P48.10 Chemo-Immunotherapy in the Frontline of Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Indirect Comparisons

Abstract

For decades platinum-doublet chemotherapy (CT) has represented the standard of care for extensive stage Small Cell Lung Cancer (ES-SCLC) patients. More recently, the addition of an immune checkpoint inhibitor (ICI) to standard CT has shown to improve survival in patients with treatment-naïve ES-SCLC. The current work aims to assess any difference in both efficacy and safety profiles among different Immuno-Oncology (IO) agents in combination with platinum-based CT in ES-SCLC patients according to different ICIs subtypes. We performed a systematic review (MEDLINE, Cochrane database, meetings abstracts) and finally included in our metanalysis six first-line randomized controlled trials (Reck et al 2013, Reck et al 2016, IMpower 133, EA5161, KEYNOTE-604, CASPIAN) comparing the association of standard CT (carboplatin plus paclitaxel or cisplatin/carboplatin plus etoposide) with an ICI (ipilimumab, nivolumab, pembrolizumab or durvalumab) versus standard CT alone in ES-SCLC. Pooled hazard ratios (HRs) and risk ratios (RRs) for progression-free survival (PFS), overall survival (OS), objective response rates (ORR), 12-month duration of response rate (DORR), treatment-related adverse events (TRAEs) and discontinuation rates (DRs) were obtained. Although no clear advantage in terms of ORR was directly underlined, our pooled results showed how the addition of ICIs to CT significantly improved DORR (RR 4.45 , 95% CI 1.76 – 11.21), resulting in long term benefits in PFS (HR 0.80, 95% CI 0.73 – 0.86) and OS (HR 0.82, 95% CI 0.75 – 0.90) with no differences in terms of TRAEs or DRs. Of note, indirect comparisons according to the different IO strategies suggested a slight advantage in favor of both PD-1 and PD-L1 over anti-CTLA-4 agents in terms of efficacy outcomes along with no additional significant differences in the safety profile, respectively (Figure 1a-b). When indirectly comparing PD-1 with PD-L1 inhibitors, no relevant significant differences regarding both efficacy and safety endpoints were observed, with benefit trends only for DORR (RR 1.86, 95% CI 0.52 – 6.69) and DR (RR 0.49, 95% CI 0.15 – 1.61) in favor of anti-PD-1 over anti-PD-L1 (Figure 1c). Based on the pooled results of our meta-analysis, the association of an ICI with CT confirmed to provide a survival benefit when compared to CT alone. Although chemo-immunotherapy would now represent an established standard for newly diagnosed ES-SCLC patients, establishing the optimal therapeutic options still addresses an unmet need in the clinical setting and predictive biomarkers eventually need to be identified.