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Organ-specific response to nivolumab in patients with non-small cell lung cancer (NSCLC)

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Abstract

Background

Response to immune checkpoint inhibitors depends on tumor intrinsic properties and also on host factors in the tumour microenvironment including the presence of immune cells (IC). We hypothesized that nivolumab efficacy varies across different metastatic sites.

Methods

We retrospectively analyzed computed tomography scans of patients with metastatic non-small cell lung carcinoma (NSCLC) receiving nivolumab. RECIST 1.1 criteria were applied to assess the overall response rate (ORR) and organ-specific response rate (OSRR).

Results

We analyzed 52 patients including 44% females, 58% adenocarcinoma and 8% never smokers. Involved organs had target-lesions in the lung (42%), liver (25%), lymph nodes (56%) and soft tissue (13%) and non-target lesions in the bones (23%). ORR and disease control rate (DCR) were 20% and 45%, respectively. Median overall survival, progression-free survival and duration of response were 11.9, 2.3 and 10.3 months. OSRR and organ-specific DCR (OSDCR) were 28% and 90% in lymph nodes, 8% and 54 in the liver, and 9% and 55% in lung metastases. Nine out of 12 patients with bone metastases had progressive lesions. The cumulative incidence probability of organ-specific progression at 6 months was 14% in lymph nodes, 42% in the liver, 36% in lung metastases and 26% in the primary tumor, 29% in soft tissue and 33% in adrenal metastases.

Conclusion

In conclusion, the efficacy of immunotherapy is dependent on the metastatic location. Treatment appears more active in lymph nodes compared to other organ sites such as liver, adrenals and bone. Future strategies may include additional local treatment in case of oligoprogression in these organs in patients with otherwise sustained treatment benefit.

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Abbreviations

APC:

Antigen-presenting cells

CR:

Complete remission

CT:

Computed

DCR:

Disease control rate

NSCLC:

Non-small cell lung cancer

ORR:

Overall response rate

OS:

Overall survival

OSDCR:

Organ-specific disease control rate

OSRR:

Organ-specific response rate

PD:

Progressive disease

PD-L1:

Programmed death ligand 1

PFS:

Progression-free survival

PR:

Partial remission

SD:

Stable disease

SUV:

Standard uptake value

TME:

Tumor microenvironment

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Acknowledgements

Institutional grant was received by BMS for data collection and statistical analysis.

Author information

Author notes

  1. Sabine Schmid and Stefan Diem contributed equally as first authors.

Authors and Affiliations

  1. Department of Oncology and Haematology, Cantonal Hospital St. Gallen, Rorschacherstrasse 95, 9007, St. Gallen, Switzerland

    Sabine Schmid, Stefan Diem & Martin Früh

  2. SAKK, Swiss Group for Clinical Cancer Research, Bern, Switzerland

    Qiyu Li & Dirk Klingbiel

  3. University of Bern, Bern, Switzerland

    Sabine Schmid, Mirjam Krapf & Martin Früh

  4. Department of Immunbiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

    Stefan Diem & Lukas Flatz

  5. Department of Radiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

    Sebastian Leschka & Lotus Desbiolles

  6. Institute of Pathology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

    Wolfram Jochum

  7. Department of Oncology/Haematology, Spital Grabs, Grabs, Switzerland

    Stefan Diem

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  1. Sabine Schmid
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Contributions

Conception and design: SS, SD, MF. Collection and assembly of data: SS, SD, MK. Data analysis and interpretation. Radiology: LD, SL. Statistics: DK, QL. Overall Interpretation: SS, SD, MF. Manuscript writing: all authors. Final approval of manuscript: all authors.

Corresponding author

Correspondence to Sabine Schmid.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required. This article does not contain any studies with animals performed by any of the authors. The study was approved by the local Research Ethics Committee (Ethikkommission Ostschweiz-EKOS).

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Schmid, S., Diem, S., Li, Q. et al. Organ-specific response to nivolumab in patients with non-small cell lung cancer (NSCLC). Cancer Immunol Immunother 67, 1825–1832 (2018). https://doi.org/10.1007/s00262-018-2239-4

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  • DOI: https://doi.org/10.1007/s00262-018-2239-4

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