Case report: Spatiotemporal HER2 heterogeneity in AFP-producing gastric cancer: navigating long-term survival with molecularly-guided therapy in a refractory case.

Alpha-fetoprotein-producing gastric cancer (AFPGC) is a rare, aggressive subtype with poor prognosis. We report a metastatic AFPGC case showing spatiotemporal human epidermal growth factor receptor 2 (HER2) heterogeneity. Following progression on first-line FLOT chemotherapy, the 65-year-old male received second-line apatinib plus programmed death-1 (PD-1) inhibitor. At progression (27 months), a lymph node biopsy revealed HER2 conversion from 1+ to 3 +. Third-line anti-HER2 antibody-drug conjugate (ADC) DP303c rapidly achieved partial response with normalized AFP. Despite treatment discontinuation due to neurotoxicity after 5 cycles, response persisted. Overall survival reached 79 months. This case highlights: 1) efficacy of anti-angiogenic and immunotherapy in AFPGC; 2) necessity of re-biopsy for detecting HER2 heterogeneity; and 3) potent activity of ADCs against HER2-converted metastases, enabling remarkable survival through sequential precision therapy.