Real-world comparison of the efficacy and safety of atezolizumab versus durvalumab in extensive-stage small cell lung cancer

Abstract

Background: Small cell lung cancer (SCLC) is an aggressive disease associated with high relapse rates and limited treatment options. Current standard of care treatment for extensive-stage disease includes combination chemotherapy plus immunotherapy. Programmed death ligand-1 (PD-L1) immune checkpoint inhibitors (ICIs) are preferred first-line treatments in combination with chemotherapy with both atezolizumab and durvalumab being equivalent options. Although both ICIs are listed as front-line options in clinical guidelines, there have been no head-to-head trials comparing durvalumab to atezolizumab. Therefore, it is unknown if either agent is superior with regards to efficacy or safety.

Methods: This retrospective, single-institution study examined patients with extensive-stage small cell lung cancer presenting to Moffitt Cancer Center between October 1st, 2018 to May 31st, 2023 who received either atezolizumab or durvalumab in combination with a platinum-doublet in the first-line setting. To be included in this analysis patients must have received at least two cycles of induction chemotherapy and ICI and one cycle of maintenance ICI. The primary outcome of this study was overall survival. The secondary outcomes include progression-free survival, immune-related adverse events, hospitalizations due to ICIs, and progression-free survival on second-line therapy (PFS2).

Results: Of the 101 patients included, 55 received durvalumab (54.5 %) and 46 received atezolizumab (45.5 %). The median overall survival in the durvalumab and atezolizumab arms were 14.7 versus 11.6 months, respectively (HR 0.59; 95 % CI, 0.38-0.92; P = 0.020). There was not a statistically significant difference in median progression-free survival between the two arms (6.3 versus 5.9 months, P = 0.344). Atezolizumab was associated with a numerically higher incidence of immune-related adverse events (47.8 % versus 32.7 %, P = 0.157) and hospitalization rates for those with an immune-related adverse event (36.4 % versus 16.7 %, P = 0.204). PFS2 was 2.3 months in the atezolizumab arm and 3.4 months in the durvalumab arm (HR 1.24; 95 % CI, 0.69-2.23; P = 0.466).

Conclusions: In this real-world retrospective study, durvalumab was associated with improved overall survival in patients with extensive-stage small cell lung cancer consistent with previous findings from a similar study in a Chinese patient population. Although not statistically significant, there was a lower incidence of immune-related adverse events in the durvalumab arm as well as ICI-related hospitalizations. PFS2 was not statistically significant different between arms.

Keywords: Atezolizumab; Durvalumab; Maintenance therapy; SCLC.