First-line programmed death-1 inhibitor treatment for locoregionally advanced or metastatic cutaneous squamous cell carcinoma – A real-world experience from Israel

Frontiers in Oncology

Oncology

Gal Markel¹  Eyal Fenig¹  Itamar Averbuch¹  Assaf Moore¹  Daniel Hendler¹  Noga Kurman¹  Noa Shtamper¹  Inbar Finkel¹  Tarek Taha²  Ilana Doweck³  Aron Popovtzer⁴  Kamel Mhameed⁵  Saeed Salman⁶  Salem Billan⁶ 

[1] Davidoff Cancer Center, Rabin Medical Center – Beilinson Hospital, Petach Tikva Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;Oncology Institute, Baruch Padeh Medical Center, Poriya, Affiliated with Azrieli Faculty of Medicine, Bar Ilan University, Poriya, Israel;Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel;Department of Otolaryngology-Head and Neck Surgery, Carmel Medical Center, Haifa, Affiliated to the Rappaport Faculty of Medicine, Israel Institute of Technology-Technion, Haifa, Israel;Sharett Institute of Oncology, Hadassah Medical Center, Jerusalem, Affiliated with the Hebrew University of Jerusalem, Jerusalem, Israel;The Joseph Fishman Oncology Center, Rambam Health Care Campus, Haifa, Affiliated to the Rappaport Faculty of Medicine, Israel Institute of Technology-Technion, Haifa, Israel;The Joseph Fishman Oncology Center, Rambam Health Care Campus, Haifa, Affiliated to the Rappaport Faculty of Medicine, Israel Institute of Technology-Technion, Haifa, Israel;Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel;

关键词: PD-1 inhibitor;    cemiplimab;    pembrolizumab;    radiotherapy;    cutaneous squamous cell carcinoma (cSCC);    real-world experience;   

DOI  :  10.3389/fonc.2023.1117804

 received in 2022-12-06, accepted in 2023-01-05,  发布年份 2023

来源: Frontiers

【 摘 要 】

ObjectiveCutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer worldwide. It is usually treated surgically, with very high cure rates. However, in 3%-7% of cases, cSCC metastasizes to lymph nodes or distant organs. Many of the affected patients are elderly with comorbidities who are not candidates for standard-of-care curative-intent treatment with surgery and/or radio-/chemotherapy. Immune checkpoint inhibitors, which target programmed cell death protein 1 (PD-1) pathways, have recently emerged as a potent therapeutic option. The present report presents the Israeli experience with PD-1 inhibitors for the treatment of loco-regionally advanced or metastatic cSCC in a diverse and elderly population, with or without the addition of radiotherapy.Material and methodsThe databases of two university medical centers were retrospectively searched for patients with cSCC treated with the PD-1 inhibitors cemiplimab or pembrolizumab between January 2019 and May 2022. Data on baseline, disease-related, treatment-related, and outcome parameters were collected and analyzed.ResultsThe cohort included 102 patients of a median age 78.5 years. Evaluable response data were available for 93. The overall response rate was 80.6%: complete response in 42 patients (45.2%) and partial response in 33 (35.5%). Stable disease was recorded in 7 (7.5%) and progressive disease in 11 (11.8%). Median progression-free survival was 29.5 months. Radiotherapy was administered to the target lesion during PD-1 treatment in 22.5% of patients. mPFS was not significantly different in patients who treated with RT than patients how did not (NR vs 18.4 months, HR=0.93, 95%CI: 0.39 - 2.17, p<0.859). Any-grade toxicity was recorded in 57 patients (55%), including grade ‗3 in 25, of whom 5 (5% of cohort) died. Compared to toxicity-free patients, patients with drug toxicity had better progression-free survival (18.4 months vs not reached, HR=0.33, 95% CI: 0.13-0.82, p=0.012) and higher overall response rate (87% vs 71.8%, p=0.06).ConclusionThis retrospective real-world study showed that PD-1 inhibitors were effective in the treatment of locally advanced or metastatic cSCC and appeared to be amenable for use in elderly or fragile patients with comorbidities. However, the high toxicity warrants consideration against other modalities. Induction or consolidation radiotherapy may improve the results. These findings need to be corroborated in a prospective trial.

【 授权许可】

Unknown   
Copyright © 2023 Averbuch, Salman, Shtamper, Doweck, Popovtzer, Markel, Hendler, Finkel, Moore, Fenig, Taha, Mhameed, Kurman and Billan