survival. The second is the assumption that patients who live longer without disease progression will have better health-related quality of life, even without longer survival.”

Findings

The mean difference in median PFS between the intervention and the control arms was 1.91 (3.35) months. The mean differences in change of HRQoL adjusted to per-month values were −0.39 (3.59) for the global domain, 0.26 (5.56) for the physical domain, and 1.08 (3.49) for the emotional domain. The slope of the association between the difference in median PFS and the difference in change for global HRQoL (n = 30 trials) was 0.12 (95% confidence interval [CI] = −0.27 to 0.52); for physical HRQoL (n = 20 trials) it was −0.20 (95% CI = −0.62 to 0.23); and for emotional HRQoL (n = 13 trials) it was 0.78 (95% CI = −0.05 to 1.60).

The results suggest future studies include rigorous and trustworthy measurement of HRQoL in cancer trials.

“Access to these types of drugs is costing our health-care 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,” Dr. Xie said.

“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.”

Within the scientific research community, Dr. Xie argued for the need to “revisit this issue of using surrogate outcomes to measure the safety and efficacy of new oncology drugs.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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