Abstract
Purpose
Although immune-checkpoint inhibitors (ICIs) have emerged as therapeutic options for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M-HNSCC), concerns have been raised on exceptional acceleration of tumor growth during treatment with ICIs, a condition described as hyperprogressive disease (HPD). This study examined the incidence, potential predictors, and clinical impact of HPD in R/M-HNSCC.
Methods
We retrospectively collected data of patients with R/M-HNSCC treated with ICIs between January 2013 and June 2018 from 11 medical centers in Korea. HPD was defined as tumor growth kinetics ratio (TGKr) > 2, which was calculated by comparing TGK on ICIs with that before treatment with ICIs.
Results
Of 125 patients, 68 (54.4%) obtained progressive disease as their best responses (progressors). HPD was identified in 18 (26.5% of progressors, 14.4% of total) patients. Relatively younger age, primary tumor of oral cavity, and previous locoregional irradiation were significant predictors of HPD according to multivariable analysis (p = 0.040, 0.027, and 0.015, respectively). Compared to patients without HPD, patients with HPD had significantly shorter median progression-free survival (PFS) (1.2 vs. 3.4 months, p < 0.001) and overall survival (OS) (3.4 vs. 10.7 months, p = 0.047). However, interestingly, HPD did not significantly affect the therapeutic benefit of post-ICIs chemotherapy.
Conclusions
Younger patients with oral cavity cancer or prior treatment with locoregional radiotherapy could be regarded potential risk groups for HPD in patients with R/M-HNSCC treated with ICIs. Although HPD could consistently predict poorer survival outcomes, patients who experienced HPD with ICIs should not be excluded from the subsequent salvage chemotherapy treatments.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Change history
27 August 2020
In the original article published, the first name of the author is incorrect. The correct author name is Ji Hyun Park.
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Acknowledgements
This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (HA16C0015). We would like to thank Editage (www.editage.co.kr) for English language editing.
Funding
This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (HA16C0015).
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YGL, IGH, HC, and SHC provided a core assistance in data collection and developing a raw registry, which was thoroughly guided by BK, and IGH. JHP reviewed the literature, and executed the analysis of data, and mainly drafted the article with SHC. BK initially inspired and motivated the concept of present study, and along with SBK finally reviewed, and confirmed the final version of the manuscript. All co-authors listed equally contributed to enrollment of patients as expert medical oncologists of head and neck cancer, and all of them approved the final manuscript.
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This study was conducted in full accordance with the guidelines for the Good Clinical Practice and the 1964 Declaration of Helsinki. The study protocol was reviewed and approved by the institutional review board (of each participant center).
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Informed consents were achieved from all individual participants included in this study.
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Park, J.H., Chun, S.H., Lee, YG. et al. Hyperprogressive disease and its clinical impact in patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with immune-checkpoint inhibitors: Korean cancer study group HN 18–12. J Cancer Res Clin Oncol 146, 3359–3369 (2020). https://doi.org/10.1007/s00432-020-03316-5
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DOI: https://doi.org/10.1007/s00432-020-03316-5