P20 The impact of PD1 and PDL1 immunotherapy on NSCLC outcomes beyond overall survival: a systematic review

Introduction/Objectives Despite comprising many cancer diagnoses, few treatments are suitable for patients with advanced non-small-cell lung cancer (aNSCLC). Trials suggest blockade of Programmed Death 1 (PD1) or its ligand (PDL1) may be effective for improving overall survival among patients with aNSCLC. However, the impact of this therapy on outcomes other than survival and real-world outcomes remains largely unknown. Therefore, we investigated whether PD1 and PDL1 immunotherapy is more effective than chemotherapy and placebo, focussing on clinical outcomes beyond overall survival, and comparing real-world to trial outcomes. Methods In this systematic review, six databases were searched for randomised controlled trials (RCTs) and observational studies investigating nivolumab, pembrolizumab, atezolizumab or durvalumab. Study selection was performed independently by two reviewers. Data regarding overall survival, progression-free survival, adverse effects (AEs), quality of life (QoL) and cost-effectiveness were descriptively analysed. The extent to which RCT data was recapitulated by observational studies was assessed. Results From 5,423 search results, 139 full texts and abstracts were included. Immunotherapy was associated with a longer overall survival than chemotherapy and placebo; this benefit was sustained across study designs. In RCTs, the incidence of treatment-related AEs was approximately 20% lower among patients using immunotherapy compared to chemotherapy. However, no other consistent benefits were observed. Progression-free survival was inconsistent. The profile of AEs was similar between treatment arms in RCTs, and a broader range of AEs was observed in real world data. Improvements to QoL varied according to the instrument used; however, QoL was not recorded widely. The main difference between RCT and observational data was in the incidence of AEs; a lower treatment-related AE incidence was reported among observational studies. Discussion Despite benefits to overall survival, it is unclear whether PD1 and PDL1 immunotherapy is more effective than chemotherapy among patients with aNSCLC when considering other clinical outcomes. By considering both trial and real-world studies, these findings are significant in providing one of the most realistic estimates of treatment effectiveness to date. Given the expense associated with this therapy, our findings suggest future research should focus on identifying patients most likely to derive benefit.