Complete and durable remission in a patient with brain metastasis from gastric cancer treated with SRS followed by RC48 plus camrelizumab after progression on chemo-immunotherapy: a case report and literature review.

BACKGROUND: Brain metastasis from gastric cancer carries a dismal prognosis, with median overall survival of only 3-6 months. Patients who progress on immune checkpoint inhibitor (ICI)-containing regimens have limited salvage options. HER2-low expression (IHC 1+ or IHC 2+/FISH-negative), historically excluded from anti-HER2 therapy, has now emerged as a novel therapeutic target for antibody-drug conjugates (ADCs) such as RC48 (disitamab vedotin).

CASE SUMMARY: A 52-year-old male with HER2-low (IHC 2+/FISH-negative), PD-L1 CPS 5, microsatellite-stable (MSS) advanced gastric cancer received first-line XELOX plus camrelizumab, achieving a partial response (PR) followed by progression with new brain metastases. After stereotactic radiosurgery (SRS) for a solitary brain lesion, he received RC48 plus camrelizumab for eight months, achieving PR. Treatment was discontinued due to grade 2 pneumonitis (managed without corticosteroids). Complete response (CR) was achieved during the follow-up. The patient has been off therapy over three years and remains disease-free.

LITERATURE REVIEW: We review the current evidence for HER2-low gastric cancer treatment, ADC plus ICI combinations, the potential immunomodulatory role of radiotherapy (including the abscopal effect) as it may contribute to systemic antitumor responses when combined with ICIs, and treatment-free remission following ICI discontinuation.

CONCLUSION: This is the first report of durable, treatment-free survival over 36 months in an ICI-refractory, HER2-low gastric cancer patient with brain metastasis suggests that RC48 can reverse PD-1 resistance, SRS may prime systemic antitumor immunity, and finite-duration ADC plus ICI therapy can establish long-lasting immunological memory.