Should adjuvant nivolumab be used in surgically resected Merkel cell carcinoma patients?
Mené sur 179 patients atteints d'un carcinome à cellules de Merkel traité par résection, cet essai multicentrique randomisé de phase II évalue l'efficacité, du point de vue de la survie sans maladie et de la survie globale, et la toxicité d'une immunothérapie adjuvante par nivolumab
Merkel cell carcinoma (MCC), a life-threatening cancer, accounts for less than 1% of all skin malignancies and occurs mostly in White individuals. 1 Merkel cell polyomavirus infection and ultraviolet exposure contribute to carcinogenesis, and risk factors include advanced age, immunosuppression, and male sex. 1 Immune checkpoint inhibitors (ICIs) have improved the prognosis of patients with unresectable MCC. 2 In treatment-naive patients, the anti-programmed death-1 (PD-1) monoclonal antibody (mAb) pembrolizumab 3 induced an overall response rate (ORR) of 58%, and anti-programmed death-1 ligand (anti-PD-L1) mAb avelumab 4 induced an ORR of 40%. However, complete response rates were only 24% for pembrolizumab and 14% for avelumab, and median progression-free survival only 16·8 months for pembrolizumab and 4·1 months for avelumab. 3 , 4 Moreover, contrary to advanced melanoma, another PD-1-mAb-sensitive cancer, ICI responses in MCC might not be durable off-treatment, including in patients who have a complete response. 5 The combination of low-dose ipilimumab with nivolumab was associated with higher ORR in patients with ICI-naive MCC, with long-lasting responses, and to some benefit in patients with ICI-resistant MCC, 6 but at the cost of frequent adverse events. Thus, improved strategies are required, including the adjuvant approach. Adjuvant therapy aims to reduce the recurrence rate in patients with surgically excised high-risk cancer and to improve survival. Pembrolizumab and nivolumab have shown improved relapse-free and distant metastasis-free survival, with a hazard ratio of approximately 0·6 compared with placebo in patients with American Joint Committee on Cancer stage IIB-IIC, IIIA-D melanoma.