Immune Checkpoint Inhibitors to Treat Cutaneous Malignancies

Overview

Journal J Am Acad Dermatol

Specialty Dermatology

Date 2020 May 29

PMID 32461079

Citations 42

Authors

Dulce M Barrios

Mytrang H Do

Gregory S Phillips

Michael A Postow

Tomoko Akaike

Paul Nghiem

Mario E Lacouture

Affiliations

Soon will be listed here.

Abstract

As the incidence of cutaneous malignancies continues to rise and their treatment with immunotherapy expands, dermatologists and their patients are more likely to encounter immune checkpoint inhibitors. While the blockade of immune checkpoint target proteins (cytotoxic T-lymphocyte-associated protein-4, programmed cell death-1, and programmed cell death ligand-1) generates an antitumor response in a substantial fraction of patients, there is a critical need for reliable predictive biomarkers and approaches to address refractory disease. The first article of this Continuing Medical Education series reviews the indications, efficacy, safety profile, and evidence supporting checkpoint inhibition as therapeutics for metastatic melanoma, cutaneous squamous cell carcinoma, and Merkel cell carcinoma. Pivotal studies resulting in the approval of ipilimumab, pembrolizumab, nivolumab, cemiplimab, and avelumab by regulatory agencies for various cutaneous malignancies, as well as ongoing clinical research trials, are discussed.

Citing Articles

Association of Cutaneous Immune-related Adverse Events with Overall Survival and Progression-free Survival in Oncology Patients Receiving Immune Checkpoint Inhibitors: A Prospective Study of 189 Patients in a Spanish Tertiary Care Hospital.

Juan-Carpena G, Martinez Banaclocha N, Palazon Cabanes J, Niveiro-de Jaime M, Betlloch Mas I, Blanes-Martinez M Acta Derm Venereol. 2025; 105:adv42023.

PMID: 39749393 PMC: 11697139. DOI: 10.2340/actadv.v105.42023.

Cutaneous adverse events due to checkpoint inhibitors - a retrospective analysis at a tertiary referral hospital in Switzerland 2019-2022.

Furrer-Matcau C, Sieber C, Lehnick D, Brand C, Hug B Front Oncol. 2024; 14:1485594.

PMID: 39703836 PMC: 11655322. DOI: 10.3389/fonc.2024.1485594.

MET amplification correlates with poor prognosis and immunotherapy response as a subtype of melanoma: a multicenter retrospective study.

Cai X, Lin J, Li C, Xu T, Chen C, Lan B BMC Cancer. 2024; 24(1):1384.

PMID: 39528978 PMC: 11555915. DOI: 10.1186/s12885-024-13163-z.

Emerging immunologic approaches as cancer anti-angiogenic therapies.

Azimi M, Manavi M, Afshinpour M, Khorram R, Vafadar R, Rezaei-Tazangi F Clin Transl Oncol. 2024; .

PMID: 39294514 DOI: 10.1007/s12094-024-03667-2.

Generalized Eruptive Keratoacanthoma (GEKA) after Pfizer mRNABNT162b2 (Comirnaty) COVID-19 Vaccination Successfully Treated with Cemiplimab.

Ilaria P, Nevena S, Ersilia T, Federica T, Felice F, Agnieszka Ewa D Viruses. 2024; 16(8).

PMID: 39205234 PMC: 11360220. DOI: 10.3390/v16081260.

References

Domingo-Musibay E, Murugan P, Giubellino A, Sharma S, Steinberger D, Yuan J . Near complete response to Pembrolizumab in microsatellite-stable metastatic sebaceous carcinoma. J Immunother Cancer. 2018; 6(1):58. PMC: 6006706. DOI: 10.1186/s40425-018-0357-3. View

Haug V, Behle V, Benoit S, Kneitz H, Schilling B, Goebeler M . Pembrolizumab-associated mucous membrane pemphigoid in a patient with Merkel cell carcinoma. Br J Dermatol. 2018; 179(4):993-994. DOI: 10.1111/bjd.16780. View

Martinez S, Barr K, Canter R . Rare tumors through the looking glass: an examination of malignant cutaneous adnexal tumors. Arch Dermatol. 2011; 147(9):1058-62. DOI: 10.1001/archdermatol.2011.229. View

Fischer S, Ali O, Jochum W, Kluckert T, Flatz L, Siano M . Anti-PD-1 Therapy Leads to Near-Complete Remission in a Patient with Metastatic Basal Cell Carcinoma. Oncol Res Treat. 2018; 41(6):391-394. DOI: 10.1159/000487084. View

Walocko F, Scheier B, Harms P, Fecher L, Lao C . Metastatic Merkel cell carcinoma response to nivolumab. J Immunother Cancer. 2016; 4:79. PMC: 5109712. DOI: 10.1186/s40425-016-0186-1. View

Assam J, Powell S, Spanos W . Unresectable cutaneous squamous cell carcinoma of the forehead with mutation showing dramatic response to Programmed Cell Death Protein 1 Inhibitor Therapy. Clin Skin Cancer. 2018; 1(1):26-29. PMC: 5766284. DOI: 10.1016/j.clsc.2016.11.001. View

Pico de Coana Y, Wolodarski M, Poschke I, Yoshimoto Y, Yang Y, Nystrom M . Ipilimumab treatment decreases monocytic MDSCs and increases CD8 effector memory T cells in long-term survivors with advanced melanoma. Oncotarget. 2017; 8(13):21539-21553. PMC: 5400604. DOI: 10.18632/oncotarget.15368. View

Cohen P, Kato S, Goodman A, Ikeda S, Kurzrock R . Appearance of New Cutaneous Superficial Basal Cell Carcinomas during Successful Nivolumab Treatment of Refractory Metastatic Disease: Implications for Immunotherapy in Early Versus Late Disease. Int J Mol Sci. 2017; 18(8). PMC: 5578053. DOI: 10.3390/ijms18081663. View

Kandl T, Sagiv O, Curry J, Ning J, Ma J, Hudgens C . High expression of PD-1 and PD-L1 in ocular adnexal sebaceous carcinoma. Oncoimmunology. 2018; 7(9):e1475874. PMC: 6140585. DOI: 10.1080/2162402X.2018.1475874. View

10.

Ascierto P, Long G, Robert C, Brady B, Dutriaux C, Di Giacomo A . Survival Outcomes in Patients With Previously Untreated BRAF Wild-Type Advanced Melanoma Treated With Nivolumab Therapy: Three-Year Follow-up of a Randomized Phase 3 Trial. JAMA Oncol. 2018; 5(2):187-194. PMC: 6439558. DOI: 10.1001/jamaoncol.2018.4514. View

11.

Zhao C, Tella S, Del Rivero J, Kommalapati A, Ebenuwa I, Gulley J . Anti-PD-L1 Treatment Induced Central Diabetes Insipidus. J Clin Endocrinol Metab. 2017; 103(2):365-369. PMC: 5800826. DOI: 10.1210/jc.2017-01905. View

12.

Kluger H, Zito C, Turcu G, Baine M, Zhang H, Adeniran A . PD-L1 Studies Across Tumor Types, Its Differential Expression and Predictive Value in Patients Treated with Immune Checkpoint Inhibitors. Clin Cancer Res. 2017; 23(15):4270-4279. PMC: 5540774. DOI: 10.1158/1078-0432.CCR-16-3146. View

13.

DAngelo S, Russell J, Lebbe C, Chmielowski B, Gambichler T, Grob J . Efficacy and Safety of First-line Avelumab Treatment in Patients With Stage IV Metastatic Merkel Cell Carcinoma: A Preplanned Interim Analysis of a Clinical Trial. JAMA Oncol. 2018; 4(9):e180077. PMC: 5885245. DOI: 10.1001/jamaoncol.2018.0077. View

14.

Keilholz U, Mehnert J, Bauer S, Bourgeois H, Patel M, Gravenor D . Avelumab in patients with previously treated metastatic melanoma: phase 1b results from the JAVELIN Solid Tumor trial. J Immunother Cancer. 2019; 7(1):12. PMC: 6335739. DOI: 10.1186/s40425-018-0459-y. View

15.

Tawbi H, Burgess M, Bolejack V, Van Tine B, Schuetze S, Hu J . Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol. 2017; 18(11):1493-1501. PMC: 7939029. DOI: 10.1016/S1470-2045(17)30624-1. View

16.

Winkler J, Schneiderbauer R, Bender C, Sedlaczek O, Frohling S, Penzel R . Anti-programmed cell death-1 therapy in nonmelanoma skin cancer. Br J Dermatol. 2016; 176(2):498-502. DOI: 10.1111/bjd.14664. View

17.

Lesokhin A, Ansell S, Armand P, Scott E, Halwani A, Gutierrez M . Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study. J Clin Oncol. 2016; 34(23):2698-704. PMC: 5019749. DOI: 10.1200/JCO.2015.65.9789. View

18.

Hodi F, ODay S, Mcdermott D, Weber R, Sosman J, Haanen J . Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010; 363(8):711-23. PMC: 3549297. DOI: 10.1056/NEJMoa1003466. View

19.

Byrne E, Fisher D . Immune and molecular correlates in melanoma treated with immune checkpoint blockade. Cancer. 2017; 123(S11):2143-2153. PMC: 5445935. DOI: 10.1002/cncr.30444. View

20.

Kratzsch D, Simon J, Ponitzsch I, Ziemer M . Lethal thrombocytopenia in a patient treated with avelumab for metastatic Merkel cell carcinoma. J Dtsch Dermatol Ges. 2018; 17(1):73-75. DOI: 10.1111/ddg.13722. View