Case Reports in Oncology
Durable Complete Response to γ-Secretase Inhibition in NOTCH1-Mutated Esophageal Adenocarcinoma: A Case Report
By David Parker, Christopher Gale, Carolina Rosario Rodriguez and 4 others.
Abstract
Introduction
The use of molecular profiling of tumor tissue to identify potential targeted therapies for cancer patients has been an increasingly useful tool in personalized medicine.
Case presentation
Here, we present a case of a 60-year-old gentleman who was initially diagnosed in 2012 with stage II esophageal adenocarcinoma. Neoadjuvant chemoradiation followed by esophagectomy was shortly followed by recurrence in the liver and lung. Despite numerous local and systemic treatments over the subsequent three years, his disease persisted, and he was considering hospice care. Comprehensive genomic profiling revealed three somatic alterations in NOTCH1 in the tumor tissue. These mutations are rarely found in esophageal adenocarcinoma and are thus not common treatment targets that would have been considered for this patient in the absence of molecular profiling data. These molecular findings informed the patient’s enrollment in a phase 1 clinical trial with a pan-Notch signaling inhibitor targeting ă-secretase. After less than one year of treatment, the patient experienced a complete response; treatment was discontinued after two years, and he remained disease free for over 8 years before passing away from an unrelated cardiac event.
