Comparative efficacy and safety of immunotherapy for advanced NSCLC: A systematic review and network meta-analysis.

Abstract

e21028 Background: Advanced non-small cell lung cancer (NSCLC) patients responded differently to checkpoint inhibitors (ICIs) therapy, leading to the confuse of choosing the optimal regimens for patients. Therefore, we performed this network meta-analysis to compare different agents across clinical trials. Methods: We searched databases, including EMBASE, PubMed, ClinicalTrials and etc, for abstracts, full-text articles and minutes of the annual meetings published from database inception through Oct 01, 2021. Phase 3 randomized clinical trials (RCTs) of first-line immunotherapy or combinations for adcanced (stage III/IV or recurrent) NSCLC were included. We selected 26 trials evaluating different ICIs (Atezolizuma (atezo), Pembrolizumab (pem), Nivolumab(nivo), Durvalumab (durva), Camrelizumab (camre), Tislelizumab (tisle), Sintilimab (sint), Sugemalimab (suge), Toripalimab (tori), Cemiplimab (cemip)) and combinations based on them. Primary outcomes of interests were overall survival (OS) and progression-free survival (PFS). Secondary outcomes of interests were objective response rate (ORR), and adverse events (AEs). Hazard ratio (HRs) and 95% confidence intervals (CI) were used to represent the results of OS and PFS. The subgroup analysis (pathological type, PD-L1 expression, gender, smoking history, ECOG score, metastasis status and ethnicity) was performed and the treatments were ranked in it and overall population. Results: In our study, all ICIs-based regimens had benefit in OS and PFS compared with chemotherapy. The network meta-analysis for OS showed the combination of Camre-Chemo ranked 1st in overall population, and most of dual ICIs-based regimens, except Nivo-Ipi-Chemo, showed minor improvement in OS while possess more safety concerns compared with other regimens. Atezo-Beva-Chemo (ranked 1st in PFS, 20th in safety), has shown good efficacy but was revealed with lower safety. Sint-Chemo demonstrated promising efficacy in PFS, but it remains to be seen whether the effectiveness could be transformed into OS benefit due to the lack of related data. Pem-Chemo (ranked 1st in ORR) demonstrated the best response to tumors in all treatments regardless of PD-L1 expression. In subgroup analysis, for patients with poor health conditions (≥65 years or with ECOG = 1), multi-drug combination regimens, such as Nivo-Ipi-Chemo and Atezo-Beva-Chemo, showed better benefits in PFS and OS compared with only chemo but had no significant advantages than any other treatments. Conclusions: In our study, we provide relative comprehensive results for latest researches of first-line ICIs. Overall, Care-Chemo, Pem-Chemo, Sint-Chemo, are prior to be recommended according to our study.