medwireNews: Around a quarter of phase 3 randomized controlled trials for advanced cancer show an improvement in global quality of life (QoL) and this is significantly linked to improvements in overall survival (OS), Canadian researchers say.
However, finding no significant correlation between QoL benefit and progression-free survival (PFS), Bishal Gyawali and co-authors, from Queen’s University in Kingston, Ontario, advise that “improvement in QOL cannot be presumed based on improved PFS alone.”
The team reviewed the outcomes of 24,806 participants of 45 phase 3 trials published in 2019 that reported QoL data, including 13,368 advanced cancer patients in the experimental arm and 11,438 in the control arm.
The trials were designed to test targeted therapies (47%), cytotoxic agents (27%), immunotherapies (16%), or repurposed drugs (11%) in patients with lung (16%), ovarian (13%), breast (11%), or other types of cancer. Around half (51%) were double-blind, placebo controlled studies, with 38% reporting OS as a primary or co-primary endpoint and 62% PFS. The majority (80%) of trials had full or partial industry funding.
Overall, 24% of the trials reported an improvement in global QoL with use of the experimental versus control agent, as measured by EORTC, FACT, EuroQoL, or other QoL tools on at least one occasion during treatment. A further 62% reported unchanged QoL during the treatment and 13% reported inferior QoL in the experimental arm.
Trials demonstrating QoL benefits were significantly more likely to achieve an improvement in OS versus those without (64% of 11 vs 29% of 34 trials) but this was not true for PFS (55 vs 50%).
And while none of the six trials with inferior QoL in the experimental arm showed an OS improvement, four of these did show PFS gains, the investigators say.
Gyawali and co-workers observe that three of the six trials with inferior QoL were testing targeted agents, two were looking at repurposed drugs, and one was investigating a cytotoxic agent; QoL was improved in 54% of 11 trials investigating an immunotherapy agent.
“[M]any physicians and patients believe that targeted drugs and immunotherapies are preferable owing to their perceived positive effect on patients’ QOL compared with cytotoxic agents,” the investigators observe.
“Although the present results for immunotherapy drugs were consistent with these perceptions, we found that worsening of QOL was more common with targeted drugs than with cytotoxic agents,” they say, and therefore recommend that “physicians and patients should keep in mind that a chemotherapy-free regimen does not necessarily mean better QOL.”
Of concern, the researchers say that three of the six trials with inferior QoL findings “seemed to downplay those outcomes by describing them as not clinically significant despite being statistically significant,” and these studies did not define in advance the terms “clinically significant” or “small differences.”
Furthermore, 54% of 28 trials with no change in QoL described their findings in a “neutral frame” but 47% were reported as having a “favorable” framing of outcomes, such as QoL being described as maintained, preserved, or not adversely affected.
“Thus, favorable reporting of QOL results was present in 16 of 34 (47%) trials with unimproved QOL outcomes,” say Gyawali et al, and this was significantly more common in the trials with industry funding than those with public funding (60% of 25 vs 11% of nine trials).
“Using phrases such as ‘no detrimental effects on QOL’ or ‘without adversely affecting QOL’ to describe unimproved QOL should be avoided, especially in the advanced or metastatic setting because the only reason for patients to undergo cancer treatment in the advanced setting (in the absence of OS gains) would be to have a better QOL or relief from cancer symptoms,” the researchers emphasize.
They therefore “strongly recommend that trial publications report no difference in QOL in a neutral frame, such as ‘unchanged QOL’ rather than ‘not worse.’”
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