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Predictive value of p53 and AXL immunostaining for the efficacy of immune checkpoint inhibitor-based therapy after osimertinib treatment in patients with epidermal growth factor-mutant non-small cell lung cancer

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Abstract

Background

Current evidence indicates that immune checkpoint inhibitors (ICIs) have a limited efficacy in patients with lung cancer harboring epidermal growth factor receptor (EGFR) mutations. However, there is a lack of data on the efficacy of ICIs after osimertinib treatment, and the predictors of ICI efficacy are unclear.

Methods

We retrospectively assessed consecutive patients with EGFR-mutant NSCLC who received ICI-based therapy after osimertinib treatment at 10 institutions in Japan, between March 2016 and March 2021. Immunohistochemical staining was used to evaluate the expression of p53 and AXL. The deletions of exon 19 and the exon 21 L858R point mutation in EGFR were defined as common mutations; other mutations were defined as uncommon mutations.

Results

A total of 36 patients with advanced or recurrent EGFR-mutant NSCLC were analyzed. In multivariate analysis, p53 expression in tumors was an independent predictor of PFS after ICI-based therapy (p = 0.002). In patients with common EGFR mutations, high AXL expression was a predictor of shorter PFS and overall survival after ICI-based therapy (log-rank test; p = 0.04 and p = 0.02, respectively).

Conclusion

The levels of p53 in pretreatment tumors may be a predictor of ICI-based therapy outcomes in patients with EGFR-mutant NSCLC after osimertinib treatment. High levels of AXL in tumors may also be a predictor of ICI-based therapy outcomes, specifically for patients with common EGFR mutations. Further prospective large-scale investigations on the predictors of ICI efficacy following osimertinib treatment are warranted.

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Data availability

The datasets generated during the current study are not publicly available because of ethical constraints but are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors sincerely appreciate the contributions of all the physicians and patients who participated in this study.

Funding

This research was conducted without any funding.

Author information

Authors and Affiliations

  1. Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-Cho, Kamigyo-Ku, Kyoto, Japan

    Kenji Morimoto, Tadaaki Yamada, Ryo Sawada, Satomi Tanaka, Akihiro Yoshimura, Masahiro Iwasaku, Shinsaku Tokuda, Young Hak Kim & Koichi Takayama

  2. Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka City, Japan

    Koichi Azuma

  3. Department of Respiratory Medicine, Fujita Health University School of Medicine, Aichi, Japan

    Yasuhiro Goto

  4. Department of Medical Oncology, Fukuchiyama City Hospital, Kyoto, Japan

    Taishi Harada

  5. Department of Respiratory Medicine, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan

    Shinsuke Shiotsu

  6. Department of Pulmonary Medicine, Rakuwakai Otowa Hospital, Kyoto, Japan

    Nobuyo Tamiya

  7. Department of Respiratory Medicine, Uji-Tokushukai Medical Center, Kyoto, Japan

    Yusuke Chihara

  8. Department of Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan

    Takayuki Takeda

  9. Department of Pulmonary Medicine, Otsu City Hospital, Shiga, Japan

    Osamu Hiranuma

  10. Department of Pulmonary Medicine, Saiseikai Shiga Hospital, Shiga, Japan

    Isao Hasegawa

Authors
  1. Kenji Morimoto
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Contributions

TY contributed to conceptualization, methodology, formal analysis, writing—original draft preparation, writing—review and editing, and supervision. KM was involved in methodology, investigation, formal analysis, writing—original draft preparation, writing—review and editing, project administration, data curation. RS contributed to methodology. KA, YG, TH, SS, NT, YC, TT, OH, IH, and ST were involved in Investigation. KT contributed to writing—original draft preparation, writing—review and editing, supervision. AY, YHK, MI and ST was involved in project administration and data curation.

Corresponding author

Correspondence to Tadaaki Yamada.

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Conflict of interest

TY received grants from Pfizer, Ono Pharmaceutical, Janssen Pharmaceutical, and Takeda Pharmaceutical and personal fees from Eli Lilly. KA received personal fees from Ono Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, MSD Oncology, and Bristol-Myers Squibb outside the submitted work. KT received grants from Chugai Pharmaceutical and Ono Pharmaceutical and personal fees from AstraZeneca, Chugai Pharmaceutical, MSD, Eli Lilly, Boehringer Ingelheim, and Daiichi Sankyo. The other authors have no further conflicts of interest to declare.

Ethics approval

The study protocol was approved by the ethics committee of each hospital, including the Kyoto Prefectural University of Medicine (Approval no. ERB-C-1918).

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Because this was a retrospective study, the need for informed consent was waived, and an official website was used as an opt-out method.

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Morimoto, K., Yamada, T., Sawada, R. et al. Predictive value of p53 and AXL immunostaining for the efficacy of immune checkpoint inhibitor-based therapy after osimertinib treatment in patients with epidermal growth factor-mutant non-small cell lung cancer. Cancer Immunol Immunother 72, 1699–1707 (2023). https://doi.org/10.1007/s00262-023-03370-1

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