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The impact of combined PD-L1 positive score on clinical response to nivolumab in patients with advanced esophageal squamous cell carcinoma

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Abstract

Background

Nivolumab is recommended for patients with advanced esophageal squamous cell carcinoma (aESCC) refractory or intolerant to fluoropyrimidine- and platinum-based chemotherapy regardless of the tumor proportion score (TPS). However, the role of combined positive score (CPS) in predicting nivolumab efficacy remains unclear. We aimed to study whether TPS or CPS is a more suitable biomarker for predicting nivolumab efficacy in these patients.

Methods

We retrospectively collected data from patients with aESCC treated with fluoropyrimidines and platinum and subsequently received nivolumab monotherapy between January 1, 2014 and September 15, 2020. Next, we evaluated the efficiencies of TPS and CPS in predicting the clinical response to nivolumab using PD-L1 IHC 22C3 pharmDx assay.

Results

This study included 50 patients (CPS groups: ≥ 10/1–10/ < 1, n = 24/18/8, respectively; TPS groups, ≥ 10%/1%–10%/ < 1%, n = 17/8/25, respectively). The median progression-free survival was 3.2, 2.5, and 1.5 months in the ≥ 10, 1–10 [hazard ratio (HR) vs. CPS of ≥ 10 group, 1.01; p = 0.98; adjusted HR, 1.33; p = 0.56], and < 1 CPS groups (HR vs. CPS of ≥ 10 group, 3.44; p = 0.006; adjusted HR, 1.67; p = 0.41), respectively. For the patients with CPS of ≥ 10/1–10/ < 1 and TPS of ≥ 10%/1%–10%/ < 1%, the objective response rate was 30%/25%/0% and 36%/0%/19% and the disease control rate was 60%/50%/12% (p = 0.06) and 65%/40%/38% (p = 0.30), respectively.

Conclusions

This study suggests that a CPS of < 1 is not a strong predictor of efficacy but can predict the absence of response to nivolumab in patients with aESCC.

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Data availability

All data and materials used/generated for this study are available on request from the corresponding author.

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Acknowledgements

The authors would like to thank Enago (www.enago.jp) for the English language review.

Funding

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

Author information

Author notes

  1. Yuki Matsubara and Kazuhiro Toriyama have contributed equally to the work and are joint first authors.

Authors and Affiliations

  1. Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Yuki Matsubara, Shigenori Kadowaki, Takatsugu Ogata, Taiko Nakazawa, Kyoko Kato, Kazuki Nozawa, Yukiya Narita, Kazunori Honda, Toshiki Masuishi, Hideaki Bando, Masashi Ando & Kei Muro

  2. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan

    Kazuhiro Toriyama & Waki Hosoda

  3. Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Kazuhiro Toriyama

  4. Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan

    Masahiro Tajika

  5. Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan

    Isao Oze

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  1. Yuki Matsubara
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Contributions

YM and HT conceptualized and designed the study. YM collected clinical data, drafted the manuscript, and performed the statistical analysis. HT performed the PD-L1 staining diagnosis of all tissue specimens. SK was responsible for this study and helped write the manuscript. WH performed PD-L1 staining and helped in pathological diagnosis. IO assisted in statistical analysis. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Shigenori Kadowaki.

Ethics declarations

Ethical statement and consent to participate

The institutional review board of Aichi Cancer Center Hospital, Japan, approved this study (R021076). The institutional review board also waived the requirement for informed consent because of the observational retrospective nature of this study, with an opt-out option indicated at the institution’s website.

Conflict of interest

YM received an honorarium from Takeda, Merck BioPharma, and Taiho. SK received an honorarium from Eli Lilly, Taiho, Ono, Bristol-Myers Squibb, Chugai, Bayer, Merck Serono, Daiichi Sankyo, and Esai as well as research funding from Taiho, Eli Lilly, MSD, Chugai, Nobelpharma, Ono, Daiichi Sankyo, and Yansen. TO received an honorarium from Ono, Bristol-Myers Squibb, Taiho, MSD, and Eli Lilly. TN received an honorarium from Eli Lilly. YN received an honorarium from Yakult Honsha, Taiho, Eli Lilly, Daiichi Sankyo, and AstraZeneca as well as research funding from Ono and Bristol-Myers Squibb. YN is also a member of the advisory board of Daiichi Sankyo. TM received an honorarium from Takeda, Chudai, Merck BioPharma, Taiho, Bayer, Eli Lilly, Yakult Honsha, Sanofi, Daiichi Sankyo, Ono, and Bristol-Myers Squibb as well as research funding from MSD, Daiichi Sankyo, Ono, and Novartis. HB received an honorarium from Ono, Eli Lilly, and Taiho as well as research funding from Ono. MT received an honorarium from EA Pharma, Otsuka Pharmaceutical Factory, and Bristol-Myers Squibb. KM received an honorarium from Ono, Chugai, Takeda, Taiho, Sanofi, Bristol-Myers Squibb, Eli Lilly, and Bayer; research funding from Solasia Pharma, Merck Serono, Daiichi Sankyo, Parexel International, Pfizer, MSD, Amgen, ONO, Astellas, Sanofi, Taiho, and Esai; and consulting fees from AstraZeneca, Ono, and Amgen. KM is also a member of the advisory boards of Ono, MSD, AstraZeneca, Daiichi Sankyo, and Solasia Pharma.

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All data and materials used for this study are available on request.

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Supplementary Information

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Supplementary file1 (DOCX 26 KB)

10388_2022_978_MOESM2_ESM.docx

Supplementary file2 Supplementary Fig. 1 ROC curves showing the relation between CPS or TPS and the efficacy outcomes: a response, b disease control, and c disease progression. ROC receiver operating characteristic, CPS combined positive score, TPS tumor proportion score, AUC areas under the curves (DOCX 236 KB)

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Matsubara, Y., Toriyama, K., Kadowaki, S. et al. The impact of combined PD-L1 positive score on clinical response to nivolumab in patients with advanced esophageal squamous cell carcinoma. Esophagus 20, 524–532 (2023). https://doi.org/10.1007/s10388-022-00978-7

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  • DOI: https://doi.org/10.1007/s10388-022-00978-7

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