Continued Atezolizumab Shows Durable Benefit in Pretreated ES-SCLC

"Our pooled analysis supports atezolizumab continuation as a viable [second-line] treatment for [patients with] ES-SCLC, contributing to the standardization of [immune checkpoint inhibitor] continuation protocols," according to the study authors.

Continuation therapy with atezolizumab (Tecentriq) following progression on first-line chemo-immunotherapy produced promising efficacy and manageable safety in a small cohort of patients with extensive-stage small cell lung cancer (ES-SCLC), according to findings from a pooled analysis study published in Clinical and Experimental Medicine.¹

Data showed a median overall survival (OS) of 18.87 months (95% CI, 15.28-22.45), and the median progression-free survival (PFS) with second-line atezolizumab was 4.07 months (95% CI, 1.15-6.98). According to univariate analysis, factors that significantly correlated with prognosis included primary liver metastasis (HR, 0.12; P <.01) and frontline therapy response (HR, 3.16; P = .03; HR, 22.39; P <.01).

Independent factors that affected OS per multivariate analysis included baseline liver metastasis (HR, 0.13; P = .02), progression-free interval (HR, 12.51; P <.01), and depth of response during frontline chemo-immunotherapy (HR, 53.13; P <.01). Subgroup analysis highlighted a median OS of 8.68 (95% CI, 7.27-10.09) months for patients in the short-term response group—which included those with a PFS of less than 6 months to first-line therapy—and 19.98 months (95% CI, 14.91-25.05) in the long-term response group—which included those with a PFS of 6 months or longer to first-line treatment (P = .021). In patients with a depth of response of at least 29% and less than 29% to frontline therapy, the median OS was 21.84 months (95% CI, 12.91-31.41) and 14.63 months (95% CI, 9.64-19.62), respectively (P <.001).

“In our pooled analysis of patients with ES-SCLC who progressed after [first-line] immunotherapy, the continuation of atezolizumab showed promising antitumor activity with durable clinical benefit,” lead study author Wenhao Shi, from the Department of Cancer Center at The Second Affiliated Hospital of Chongqing Medical University and Chongqing Key Laboratory of Immunotherapy, wrote with coauthors.¹ “Our pooled analysis supports atezolizumab continuation as a viable [second-line] treatment for [patients with] ES-SCLC, contributing to the standardization of [immune checkpoint inhibitor] continuation protocols.”

According to the study authors, data from the phase 1/3 IMpower133 trial (NCT02763579) showed that combining atezolizumab with chemotherapy as a frontline treatment could significantly improve survival in patients with ES-SCLC.² Due to limited long-term benefits with initial atezolizumab-containing treatment based on disease progression and resistance, however, investigators noted an unmet need for effective subsequent therapy for patients with ES-SCLC who experience progression following first-line chemoimmunotherapy.

Investigators of this retrospective cohort study assessed patients with ES-SCLC who underwent treatment at 6 centers from January 2020 to April 2024 to assess the tolerability and survival outcomes associated with continued atezolizumab after progression on frontline chemoimmunotherapy. Patients with histologically or cytologically confirmed SCLC and confirmed extensive-stage disease characterized by distant metastasis or thoracic extension beyond 1 radiation port were eligible for inclusion in the analysis.

Efficacy end points included median OS, median PFS, and depth of response. Investigators also evaluated safety and severity of adverse effects (AEs) based on CTCAE v5.0 criteria.

The median patient age was 65 years (IQR, 55.3-69.0), with most being over 60 years (64.3%) and male (85.7%). Additionally, most patients had smoking history (78.6%), a body mass index of 18.5 to 23.9 (57.1%), a performance status of 1 (64.3%), no prior consolidative thoracic radiotherapy (57.1%), baseline brain metastases (53.6%), no baseline liver metastases (67.9%), and anti-angiogenesis therapy in the second-line setting (39.3%).

All patients (100.0%) experienced AEs of any grade, with the most common including cough (35.7%), dyspnea (35.7%), pneumonitis (35.7%), decreased appetite (35.7%), and nausea (32.1%). Grade 3 to 5 AEs affected 14.3% of the population; the most common toxicity of this severity was decreased appetite (7.1%). Additionally, 21.5% of patients had immune-related AEs, which included immune-related thyroiditis in 17.9%.

References

1. Shi W, Bao X, Xiong J, et al. Efficacy and safety analysis of atezolizumab continuation beyond progression in extensive‑stage small cell lung cancer. Clin Exp Med. 2025; Mar;25(1):71. doi:10.1007/s10238-025-01606-1
2. Liu SV, Reck M, Mansfield AS, et al. Updated overall survival and PD-L1 subgroup analysis of patients with extensive-stage small-cell lung cancer treated with atezolizumab, carboplatin, and etoposide (IMpower133). J Clin Oncol. 2021;39(6):619-630. doi:10.1200/JCO.20.01055