HER2-positive metastatic gastric cancer responding to trastuzumab deruxtecan rechallenge

What happened, in summary

A 67-year-old man was diagnosed with poorly differentiated gastric cardia adenocarcinoma with liver and lymph-node metastases. The tumor strongly overexpressed HER2. He began S-1 plus oxaliplatin with trastuzumab, but the cancer progressed after 6 cycles. Paclitaxel plus ramucirumab and then irinotecan also failed to control the disease.

He next entered a phase I trial of trastuzumab deruxtecan as fourth-line treatment. The best response was partial, with 5.6 months without progression before the cancer advanced again. Immune checkpoint inhibitor therapy was subsequently given, and a long treatment-free interval followed after an osteoporotic sacral fracture.

When swallowing difficulty later worsened, CT and endoscopy showed further growth of the gastric tumor. A new biopsy confirmed that HER2 expression was still present, including HER2 gene amplification. Trastuzumab deruxtecan was therefore restarted as seventh-line treatment in March 2021. His condition improved after the first cycle, and after 3 cycles imaging showed clear tumor shrinkage. Endoscopy also showed regression of the primary gastric lesion. At the latest follow-up he remained on trastuzumab deruxtecan without progression or treatment-related adverse events.