Abstract
Purpose
Approximately 5% of patients with cutaneous squamous cell carcinoma (CSCC) may develop recurrent or metastatic disease. The management of such cases is challenging and requires multi-disciplinary care. Immunotherapy using PD-1 inhibition was approved to treat unresectable or metastatic CSCC in 2018. Given limited data regarding clinical outcomes outside of published trials, we describe our experience using this therapy.
Methods
We retrospectively reviewed all patients treated with PD-1 inhibition as therapy for locally advanced, regionally metastatic or distant metastatic CSCC at the University of Southern California. Clinicopathological characteristics, treatment data using PD-1 inhibitors, and outcomes were assessed.
Results
Among 26 patients treated with PD-1 inhibition, the objective response rate was 42.3%, with 19.2% of patients having partial response and 23.1% having complete response to therapy. The median progression-free survival was 5.4 months. Median tumor mutational burden (TMB) was higher among responders compared to non-responders (60 vs. 9 Mut/Mb, p = 0.04). Primary CSCC tumor location on the head/neck was also associated with response to PD-1 inhibition (p = 0.04). Two patients with mutations affecting mismatch repair deficiency were noted to have complete response to treatment. No other variables were associated with treatment outcomes.
Conclusion
PD-1 inhibition produces durable responses among patients with advanced or metastatic CSCC. PD-1 inhibition therapy is well tolerated, but patients should be monitored closely for immune-related adverse events, particularly frail or immune-suppressed patients. Further investigation of potential biomarkers to help identify patients who will derive the most benefit from this therapeutic option is needed.
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Acknowledgements
The authors would like to thank all the patients and their loved ones; without them, this work would not have been possible. We also acknowledge all researchers, clinicians and organizations working in this field for their contributions and dedication, and we humbly apologize to those whose work we did not report or cite.
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GKI, PV, AF, and DJH: conception and design; acquisition, analysis and interpretation of data; drafting and revision. KGK, OR, WWT, MS, NK, JEL, LM, BD, GK, JCH, AT, HJ, CR, KAM, DHP, and AW: acquisition, analysis and interpretation of data; drafting and revision. All the authors approved the version to be published, and agree to be accountable for all aspects of the work.
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Gino K. In: advisory boards/consulting for Sanofi, BMS, Novartis, Array, and Castle Biosciences; speaker for Merck; clinical trials/research support from Genentech, Idera, and Regeneron. Julie E. Lang: speaker for Genomic Health; research support from ANGLE Parsortix. Jenny C. HU: advisory board for Regeneron. Ashley Wysong: research support from Castle Biosciences. All the other authors: no conflicts.
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This study was reviewed and approved by the institutional review board at the University of Southern California. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. All data and materials support the published claims and comply with field standards. This work has been partially presented in abstract form at the 2018 ASCO Annual Meeting. Otherwise, all the other content has not been published elsewhere, nor is under consideration for publication anywhere else.
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In, G.K., Vaidya, P., Filkins, A. et al. PD-1 inhibition therapy for advanced cutaneous squamous cell carcinoma: a retrospective analysis from the University of Southern California. J Cancer Res Clin Oncol 147, 1803–1811 (2021). https://doi.org/10.1007/s00432-020-03458-6
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DOI: https://doi.org/10.1007/s00432-020-03458-6