A case report described durable disease control with second-line trastuzumab deruxtecan in a 63-year-old patient with HER2-positive metastatic gastroesophageal junction adenocarcinoma. After rapid progression on first-line chemoimmunotherapy, the patient achieved 23 months of progression-free survival on second-line therapy. While single-patient reports cannot establish effectiveness across populations, the clinical course adds to real-world narratives of antibody-drug conjugate durability in post-progression settings. For developers, it can inform subgroup hypotheses and the selection of outcomes to track in broader studies.