Clinical outcomes following PD-1 inhibitor elective discontinuation in cutaneous squamous cell carcinoma: exploring treatment de-escalation
Abstract Background Non-melanoma skin cancers (NMSC) are the most common malignancies worldwide. While early-stage lesions can be definitively treated with local therapies, advanced stage cutaneous squamous cell carcinoma (cSCC) often requires systemic treatments such as PD-1 inhibitors. These treat...
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Springer
2025-07-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-025-04115-y |
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| author | Itamar Averbuch Nofar Edri Nethanel Asher Gal Markel Daniel Hendler Hadas Ditzian Kugler Eyal Yosefof Noga Kurman |
| author_facet | Itamar Averbuch Nofar Edri Nethanel Asher Gal Markel Daniel Hendler Hadas Ditzian Kugler Eyal Yosefof Noga Kurman |
| author_sort | Itamar Averbuch |
| collection | DOAJ |
| description | Abstract Background Non-melanoma skin cancers (NMSC) are the most common malignancies worldwide. While early-stage lesions can be definitively treated with local therapies, advanced stage cutaneous squamous cell carcinoma (cSCC) often requires systemic treatments such as PD-1 inhibitors. These treatments may be administered for prolonged durations; this practice may lead to an unnecessary physical and financial toxicity. The purpose of this study was to evaluate the patterns of disease progression after anti-PD-1 therapy discontinuation in this group of patients. Methods This retrospective cohort study included patients diagnosed with advanced cSCC and treated with either cemiplimab or pembrolizumab from 2019 to 2024 at a single university-affiliated tertiary medical center. Results The cohort included 131 patients, with a 73% overall response rate. Among the 86 patients with either partial or complete response as the best response included in the final analysis, 40 (47%) patients had a treatment break for at least 3 months, and 46 (53%) continued without discontinuation to a maximal duration of 2 years. After a median follow-up of 29.9 months, 24 (60%) patients in the break group remained progression-free, systemic treatment-free, and alive throughout the follow-up. Four patients (10%) experienced disease progression. Among these, the best overall response was PR in three patients and CR in one patient. Nine (22.5%) patients died due to non-oncological reasons, two (5%) patients died from an unknown cause, and one (2.5%) due to treatment toxicity. The percentage of patients achieving CR was statistically significantly higher in the break group compared to the no-break group. Conclusions Our findings advocate for a more tailored approach to the duration of PD-1 inhibitor therapy in cSCC, potentially reducing burdens of overtreatment. Future studies regarding establishing robust predictors for safe treatment discontinuation are required to enhance decision-making in clinical practice. |
| format | Article |
| id | doaj-art-f4384a64f5e34e249f12988e1630a080 |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-f4384a64f5e34e249f12988e1630a0802025-08-20T03:46:08ZengSpringerCancer Immunology, Immunotherapy1432-08512025-07-017481710.1007/s00262-025-04115-yClinical outcomes following PD-1 inhibitor elective discontinuation in cutaneous squamous cell carcinoma: exploring treatment de-escalationItamar Averbuch0Nofar Edri1Nethanel Asher2Gal Markel3Daniel Hendler4Hadas Ditzian Kugler5Eyal Yosefof6Noga Kurman7Davidoff Cancer Center, Rabin Medical Center – Beilinson HospitalDavidoff Cancer Center, Rabin Medical Center – Beilinson HospitalDavidoff Cancer Center, Rabin Medical Center – Beilinson HospitalDavidoff Cancer Center, Rabin Medical Center – Beilinson HospitalDavidoff Cancer Center, Rabin Medical Center – Beilinson HospitalDavidoff Cancer Center, Rabin Medical Center – Beilinson HospitalDavidoff Cancer Center, Rabin Medical Center – Beilinson HospitalDavidoff Cancer Center, Rabin Medical Center – Beilinson HospitalAbstract Background Non-melanoma skin cancers (NMSC) are the most common malignancies worldwide. While early-stage lesions can be definitively treated with local therapies, advanced stage cutaneous squamous cell carcinoma (cSCC) often requires systemic treatments such as PD-1 inhibitors. These treatments may be administered for prolonged durations; this practice may lead to an unnecessary physical and financial toxicity. The purpose of this study was to evaluate the patterns of disease progression after anti-PD-1 therapy discontinuation in this group of patients. Methods This retrospective cohort study included patients diagnosed with advanced cSCC and treated with either cemiplimab or pembrolizumab from 2019 to 2024 at a single university-affiliated tertiary medical center. Results The cohort included 131 patients, with a 73% overall response rate. Among the 86 patients with either partial or complete response as the best response included in the final analysis, 40 (47%) patients had a treatment break for at least 3 months, and 46 (53%) continued without discontinuation to a maximal duration of 2 years. After a median follow-up of 29.9 months, 24 (60%) patients in the break group remained progression-free, systemic treatment-free, and alive throughout the follow-up. Four patients (10%) experienced disease progression. Among these, the best overall response was PR in three patients and CR in one patient. Nine (22.5%) patients died due to non-oncological reasons, two (5%) patients died from an unknown cause, and one (2.5%) due to treatment toxicity. The percentage of patients achieving CR was statistically significantly higher in the break group compared to the no-break group. Conclusions Our findings advocate for a more tailored approach to the duration of PD-1 inhibitor therapy in cSCC, potentially reducing burdens of overtreatment. Future studies regarding establishing robust predictors for safe treatment discontinuation are required to enhance decision-making in clinical practice.https://doi.org/10.1007/s00262-025-04115-yCutaneous squamous cell carcinomaPD-1 inhibitorsAnti-PD-1 therapy discontinuation |
| spellingShingle | Itamar Averbuch Nofar Edri Nethanel Asher Gal Markel Daniel Hendler Hadas Ditzian Kugler Eyal Yosefof Noga Kurman Clinical outcomes following PD-1 inhibitor elective discontinuation in cutaneous squamous cell carcinoma: exploring treatment de-escalation Cancer Immunology, Immunotherapy Cutaneous squamous cell carcinoma PD-1 inhibitors Anti-PD-1 therapy discontinuation |
| title | Clinical outcomes following PD-1 inhibitor elective discontinuation in cutaneous squamous cell carcinoma: exploring treatment de-escalation |
| title_full | Clinical outcomes following PD-1 inhibitor elective discontinuation in cutaneous squamous cell carcinoma: exploring treatment de-escalation |
| title_fullStr | Clinical outcomes following PD-1 inhibitor elective discontinuation in cutaneous squamous cell carcinoma: exploring treatment de-escalation |
| title_full_unstemmed | Clinical outcomes following PD-1 inhibitor elective discontinuation in cutaneous squamous cell carcinoma: exploring treatment de-escalation |
| title_short | Clinical outcomes following PD-1 inhibitor elective discontinuation in cutaneous squamous cell carcinoma: exploring treatment de-escalation |
| title_sort | clinical outcomes following pd 1 inhibitor elective discontinuation in cutaneous squamous cell carcinoma exploring treatment de escalation |
| topic | Cutaneous squamous cell carcinoma PD-1 inhibitors Anti-PD-1 therapy discontinuation |
| url | https://doi.org/10.1007/s00262-025-04115-y |
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