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

INTRODUCTION: Immuno-checkpoint inhibitors (ICIs) represent the backbone for the first line combination therapies of metastatic renal cell carcinoma (mRCC) but their advantage in the IMDC favourable risk compared to sunitinib is debated. To estimate their efficacy we present an individual patient data (IPD) meta-analysis METHODS: A systematic literature search from 2015 to 2024 was conducted on the MEDLINE. Five phase III studies, 1088 patients overall, were analyzed according to PRISMA statement. (JAVELIN RENAL 101, CHECKMATE 214, KEYNOTE 426, CHECKMATE 9ER, CLEAR). An IPD meta-analysis was performed by reconstructing IPD from Kaplan-Meier curves. Primary endpoints were Progression Free Survival (PFS) and overall Survival (OS) in favorable risk patients comparing ICI-based therapies versus sunitinib as well as versus each other. RESULTS: For OS, there was a statistically significant superiority of Pembrolizumab-Lenvatinib rather than Nivolumab-Cabozantinib (HR 0.56 CI 95% 0.34 -0.94), and, even non-statistically significant, vs Pembrolizumab-Axitinib (HR 0.68), vs Avelumab-Axitinib (HR 0.93), and vs Nivolumab + Ipilimumab (HR 0.95). Considering PFS, Pembrolizumab-Lenvatinib showed a significant advantage when compared to Avelumab-Axitinib (HR 0.66 CI 95% 0.46-0.96), to Nivolumab-Cabozantinib (HR 0.61 CI 95% 0.42 -0.90), to Nivolumab-Ipilimumab (HR 0.59 CI 95% 0.42-0.82) and to Pembrolizumab-Axitinib (HR 0.71 CI 95% 0.50 - 0.71). CONCLUSIONS: In IMDC-favorable risk mRCC patients, Pembrolizumab + Lenvatinib showed the best PFS, while none of the arms showed a statistically significant OS advantage versus sunitinib. Further studies would help identify specific patients’ subgroups and establish more personalized treatment decisions.

Abstract licence: CC BY-NC-ND