Better PFS may not mean better HRQOL


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Preparing drug for a trial

Cancer treatments that prolong progression-free survival (PFS) may not improve health-related quality of life (HRQOL), researchers reported in JAMA Internal Medicine.

The researchers failed to find a significant association between PFS and HRQOL in an analysis of cancer clinical trials.

“There are only two reasons to use progression-free survival as a valid endpoint in oncology,” said study author Feng Xie, PhD, of McMaster University in Hamilton, Ontario, Canada.

“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.”

“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 benefit.”

With this in mind, Dr. Xie and his colleagues conducted a review and meta-analysis of 52 articles reporting on 38 randomized clinical trials. The trials included 13,979 patients with 12 types of cancer, including 1 trial of patients with multiple myeloma.

The median follow-up in these trials ranged from 10.5 months to 66.0 months.

The median PFS of patients who received the trial interventions ranged from 1.8 months to 33.7 months.

For 28 of the trials (74%), patients who received the trial intervention had better PFS than patients who received the comparator. Overall, the mean difference in median PFS between the intervention and comparator arms was 1.91 months.

HRQOL was measured with 6 different instruments* across the trials, and the types of HRQOL measured varied. Thirty trials included global HRQOL, 20 included physical, and 13 included emotional HRQOL. The duration of reported or measured HRQOL ranged from 1 month to 34 months.

Improved global HRQOL was reported in 53% of trials (16/30), improved physical HRQOL was reported in 55% (11/20), and improved emotional HRQOL was reported in 62% (8/13). The mean difference in change of HRQOL adjusted to per-month values was −0.39 for global, 0.26 for physical, and 1.08 for emotional HRQOL.

The slope of the association between the difference in median PFS and the difference in HRQOL change was:

  • 0.12 (95% confidence interval [CI], −0.27 to 0.52) for global HRQOL
  • −0.20 (95% CI,−0.62 to 0.23) for physical HRQOL
  • 0.78 (95% CI, −0.05 to 1.60) for emotional HRQOL.

Dr. Xie and his colleagues said these results suggest there is no significant association between PFS and HRQOL, so interventions prolonging PFS may not improve HRQOL.

“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,” Dr. Xie said.

He also argued for the need to “revisit this issue of using surrogate outcomes to measure the safety and efficacy of new oncology drugs.”

Dr. Xie and his colleagues did not report any conflicts of interest. One study author (Marcin Waligora, PhD) reported funding from the National Science Centre in Poland.

*EORTC-QLQ-C30, FACT-G19, Lung Cancer Symptom Scale, EQ-5D, 8-item linear analog self-assessment (LASA) questionnaire, and clinician-reported Karnofsky score

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