Avelumab 200mg/10ml solution for infusion vials

Objective: Merkel cell carcinoma (MCC) is a rare and aggressive form of skin cancer. Although immunotherapy has transformed MCC management, published data remain limited. This comprehensive review evaluates current evidence on immune checkpoint inhibitors (ICIs) in MCC, in relation to other treatment modalities such as surgery and radiotherapy. Methods: Peer-reviewed articles published between January 2000 and August 2025 were searched manually in four databases: Scopus, ScienceDirect, PubMed and MEDLINE, using the keywords "Merkel cell carcinoma" AND "immunotherapy" AND "immune checkpoint inhibitors". The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology was employed. Results: ICIs can be given in different settings: (A) Neoadjuvant: The CheckMate 358 trial reported a 54.5% response rate among 33 radiologically evaluable patients treated with nivolumab, each showing over 30% tumor reduction. (B) Adjuvant: (1) The ADMEC-O phase II trial demonstrated improved disease-free survival with adjuvant nivolumab. (2) The ADAM phase III trial evaluates adjuvant avelumab in node-positive patients post-surgery/radiation, with common side effects including nausea, fatigue, and itching. (3) STAMP, a phase III trial, investigates pembrolizumab in stage I-III MCC. Both ADAM and STAMP have completed accrual and results are pending. (C) Primary therapy: KEYNOTE-017 and JAVELIN trials reported a 60% overall response rate and ~40% 3-year progression-free survival with first-line pembrolizumab or avelumab. Both agents also show promise as salvage therapies. Conclusions: ICIs demonstrate encouraging outcomes in MCC across various treatment stages. Continued research is essential to optimize treatment timing and integrate multimodal therapies.

Abstract licence: CC BY

Merkel cell carcinoma (MCC) is a rare, aggressive neurocutaneous malignancy associated with ultraviolet damage, immunosuppression, and Merkel cell polyoma virus infection. Periocular MCC is uncommon but has high rates of local recurrence and metastasis and presents unique therapeutic challenges due to functional and cosmetic considerations. Immune checkpoint inhibitor (ICI) therapy has shown efficacy in systemic MCC; however, evidence for periocular use is limited to small case series and reports without consolidated evidence or consensus. Thus, this study summarizes and evaluates the effectiveness and safety of ICIs for periocular MCC. A systematic literature search across PubMed, Embase, and Web of Science was conducted according to PRISMA guidelines. Randomized and nonrandomized studies, case series, and case reports in English describing ICI use for periocular MCC were included. Non-human studies, non-periocular MCC, and reports without ICI treatment were excluded. Extracted data included patient demographics, tumor characteristics, treatment regimen, and patient outcomes. Seven studies reporting ten patients were included. Treatment regimens consisted of pembrolizumab (n = 6) and avelumab (n = 3), or both medications (n = 1). At a mean follow-up of 11.4 ± 9.0 months, nine patients had complete response (90%); only one patient developed subsequent distant progression despite local response. Patients with both localized periocular disease and metastatic involvement demonstrated favorable responses to ICI. Adverse effects were infrequent and typically mild; only one patient discontinued therapy due to adverse effects. ICIs may be an effective and well-tolerated treatment for local and advanced periocular MCC; however, larger, prospective studies are needed.

Abstract licence: CC BY-NC-SA

AimProgrammed death (ligand) 1 inhibitors (e.g., avelumab, pembrolizumab, and retifanlimab) are first-line treatment options for patients with locally advanced or metastatic Merkel cell carcinoma (MCC). In the absence of comparative and randomized trials, we aimed to systematically identify and synthesize real-world evidence (RWE) on the effectiveness and safety of immunotherapies in patients with advanced MCC.Methods & materialsMEDLINE and Embase searches were conducted for observational RWE studies in locally advanced or metastatic MCC from January 2017 to December 2023. Avelumab was the only immunotherapy with sufficient data for analysis. Landmark 12-month overall survival (OS) and progression-free survival (PFS) were assessed by meta-analysis.ResultsScreening of 1731 records identified 37 publications eligible for inclusion (16 unique studies), of which eight were included in the meta-analysis. In line with results from the JAVELIN Merkel 200 trial, pooled 12-month OS rates of 77.7% in stage III and 63.0% in stage IV MCC and 12-month PFS rates of 53.3% and 39.3%, respectively, were estimated. Although safety data were insufficient for meta-analysis, two retrospective studies reported lower adverse event rates than JAVELIN Merkel 200.ConclusionsThe results of this study support broader use of avelumab in advanced MCC.

Abstract licence: CC BY