Quality of life results and survival outcomes in trials of immunotherapy in advanced cancers: A systematic review and meta-research study

Background: Benefit in Quality of Life (QoL) might be overlooked in trials investigating immunotherapy. We examined QoL results in phase III randomized controlled trials (RCTs) investigating immune checkpoint inhibitors (ICIs) in advanced cancers and their correlation with overall survival (OS) and progression-free survival (PFS). Methods: We systematically reviewed articles of RCTs testing ICIs in advanced setting, published in PubMed-indexed journals up to 12/2023, reporting QoL results and at least one survival outcome between OS and PFS. We evaluated global QoL assessment in the experimental arm compared to the control arm. Also, we assessed whether OS and PFS were improved or not by experimental treatment. Fisher's exact test was used for statistical analysis. Results: 71/140 selected RCTs (50.7 %) met the inclusion criteria. Seven trials had two experimental arms for a total of 78 comparisons. Superior or inferior global QoL was found in 34/78 (43.6 %) and 1/78 (1.3 %) experimental arms, respectively. We found a statistically significant association between QoL and OS improvements (p = 0.0015), significant only in experimental arms testing ICIs alone (p = 0.0056). Instead, QoL results did not positively correlate with PFS (p = 0.0572), except for experimental arms composed of ICIs alone (p = 0.0309). Notably, experimental treatments failed to report superior QoL in 31/64 (48.4 %) arms with positive results. Conclusions: We found a positive association between QoL and survival outcomes in RCTs testing ICIs alone in metastatic cancers. Also, about half of the positive experimental treatments did not prompt QoL amelioration. This emphasizes the relevance of an accurate assessment of QoL in oncology RCTs.