Patient-Reported Outcomes with PD-1/PD-L1 Inhibitors for Advanced Cancer: A Meta-Analysis

Background The aim of this meta-analysis was to compare patient-reported outcomes (PROs) between programmed death receptor-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors and standard-of-care therapy in patients with advanced cancer. Methods We searched randomized controlled trials (RCTs) comparing single-agent PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, atezolizumab, avelumab, or durvalumab) with standard-of-care therapy in patients with advanced cancer reporting PROs with generic measures: the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (QLQ-C30) and the EuroQol Five Dimensions Questionnaire. The summary outcomes were changes in PROs from baseline to follow-up within and between treatment groups and time to deterioration (TTD) in PROs based on clinically meaningful change. Results A total of 6,334 patients from 13 RCTs were included: six nivolumab, five pembrolizumab, and two atezolizumab trials. For the QLQ-C30 global health status/quality of life, the pooled difference in mean change between treatment groups was 5.1 (95% confidence interval [CI], 3.3-6.9; p < .001) favoring PD-1/PD-L1 inhibitors. The pooled mean change from baseline in PD-1/PD-L1 inhibitors and controls was 0.1 (95% CI, -2.2, 2.5) and - 6.1 (95% CI, -8.4, -3.8), respectively. The TTD was significantly longer with PD-1/PD-L1 inhibitors, with a hazard ratio of 0.72 (95% CI, 0.55-0.93; p = .011). Similarly, significantly better outcomes were noted with PD-1/PD-L1 inhibitors on most of the other PRO measures. Conclusion PD1/PD-L1 inhibitors maintained health-related quality of life to a greater degree and had less worsening in symptoms than standard-of-care therapy even though patients on these immune modulators were on treatment longer. The better PRO profile further supports the clinical benefit of this treatment strategy for advanced cancer. Implications for Practice We conducted a systematic review and meta-analysis to compare patient-reported outcomes (PROs) of programmed death receptor-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors and standard-of-care therapy in patients with advanced cancer. PD-1/PD-L1 inhibitors were associated with consistently smaller PRO score deterioration from baseline to follow-up for different health-related quality-of-life and symptoms scales. In addition, the time to deterioration in multiple PRO domains was significantly longer with PD-1/PD-L1 inhibitors. Taken together, these findings indicate that the patients treated with PD-1/PD-L1 inhibitors maintained health-related quality of life to a greater degree and had less symptom burden compared with those treated with standard-of-care therapy.