J. Beam1, N. Rademacher2, B. Hollenquest3, J. Slatton1, E. Ross3, J. McConathy4, K. Broman2 1University Of Alabama at Birmingham, Heersink School Of Medicine, Birmingham, Alabama, USA 2University Of Alabama at Birmingham, Department Of Surgery, Birmingham, Alabama, USA 3University Of Alabama at Birmingham, Institute For Cancer Outcomes And Survivorship, Birmingham, Alabama, USA 4University Of Alabama at Birmingham, Department Of Radiology, Birmingham, Alabama, USA
Introduction:
After immune checkpoint inhibitor treatment showed efficacy in advanced Merkel Cell Carcinoma (MCC), there has been increasing use of neoadjuvant immunotherapy for patients with resectable stage III and IV disease, with some patients having pathologic complete response.. The value of surgical resection for these patients is uncertain. The purpose of this study is to evaluate the use of neoadjuvant immunotherapy for resectable stage III MCC involving lymph nodes and report pathologic response rates and early outcomes.
Methods:
A retrospective cohort study was conducted among patients with stage III MCC who were treated at our NCI-designated comprehensive cancer center from May 2021 to December 2023 and received neoadjuvant checkpoint inhibitor therapy prior to surgery. Pathologic responses were abstracted from the electronic medical record. Tumors were subjected to usual pathologic assessment, with presence or absence of viable tumor and % with major pathologic response (defined as <10% viable tumor) reported. Descriptive statistics were used to report pathologic response.
Results:The cohort included 9 patients who had a median age of 71 years (interquartile range (IQR) 66-77 years), were all white and non-hispanic, and were 56% male (N=5). Sixty-seven percent (N=6) of patients had synchronous primary tumors and nodal disease, while 33% (N=3) presented with nodal recurrence with unknown primary or after treatment of a primary tumor. Most patients 67% (N=6) received pembrolizumab as pre-operative immunotherapy, while others received avelumab or nivolumab. Six of 9 patients continued immunotherapy following surgery. All patients went on to complete lymphadenectomy after neoadjuvant treatment, yielding a median of 17 nodes removed (IQR 7-24), and a median of 1 positive node (IQR 0-2). Forty-four percent of patients had no viable tumor on final pathology, and 56% (N=5) had major pathologic response. One of 9 patients recurred at median follow up of 420 days (IQR 237-434) and this person died of MCC.
Conclusion:
Over 40% of patients had a pathologic complete response to neaodjuvant immunotherapy and more than 50% had a major pathologic response. While long term outcomes from neoadjuvant therapy for MCC are awaited, these results validate prior trial findings in a real-world cohort and suggest that some patients may be eligible for surgical de-escalation. Future work will address how patients who are likely to have a major pathologic response can be identified clinically for participation in surgical de-escalation trials by correlating imaging parameters with pathologic response assessment.