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Efficacy and safety of atezolizumab, in combination with etoposide and carboplatin regimen, in the first-line treatment of extensive-stage small-cell lung cancer: a single-center experience

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Background

Patients with small-cell lung cancer (SCLC) have a dismal prognosis with limited overall survival (OS) despite a high response rate to chemotherapy. Recently, immune checkpoint inhibitors, combined with chemotherapy, as the first-line treatment for extensive-stage (ES)-SCLC have shown improvement in clinical outcomes.

Patients and methods

Real-world data from 68 Korean ES-SCLC patients, treated with atezolizumab, etoposide, and carboplatin at Yonsei Cancer Center between June 2019 and November 2020, were retrospectively analyzed to determine safety and efficacy using Cox regression analysis.

Results

The median follow-up was 11.6 months. The median progression-free survival was 4.6 months (95% confidence interval [CI] 4.0–5.2), and the median OS was 12.0 months (95% CI 7.4–16.6). Baseline bone metastasis, immune-related adverse events (IRAEs), and elevated LDH were related to OS (hazard ratio 2.18, 0.33, and 4.64; P = 0.05, 0.02, and 0.003, respectively). Among the 42 patients with disease progression, liver metastasis progression and baseline bone metastasis were associated with inferior OS, but without statistical significance (hazard ratio 2.47 and 1.97; P = 0.25 and 0.26, respectively). Overall, 61 (89.7%) patients experienced treatment-related adverse events (TRAEs), with hematologic toxicities as the most common grade 3–4 TRAEs. Twenty-two (32.4%) patients experienced IRAEs, with skin rash as the most common, and five (7.4%) patients had grade-3 IRAEs (pneumonitis, hyperglycemia, and aspartate aminotransferase elevation).

Conclusion

Atezolizumab, combined with etoposide and carboplatin, showed efficacy and safety in our real-world data. Further studies are needed to predict the response to immunotherapy in SCLC.

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Data Availability

All data generated or analyzed during this study are included in this published article (and its supplementary information files).

Code availability

Not applicable.

Abbreviations

CRT:

Concurrent chemoradiation therapy

CI:

Confidence interval

CR:

Complete response

ES-SCLC:

Extensive-stage small-cell lung cancer

HR:

Hazard ratio

ICI:

Immune checkpoint inhibitor

IRAE:

Immune-related adverse event

mPFS:

Median progression-free survival

mOS:

Median overall survival

NSCLC:

Non-small cell lung cancer

ORR:

Objective response rate

OS:

Overall survival

PD-1:

Programmed death protein-1

PD-L1:

Programmed death-ligand 1

PFS:

Progression-free survival

PR:

Partial response

RECIST:

Response Evaluation Criteria in Solid Tumors

SCLC:

Small-cell lung cancer

TRAE:

Treatment-related adverse event

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Acknowledgements

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Division of Medical Oncology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

    Seoyoung Lee

  2. Department of Pathology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea

    Hyo Sup Shim

  3. Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Yonsei-ro 50-1, Seodaemun-gu, Seoul, 03722, Korea

    Beung-Chul Ahn, Sun Min Lim, Hye Ryun Kim, Byoung Chul Cho & Min Hee Hong

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Contributions

SL and MHH conceptualized and designed the study. SL, HSS, BCA, SML, HRK, BCC, and MHH were involved in data acquisition. SL and MHH analyzed and interpreted data. SL performed statistical analysis. The first draft of the manuscript was written by SL and MHH, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Min Hee Hong.

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The authors have no conflicts of interest to declare that are relevant to the content of this article.

Ethics approval

The study was approved by the institutional review board (IRB) at Severance Hospital (IRB number 4–2020-1151), and all experiments were performed in accordance with the guidelines and regulations of IRB of Severance Hospital. This study was given a formal waiver for the need of consent by the institutional review board of Severance Hospital in view of the retrospective nature of the study.

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The study provides real-world data of Korean small-cell lung cancer patients showing comparable outcomes with IMpower133 study, in which Asians were underrepresented. Bone metastasis and liver metastasis progression suggested a poor prognosis.

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Lee, S., Shim, H.S., Ahn, BC. et al. Efficacy and safety of atezolizumab, in combination with etoposide and carboplatin regimen, in the first-line treatment of extensive-stage small-cell lung cancer: a single-center experience. Cancer Immunol Immunother 71, 1093–1101 (2022). https://doi.org/10.1007/s00262-021-03052-w

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