ANTI-PD-1 FOR THE TREATMENT OF ADVANCED CUTANEOUS SQUAMOUS CELL CARCINOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS



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Abstract

Background: Advanced cutaneous squamous cell carcinoma (CSCC) is a formidable cancer with historically constrained systemic therapy alternatives. Immune checkpoint drugs that target programmed cell death-1 (PD-1) and programmed death ligand-1 (PD-L1) have surfaced as viable treatments. This revised systematic review and meta-analysis sought to assess the effectiveness of anti-PD-1/PD-L1–based therapy in advanced CSCC.

Methods: A thorough search of PubMed, Scopus, and Web of Science was performed till August 12, 2025. Eligible studies comprised clinical trials and observational cohorts that reported the objective response rate (ORR) in patients with advanced CSCC treated with anti-PD-1/PD-L1 drugs. Pooled estimates were derived utilizing a random-effects model with limited maximum likelihood (REML) estimation. Heterogeneity was evaluated using Cochran’s Q, I², and τ². Subgroup analyses were conducted based on drug regimen, geographic location, and study design. Publication bias was assessed by funnel plots and Egger’s regression analysis.

Results: Forty-eight studies involving 4,172 patients met the inclusion criteria. The pooled ORR was 0.51 (95% CI, 0.46–0.55; z = 21.21, p < 0.001) with substantial heterogeneity (I² = 89.13%). Subgroup analyses showed ORRs ranging from 0.21 to 0.73 by drug regimen, with cemiplimab plus pembrolizumab achieving the highest response rates. Geographic location (p = 0.014, R² = 14.52%) and study design (p = 0.002, R² = 16.84%) were significantly associated with treatment effect, while drug type alone was not (p = 0.679). Egger’s test indicated small-study effects (p = 0.0174).

Conclusion: Anti-PD-1/PD-L1 therapy demonstrates meaningful clinical activity in advanced CSCC, achieving responses in approximately half of treated patients. Geographic and methodological factors contribute to outcome variability, underscoring the need for large, biomarker-driven trials to refine patient selection and optimize therapeutic benefit.

Об авторах

Ameneh Hashemzehi

Islamic Azad University, Kazeroon, Iran

Email: Hashemzehiameneh@gmail.com

Faculty of veterinary medicine, Islamic Azad University, Kazeroon, Iran.

Иран

Fatemeh Shirali

Ahvaz Jondi Shapour University of Medical Sciences, Ahvaz, Iran

Email: Fatishirali12345@gmail.com

School of Medicine, Ahvaz Jondi Shapour University of Medical Sciences, Ahvaz, Iran.

Иран

Hanieh Norooziseyedhosseini

I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation

Email: H1996norozi@gmail.com

I.M. Sechenov First Moscow State Medical University, 8-2 Trubetskaya Street, Moscow 119991, Russian Federation.

Россия

Roya Imani

I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation

Email: roz_im74@yahoo.com

I.M. Sechenov First Moscow State Medical University, 8-2 Trubetskaya Street, Moscow 119991, Russian Federation.

Россия

Dorsa Sadat Shahrava

Roudehen Branch, Islamic Azad University, Roudehen, Iran

Email: dorsashahrava@gmail.com

Department of Biology, Faculty of Basic sciences, Roudehen Branch, Islamic Azad University, Roudehen, Iran.

Иран

Javad Nadem

Guilan University of Medical Sciences, Rasht, Iran

Email: javad.n.c@gmail.com

School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.

Иран

Faezeh Hoseinpour

Islamic Azad University, Kazeroon, Iran

Email: Niloofar.deravi@hotmail.com

Islamic Azad University of Medical Science Qeshm International Branch, Qeshm, Iran.

Иран

Javad Hataminia

Hormozgan University of Medical Sciences, Bandar Abbas, Iran

Email: hataminiajavad@gmail.com

Student Research Committee, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

Иран

Omid Salimi

Islamic Azad University, Kazeroon, Iran

Email: salimiomid953@gmail.com

Department of Medicine, Na.C., Islamic Azad University, Najafabad, Iran.

Student research committee, Na.C., Islamic Azad University, Najafabad, Iran

Иран

Alireza Amini

Islamic Azad University, Kazeroon, Iran

Email: alirezaamini031k@gmail.com

Department of Medicine, Na.C., Islamic Azad University, Najafabad, Iran. Student research committee, Na.C., Islamic Azad University, Najafabad, Iran

Иран

Amirali Ghorbani Sharif

Islamic Azad University, Kazeroon, Iran

Email: aghorbanisharif@gmail.com

Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Иран

Sepideh Hadimaleki

Tabriz University of Medical Sciences, Tabriz, Iran

Email: sepidhadi74@gmail.com

Department of Pathology, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.

Иран

Benyamin Rahimi

Tabriz University of Medical Sciences, Tabriz, Iran

Email: rahimi_benyamin@yahoo.com

Department of Urology, Imam Reza Hospital, Tabriz University of Medical Science, Tabriz, Iran.

Иран

Mahdyieh Naziri

Iran University of Medical Sciences, Tehran, Iran

Email: nazirimahdyieh@yahoo.com

Students Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Иран

Niloofar Deravi

Shahid Beheshti University of Medical Sciences, Tehran, Iran

Email: niloofar.deravi@gmail.com

Students Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Иран

Parisa Mehrasa

Tabriz University of Medical Sciences, Tabriz, Iran

Автор, ответственный за переписку.
Email: Parisamehrasa@yahoo.com

Assistant Professor of Pathology, Department of Pathology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

Иран

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