Evaluation of the Impact of Adjuvant Immunotherapy in Merkel Cell Carcinoma

BACKGROUND: The role of adjuvant immunotherapy (IO) in the treatment of Merkel cell carcinoma (MCC) is currently being explored in clinical trials. Here we aim to evaluate the real-world impact of adjuvant IO on survival in patients with MCC. METHODS: A retrospective analysis of the National Cancer Database was performed to identify patients with stage I-III MCC. Our main predictor of interest was IO in an adjuvant setting, stratified by receipt of radiotherapy (RT). A multivariable Cox proportional hazards regression model with inverse probability treatment weighting was used to estimate overall survival. RESULTS: A total of 353 patients received adjuvant IO, while 5,340 underwent surgery without adjuvant therapy. Among patients who received adjuvant IO, 10.2% had stage I disease, 7.1% stage II, and 82.7% stage III. Overall, adjuvant IO was not associated with a difference in survival (hazard ratio [HR], 1.04; 95% CI, 0.86-1.26). Stratified analyses by stage demonstrated similar findings (stage I: HR, 1.4; 95% CI, 0.79-2.50; stage II: HR, 1.45; 95% CI, 0.67-3.13; stage III: HR, 0.98; 95% CI, 0.79-1.20). However, when an interaction term with RT was introduced with adjuvant IO, both treatments were associated with improved survival compared with surgery alone (HR, 0.53; 95% CI, 0.28-0.99), whereas adjuvant IO without RT was not associated with a significant survival difference (HR, 1.14; 95% CI, 0.83-1.60). CONCLUSIONS: The association between adjuvant IO on survival may be modified by RT, which should be considered when interpreting current adjuvant IO trials in MCC.