58P Treatment combinations in non-driver mutated mNSCLC: A systematic review and Bayesian network meta-analysis

To compare the relative survival benefits & toxicities among treatments for non-driver mutated metastatic NSCLC (mNSCLC). RCTs since inception, to June 1st 2021, were systematically searched from databases, trial registries & annual meeting abstracts. All trials comparing survival & toxicity between at least two of the following treatments were included: chemotherapy (CT) (single/multi-agent); PD1, PDL1 or CTLA4 immune checkpoint inhibitors (ICI) (single/multiagent) (with/without CT), &; radiotherapy followed by either chemotherapy (RT+CT) or immune checkpoint inhibitors. The primary outcomes were risk of death at 1 year, risk of progression at 6 months & 1 year, & overall grade 3 or higher (G3+) toxicities. A Bayesian network meta-analysis using a random-effects model & empirical Markov Chain Monte Carlo simulation of multiple interventions was used. Results were expressed as risk ratios (RR)[95% Credible Interval (CrI)] & ranked using SUCRA scores. All CT regimens were merged into a single category & ICIs were divided into two categories (PD1 or PDL1; CTLA-4). Local & global consistency and sensitivity analyses were performed on the network (after splitting treatments). All treatments satisfied the transitivity assumption. Risk-of-bias (RoB) & confidence were assessed with Cochrane RoB & CiNeMA tools. 30 RCTs (n = 14904; 36 possible comparisons; 12 direct comparisons) comparing 9 treatments were included. The combination of RT+PD1/PDL1 was ranked highest & demonstrated the lowest risk of death [RR = 0.47 (0.30–0.72)][SUCRA = 95%], progression [6 m RR = 0.39 (0.23–0.63)[SUCRA= 96%]; 1 yr RR= 0.74 (0.59–0.95)][SUCRA = 87%], & G3+ toxicities [RR = 0.74 (0.57–0.96)][SUCRA = 81%]. Results are shown below [RR (95% CrI)]. All sensitivity analyses favored RT +PD1/PDL1 over other treatments. The results suggest that combining RT with PD1/PDL1 inhibitors could improve outcomes over other treatments in non-driver mutated metastatic NSCLC.