Effect of the number of induction chemotherapy cycles on the efficacy of first-line atezolizumab combined with chemotherapy in extensive-stage small cell lung cancer

Abstract

Background: Compared with chemotherapy alone, the addition of atezolizumab to the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) improves the overall survival (OS), but the benefit remains limited. This study aims at investigating the factors influencing prognosis and to assess the effect of the number of induction chemotherapy cycles on treatment efficacy.

Methods: We retrospectively analyzed the data of patients with ES-SCLC treated in five centers between March 2020 and September 2022. All 45 patients received first-line treatment with etoposide plus platinum combined with atezolizumab. The primary endpoints were progression-free survival (PFS) and OS in the total population and subpopulations based on the number of induction chemotherapy cycles. Least absolute shrinkage and selection operator (LASSO) regression were applied to identify the prognostic variables, and the effect of varying the number of induction chemotherapy cycles on the treatment efficacy was evaluated.

Results: A total of 45 patients were enrolled in the study. The median PFS for the first-line treatment was 7 months, and the median OS was 17.6 months. The following 10 variables were analyzed using LASSO regression: gender, age, liver metastasis, bone metastasis, brain metastasis, number of first-line induction chemotherapy cycles, first-line immunotherapy maintenance, receipt of cross-line immunotherapy, chest radiotherapy, and brain radiotherapy. The analysis revealed that receiving ≥6 cycles of induction chemotherapy was the most important variable affecting prognosis and the only one significant [concordance index: 0.658; hazard ratio: 0.32 (95% confidence interval: 0.17-0.63)]. Patients who received ≥6 cycles of induction chemotherapy (n=25) had a longer median PFS (8 vs. 5 months) and median OS (18.5 vs. 13.1 months) than those who received <6 cycles (n=20). Subgroup analyses indicated consistent survival benefits of ≥6 induction chemotherapy cycles across key subgroups, including males, patients aged ≤65 years, and those with or without brain metastasis (all P value <0.05).

Conclusions: Receiving ≥6 cycles of induction chemotherapy significantly prolonged the median PFS and median OS of patients, highlighting its crucial factor influencing the efficacy of first-line atezolizumab combined with chemotherapy in patients with ES-SCLC.

Keywords: Atezolizumab; cycles; extensive-stage small cell lung cancer (ES-SCLC); induction chemotherapy.

Figure 1

Kaplan-Meier plots for PFS (A) and OS (B) in the overall population. CI, confidence interval; mOS, median overall survival; mPFS, median progression-free survival; OS, overall survival; PFS, progression-free survival.

Figure 2

The LASSO regression analysis was employed to identify significant prognostic variables. The best regularization parameter (λ value) in the cross-validation graph (A). The regularization path graph (B) showed that ≥6 cycles of induction chemotherapy was the most crucial variable. LASSO, least absolute shrinkage and selection operator.

Figure 3

Kaplan-Meier plots showed that both PFS (A) and OS (B) were significantly better in the ≥6 cycles of induction chemotherapy group than the <6 cycles of induction chemotherapy group. OS, overall survival; PFS, progression-free survival.

Figure 4

Forest plot showing that the patients who received ≥6 cycles of induction chemotherapy had better survival outcomes across most subgroups. Bone.met, bone metastasis; Brain.met, brain metastasis; Brain.radio, brain radiotherapy; Chest.radio, chest radiotherapy; CI, confidence interval; HR, hazard ratio; IC.cycles, induction chemotherapy cycles; IO.cross-line, cross-line immunotherapy; IO.maint, immunotherapy maintenance; Liver.met, liver metastasis.