Gino K In1,2,3, Poorva Vaidya4, Alexandra Filkins4, David J Hermel5, Kevin G King6, Omar Ragab7, William W Tseng8, Mark Swanson9, Niels Kokot9, Julie E Lang8, Lawrence Menendez10, Brittney DeClerck11,12, Gene Kim11,12, Jenny C Hu11, Alicia Terando8, Hossein Jadvar6, Charité Ricker13, Kimberly A Miller11,14, David H Peng11, Ashley Wysong15. 1. USC Norris Comprehensive Cancer Center, 1441 Eastlake Ave, NTT 3449, Los Angeles, CA, 90033, USA. gino.in@med.usc.edu. 2. Department of Dermatology, USC Keck School of Medicine, Los Angeles, CA, USA. gino.in@med.usc.edu. 3. Department of Medicine, USC Keck School of Medicine, Los Angeles, CA, USA. gino.in@med.usc.edu. 4. Department of Medicine, USC Keck School of Medicine, Los Angeles, CA, USA. 5. Division of Hematology/Oncology, Scripps Clinic, La Jolla, CA, USA. 6. Department of Radiology, USC Keck School of Medicine, Los Angeles, CA, USA. 7. Department of Radiation Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA. 8. Department of Surgery, Division of Breast, Endocrine and Soft Tissue Surgery, USC Keck School of Medicine, Los Angeles, CA, USA. 9. Caruso Department of Otolaryngology-Head and Neck Surgery, USC Keck School of Medicine, Los Angeles, CA, USA. 10. Department of Orthopaedic Surgery, USC Keck School of Medicine, Los Angeles, CA, USA. 11. Department of Dermatology, USC Keck School of Medicine, Los Angeles, CA, USA. 12. Department of Pathology, USC Keck School of Medicine, Los Angeles, CA, USA. 13. USC Norris Comprehensive Cancer Center, 1441 Eastlake Ave, NTT 3449, Los Angeles, CA, 90033, USA. 14. Department of Preventive Medicine, USC Keck School of Medicine, Los Angeles, CA, USA. 15. Department of Dermatology, University of Nebraska Medical Center, Omaha, NE, USA.
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.
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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