medwireNews: Progression-free survival (PFS) should not be used as a surrogate marker for health-related quality of life (HRQoL) as there is no correlation between them, results of a systematic review and quantitative analysis of randomized clinical trials show.
Feng Xie (McMaster University, Hamilton, Ontario, Canada) and co-authors say that their “findings raise questions about the assumption that interventions prolonging PFS also improve HRQoL in patients with cancer and suggest that HRQoL should be measured directly and accurately, with adequate follow-up time, in future studies.”
The study included 38 randomized clinical trials comprising 13,979 patients with 12 different cancer types. The trials, published between 2000 and 2016, included oral, intravenous, intraperitoneal, or intrapleural chemotherapy or biologic treatments and used six different instruments to assess HRQoL.
Almost three-quarters (74%) of the studies reported an improvement in PFS for the intervention versus the comparator. The mean difference in median PFS between the two groups was 1.91 months.
Improvements in HRQoL were observed in 53% of 30 trials reporting data for the global domain, 55% of 20 reporting on the physical domain, and 62% of 13 trials that included data for the emotional HRQoL domain.
When the researchers standardized HRQoL scores to a range of 0–100, with higher scores representing better HRQoL, they found that global HRQoL changed by an average of −0.39 points per month, physical HRQoL changed by 0.26 points per month, and emotional HRQoL changed by an average of 1.08 points per month.
Scatterplots of the relationship between PFS and each of the HRQoL domains showed no significant association between the two outcome measures, with slopes of 0.12, –0.20, and 0.78 for the associations between the difference in median PFS and the difference in change for global, physical, and emotional HRQoL, respectively.
Writing in JAMA Internal Medicine, Xie et al note that more than 60% of the trials had shorter follow-up for HRQoL than for PFS suggesting that they “may not have captured some HRQoL benefit attributable to PFS that could have occurred later,” potentially underestimating the association between PFS and HRQoL.
Nonetheless, the researchers say that their data “cast doubts” on the assumptions made by “PFS advocates [who] believe that PFS indicates disease control and stabilization, leading to reduction in disease symptoms, thus implying clinical benefit through improvement in HRQoL.”
The team concludes that future clinical trials with a primary PFS endpoint should also “be designed to provide high-quality findings regarding whether the interventions affect HRQoL, including adequate power and data quality (duration of follow-up and high patient compliance).”
They continue: “This approach will avoid assumptions and would make the relationship between PFS outcomes and HRQoL outcomes clear, allowing clinical judgment to assess benefits vs risks should the HRQoL outcomes be compromised by treatments that increase PFS.”
By Laura Cowen
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