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Dissociated response and clinical benefit in patients treated with nivolumab monotherapy

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Abstract

Immune checkpoint inhibitors (ICIs) are effective for previously treated patients with advanced non-small cell lung cancer (NSCLC). However, an unconventional response pattern is sometimes encountered. A dissociated response (DR), characterized by some lesions shrinking and others growing, has been recognized with ICI treatment. In this study, we examined the characteristics and treatment outcomes of DR in previously treated NSCLC patients, receiving nivolumab monotherapy. We conducted a retrospective cohort study of previously treated patients with advanced NSCLC who received nivolumab. We assessed the tumor response of each organ using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at the first radiologic evaluation. We investigated treatment outcome and compared overall survival using the Kaplan-Meier Method and log-rank tests. Further, we conducted the same analysis in patients who had previously received chemotherapy or tyrosine kinase inhibitor therapy in our hospital. Between April 2016 and September 2018, 107 patients who received nivolumab fulfilled the inclusion criteria. Of them, 5 (5%) patients showed a DR. There were no specific differences in characteristics between DR and non-DR cases. Patients showing DR had significantly longer overall survival than those showing concordant progressive disease (46.9 vs. 8.2 months, p = 0.038). The frequencies of DR in the ICI, chemotherapy, and tyrosine kinase inhibitor-treated cohorts were 5%, 1%, and 4%, respectively. DR was uncommon, but this presented a distinctive pattern of nivolumab response. Some patients might benefit from continuing nivolumab therapy and may achieve a longer overall survival.

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Data availability

All datasets on which the conclusions of this paper rely are available on request.

Abbreviations

CR:

Complete response

DR:

Dissociated response

ECOG-PS:

Eastern Cooperative Oncology Group performance status

EGFR:

Epidermal growth factor receptor

ICI:

Immune checkpoint inhibitor

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

PD:

Progressive disease

PD-1:

Programmed death protein 1

PD-L1:

Programmed death ligand 1

PR:

Partial response

RECIST:

Response Evaluation Criteria in Solid Tumors

SD:

Stable disease

SLD:

Sum of the longest diameter

TPS:

Tumor proportion score

TKI:

Tyrosine kinase inhibitor

iUPD:

Unconfirmed progressive disease

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Acknowledgements

The authors would like to thank Keiko Sakuragawa and Kanako Masuta for her administrative assistance, and Yukihiro Imai for conducting the pathological analyses. We would like to thank Editage (www.editage.com) for English language editing.

Authors’ information

Yuki Sato: yuki1130sato@gmail.com; Takeshi Morimoto: morimoto@kuhp.kyoto-u.ac.jp; Shigeo Hara: shigeo_hara@kcho.jp; Kazutaka Hosoya: hsyn0917@gmail.com; Kazuma Nagata: knagata@kcho.jp; Atsushi Nakagawa: a.nakagawa@kcho.jp; Ryo Tachikawa: ryotkw@gmail.com; Keisuke Tomii; ktomii@kcho.jp

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. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan

    Yuki Sato, Kazuma Nagata, Kazutaka Hosoya, Atsushi Nakagawa, Ryo Tachikawa & Keisuke Tomii

  2. Department of Clinical Research Center, Kobe City Medical Center General Hospital, Kobe, 650-0047, Japan

    Takeshi Morimoto

  3. Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, 663-8501, Japan

    Takeshi Morimoto

  4. Department of Clinical Pathology, Kobe City Medical Center General Hospital, Kobe, 650-0047, Japan

    Shigeo Hara

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  1. Yuki Sato
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Correspondence to Yuki Sato.

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Ethics approval and consent to participate

This study was conducted with the approval of the Kobe City Medical Center General Hospital Ethics Committee (No. zn190108).

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Informed consent was not required owing to the retrospective nature of the study.

Competing interests

Dr. Sato has received lecture fees from Ono Pharmaceutical Co., Ltd. (Osaka, Japan). Dr. Morimoto has received manuscript preparation fees and was on an advisory board of Bristol-Myers Squibb K.K. (Tokyo, Japan). Dr. Hosoya has received lecture fees from Ono Pharmaceutical Co., Ltd. (Osaka, Japan). All remaining authors have no conflicts of interest to declare. We wish to confirm that there are no other known conflicts of interest associated with this publication. Further, there was no significant financial support for this work that could have influenced its outcome.

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Sato, Y., Morimoto, T., Hara, S. et al. Dissociated response and clinical benefit in patients treated with nivolumab monotherapy. Invest New Drugs 39, 1170–1178 (2021). https://doi.org/10.1007/s10637-021-01077-7

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