# Clinical outcomes and safety of continuous immunotherapy beyond progression in patients with extensive-stage small cell lung cancer: a retrospective real-world study

**Authors:** Chengjun Wang, Tiantian Xuan, Yanan Wang, Chuang Yang, Wen Zhao, Rongyu Zhang, Xue Meng, Jisheng Li

PMC · DOI: 10.3389/fimmu.2025.1681545 · Frontiers in Immunology · 2026-02-06

## TL;DR

This study examines the effectiveness of continuing immunotherapy after disease progression in patients with extensive-stage small cell lung cancer, finding some benefits but no overall survival improvement.

## Contribution

The study provides real-world evidence on the clinical outcomes of continuous immunotherapy beyond progression in extensive-stage small cell lung cancer.

## Key findings

- Continuous immunotherapy beyond progression shows a trend of prolonging second-line progression-free survival.
- The I+C+A group had the longest second-line progression-free survival of 4.60 months.
- Chemotherapy remains a cornerstone in second-line treatment with no significant differences in overall survival between groups.

## Abstract

Immunochemotherapy has been approved as first-line treatment for extensive-stage small cell lung cancer. However, second-line treatment options and whether continuous immunotherapy will improve clinical outcome are still controversial. This multi-center retrospective study aimed to investigate the efficacy of continuous immunotherapy for the patients who suffered progression from first-line immunochemotherapy.

We retrospectively reviewed the medical records of patients with extensive-stage small cell lung cancer treated with first-line immunochemotherapy in three major medical centers in Shandong Province. The patients enrolled achieved disease control during first-line immunochemotherapy but subsequently suffered disease progression.

From January 2020 to December 2024, a total of 354 patients treated with first-line immunochemotherapy were enrolled. The first-line progression free survival was 6.60 (95%CI: 6.28-6.92) months. A total of 206 patients were enrolled to compare the efficacy of second-line therapies, including chemotherapy alone (C, 40 cases), chemotherapy + anti-angiogenic therapy (C+A, 17 cases), immunochemotherapy (I+C, 122 cases), immunotherapy + anti-angiogenic therapy (I+A, 11 cases) and immunochemotherapy + anti-angiogenic therapy (I+C+A, 16 cases). Therein, I+C+A group obtained the longest second-line progression free survival of 4.60 (95%CI: 2.71-6.50) months. The second-line progression free survival of I+C group was also longer than that of the C group (3.50, 95%CI: 3.07-3.93 vs 2.33, 95%CI: 1.66-3.01). Regarding overall survival, I+A group achieved the longest overall survival of 22.00 (95%CI: 11.39-32.61) months compared with 19.53 (95%CI: 16.81-22.26) months for I+C group. However, there were no statistical differences in second-line progression free survival and overall survival among the groups. In terms of safety, the rates of adverse events in the I+C and C groups were not statistically significant.

Continuous immunotherapy beyond progression in extensive-stage small cell lung cancer shows the trend of prolonging second-line progression free survival, but does not improve the overall survival. Additionally, in the second-line treatment, chemotherapy remains an important cornerstone therapy and anti-angiogenic agent containing strategy may potentially improve survival.

## Linked entities

- **Diseases:** small cell lung cancer (MONDO:0008433)

## Full-text entities

- **Genes:** VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, TXK (TXK tyrosine kinase) [NCBI Gene 7294] {aka BTKL, PSCTK5, PTK4, RLK, TKL}, PDCD1 (programmed cell death 1) [NCBI Gene 100533201], PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, CD274 (CD274 molecule) [NCBI Gene 574058] {aka PDL1}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}
- **Diseases:** NSCLC (MESH:D002289), clear-cell renal-cell carcinoma (MESH:D002292), vomiting (MESH:D014839), brain metastases (MESH:D001932), Hepatocellular carcinoma (MESH:D006528), fatigue (MESH:D005221), pneumonia (MESH:D011014), diarrhea (MESH:D003967), Pleural effusion (MESH:D010996), hypoxic (MESH:D002534), nausea (MESH:D009325), toxicity (MESH:D064420), neuroendocrine carcinoma (MESH:D018278), irAEs (MESH:D002318), Lung Cancer (MESH:D008175), Cancer (MESH:D009369), diabetes (MESH:D003920), extensive-stage disease (MESH:D007676), death (MESH:D003643), ES-SCLC (MESH:D055752), neutropenia (MESH:D009503), hypertension (MESH:D006973), coronary heart disease (MESH:D003327), anemia (MESH:D000740), BoM (MESH:D009362)
- **Chemicals:** bevacizumab (MESH:D000068258), tremelimumab (MESH:C520704), Anlotinib (MESH:C000625192), ipilimumab (MESH:D000074324), gemcitabine (MESH:D000093542), nivolumab (MESH:D000077594), topotecan (MESH:D019772), atezolizumab (MESH:C000594389), durvalumab (MESH:C000613593), tislelizumab (MESH:C000707970), envafolimab (MESH:C000718749), etoposide (MESH:D005047), toripalimab (MESH:C000656314), temozolomide (MESH:D000077204), cemiplimab (MESH:C000627974), Irinotecan (MESH:D000077146), pembrolizumab (MESH:C582435), paclitaxel (MESH:D017239), carboplatin (MESH:D016190), Checkmate 025 (-), platinum (MESH:D010984), cisplatin (MESH:D002945), lurbinectedin (MESH:C568606)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12920424/full.md

## References

50 references — full list in the complete paper: https://tomesphere.com/paper/PMC12920424/full.md

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Source: https://tomesphere.com/paper/PMC12920424