Real-world efficacy of atezolizumab combined with etoposide and platinum chemotherapy in extensive-stage small cell lung cancer: a retrospective cohort study

Abstract

Background: Small cell lung cancer (SCLC) is a highly aggressive thoracic malignancy for which immune checkpoint inhibitors (ICIs) combined with chemotherapy have become standard first-line therapy according to recent randomized clinical trials. However, real-world data on the efficacy of atezolizumab-based regimens remain limited, especially in patients with high tumor burden or brain metastases. The aim of this study was to evaluate the real-world effectiveness of atezolizumab plus etoposide and platinum (EP) chemotherapy compared to EP alone as first-line treatment in patients with extensive-stage SCLC (ES-SCLC).

Methods: This retrospective cohort study included patients diagnosed with ES-SCLC at Tianjin Chest Hospital between January 2019 and December 2024. Eligible patients received either atezolizumab plus EP or EP chemotherapy alone as first-line treatment, with at least four completed cycles. Inverse probability of treatment weighting (IPTW) was used to balance the baseline covariates. The primary outcomes were overall survival (OS) and progression-free survival (PFS), which were analyzed with Kaplan-Meier curves and Cox proportional hazards models with robust variance estimation.

Results: A total of 95 patients were included (42 in the atezolizumab group and 53 in the EP-only group). After IPTW adjustment, the combination group demonstrated improved OS as compared to the EP-only group [median 9.7 vs. 7.1 months; hazard ratio (HR) =0.51, 95% confidence interval (CI): 0.30-0.94]; meanwhile, the PFS showed similar median values between the groups (5.8 vs. 5.7 months), but the immunotherapy group (atezolizumab plus etoposide and platinum) exhibited a delayed separation in survival curves and a favorable HR (0.42, 95% CI: 0.21-0.86), suggesting durable benefit. Subgroup analysis revealed significant OS and PFS benefits among patients without brain metastases, while results in the brain metastasis subgroup were inconclusive due to the limited sample size.

Conclusions: In this real-world cohort of patients with ES-SCLC, atezolizumab combined with EP chemotherapy was associated with improved survival outcomes as compared to EP alone, even in a clinically heterogeneous population. These findings support the broader applicability of immune-chemotherapy in routine practice and underscore the potential benefit for patients without brain metastases.

Keywords: Atezolizumab; extensive-stage small cell lung cancer (ES-SCLC); immune-chemotherapy; inverse probability of treatment weighting (IPTW); real-world study.

Figure 1

Flowchart of patient selection. A total of 247 patients were screened, and after the application of inclusion and exclusion criteria, 95 patients were included in the final analysis. EP, etoposide and platinum; ES-SCLC, extensive-stage small cell lung cancer.

Figure 2

SMD before and after IPTW adjustment. All covariates were balanced post-weighting (SMD <0.1). ECOG, Eastern Cooperative Oncology Group; IPTW, inverse probability of treatment weighting; SMD, standardized mean difference.

Figure 3

IPTW-weighted Kaplan-Meier curve for OS. The atezolizumab plus EP group showed prolonged OS as compared to the EP-only group (median 9.7 vs. 7.1 months; HR =0.51, 95% CI: 0.30–0.94). Baseline sample sizes were 42 in the atezolizumab + EP group and 53 in the EP-only group. CI, confidence interval; EP, etoposide and platinum; HR, hazard ratio; IPTW, inverse probability of treatment weighting; KM, Kaplan-Meier; OS, overall survival.

Figure 4

Unweighted Kaplan-Meier curve for OS. The immunotherapy group showed a trend toward improved survival (HR =0.54; P=0.050). Baseline sample sizes were 42 in the atezolizumab + EP group and 53 in the EP-only group. CI, confidence interval; EP, etoposide and platinum; HR, hazard ratio; KM, Kaplan-Meier; OS, overall survival.

Figure 5

IPTW-weighted Kaplan-Meier curve for PFS. A delayed separation was observed in the immunotherapy group (HR =0.42, 95% CI: 0.21–0.86). Baseline sample sizes were 42 in the atezolizumab + EP group and 53 in the EP-only group. CI, confidence interval; EP, etoposide and platinum; HR, hazard ratio; IPTW, inverse probability of treatment weighting; KM, Kaplan-Meier; PFS, progression-free survival.

Figure 6

Unweighted Kaplan-Meier curve for PFS. Although the median PFS was similar, the immunotherapy group showed a more favorable HR (HR =0.37, 95% CI: 0.18–0.77). Baseline sample sizes were 42 in the atezolizumab + EP group and 53 in the EP-only group. CI, confidence interval; EP, etoposide and platinum; HR, hazard ratio; KM, Kaplan-Meier; PFS, progression-free survival.

Figure 7

Subgroup analysis of OS in patients without brain metastases. Atezolizumab improved OS significantly (HR =0.47, 95% CI: 0.23–0.97). Baseline sample sizes were 42 in the atezolizumab + EP group and 53 in the EP-only group. CI, confidence interval; EP, etoposide and platinum; HR, hazard ratio; KM, Kaplan-Meier; OS, overall survival.

Figure 8

Subgroup analysis of PFS in patients without brain metastases. Delayed separation in survival curves favored the immunotherapy group (HR =0.33, 95% CI: 0.15–0.75). Baseline sample sizes were 42 in the atezolizumab + EP group and 53 in the EP-only group. CI, confidence interval; EP, etoposide and platinum; HR, hazard ratio; IPTW, inverse probability of treatment weighting; KM, Kaplan-Meier; PFS, progression-free survival.