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. 2022 Sep 26:2022:3645489.
doi: 10.1155/2022/3645489. eCollection 2022.

Efficacy and Safety of PD-L1 Inhibitors plus Chemotherapy versus Chemotherapy Alone in First-Line Treatment of Extensive-Stage Small-Cell Lung Cancer: A Retrospective Real-World Study

Jingjing Qu  1   2 , Farhin Shaheed Kalyani  1 , Qian Shen  1   2 , Guangdie Yang  1   2 , Tianli Cheng  3 , Li Liu  4 , Jianya Zhou  1   2 , Jianying Zhou  1   2
Affiliations

Efficacy and Safety of PD-L1 Inhibitors plus Chemotherapy versus Chemotherapy Alone in First-Line Treatment of Extensive-Stage Small-Cell Lung Cancer: A Retrospective Real-World Study

Jingjing Qu et al. J Oncol. .

Abstract

Background: Most patients with small-cell lung cancer (SCLC) have extensive-stage (ES) disease with a poor prognosis. Immunotherapy has shown good therapeutic effects in the treatment of ES-SCLC. We performed a real-world retrospective study to evaluate the safety and efficacy of PD-L1 inhibitors plus chemotherapy in patients with ES-SCLC.

Method: A total of 224 patients diagnosed with ES-SCLC between March 2017 and April 2021 were included, of which 115 received only etoposide-platinum (EP) chemotherapy,and 109 received programmed cell-death ligand 1 (PD-L1) inhibitors and EP.

Results: Immune checkpoint inhibitors (ICIs) plus platinum were associated with a significant improvement in overall survival (OS), with a hazard ratio (HR) of 0.60 (95% CI, 0.42-0.85; P=0.0054); median OS was 19 months in the ICIs plus EP group vs. 12 months in the EP group. The median progression-free survival (PFS) was 8.5 and 5.0 months, respectively (HR for disease progression or death, 0.42; 95% CI, 0.31-0.57; P < 0.0001). Male patients <65 years old, Stage IV, PS 0-1, without liver and brain metastasis had a better OS in the ICIs plus EP group than the EP group. The PFS and OS in the durvalumab plus chemotherapy group were insignificantly longer than that of the atezolizumab plus chemotherapy group. Any adverse effects (AEs) of grade 3 or 4 occurred in 50 patients (45.9%) in the ICIs plus EP group and 48 patients (41.7%) in the EP alone group. The most common immune-related AEs (irAEs) were immune hypothyroidism events (17.1%, 7/41), immune dermatitis (9.8%, 4/41), and immune pneumonia (9.8%, 4/41) in the durvalumab plus platinum-etoposide group. Immune liver insufficiency (10.3%, 7/68) and immune hypothyroidism (8.8%, 6/68) were the most common irAEs in the atezolizumab plus platinum-etoposide group.

Conclusion: This study shows that adding PD-L1 inhibitors to chemotherapy can significantly improve PFS and OS in patients with ES-SCLC and demonstrates its safety without additional AEs.

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Conflict of interest statement

The authors declare there are no conflicts of interest.

Figures

Figure 1
Figure 1
Overall survival (OS) and progression-free survival (PFS) in the ICIs combination chemotherapy cohort and only chemotherapy cohort. (a) Kaplan–Meier graph of OS in the two groups. (b) Kaplan–Meier graph of PFS in the two groups.
Figure 2
Figure 2
Forest plot of subgroup analysis of OS and PFS. (a) Forest plot of subgroup analysis of OS. (b) Forest plot of subgroup analysis of PFS. ICI: immune-checkpoint inhibitor; CH: chemotherapy; extensive a stage IIIb–IIIc; extensive b stage IV.
Figure 3
Figure 3
Overall survival (OS) and progression-free survival (PFS) in the durvalumab plus chemotherapy group and atezolizumab plus chemotherapy group. (a) Kaplan–Meier graph of PFS in the two groups. (b) Kaplan–Meier graph of OS in the two groups.
Figure 4
Figure 4
Targeting ICIs therapy for ES-SCLC and challenge for ICIs-based treatment in ES-SCLC. T cells blocked by anti-PD-1, anti-PD-L1, and anti-CTLA-4 agents, which interact with ES-SCLCs, and T cells medicate an effective role in killing ES-SCLCs. The current studies are limited by tumor metastases to other organs, high frequency of AEs, lack of accurate combination therapy, and resistance to anti-ICI treatment. ICI, immune checkpoint inhibitor; CTLA-4, cytotoxic T-lymphocyteantigen-4; PD-1, programmed cell death 1; PD-L1, programmed cell death ligand 1; SCLC, small-cell lung cancer; ES-SCLC; extensive-stage SCLC; APC, antigen presenting cell; TCR, T cell receptor; MHC, major histocompatibility complex; AEs, adverse events.
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