Complete and Persistent Response to Immunotherapy in Highly Pretreated MSS TMB-High Pancreatic Adenocarcinoma: A Case Report and Literature Review

Despite advances in precision medicine, therapeutic options for pancreatic adenocarcinomas are limited, alongside a significant increase in incidence and mortality in recent years. We present the case of an exceptional response to immunotherapy in a heavily pre-treated pancreatic adenocarcinoma. The patient is a 73-year-old man that was diagnosed in 2017 with locally advanced pancreatic adenocarcinoma. He underwent different lines of chemotherapy and after exhausting standard treatment options, he practiced the FoundationOne® CDx analysis (Foundation Medicine, Inc., Cambridge, MA, USA), that pointed out a High Tumor mutational burden that permitted our Oncology Center to request Pembrolizumab 200mg flat dose q 21 as an off-label therapy. The patient started the treatment in July 2021 and is still ongoing, having achieved a complete radiological response of hepatic metastases. Although immunotherapy is not part of the standard treatment paradigm for advanced pancreatic cancer, our case suggests that it may provide substantial and durable clinical benefit in a small molecularly selected subgroup of patients who have exhausted conventional therapeutic options, highlighting the critical role of comprehensive molecular profiling in identifying actionable treatment opportunities.