Pancreatic ductal adenocarcinoma with ITSN1-ALK fusion: sustained response to alectinib with 19-month progression-free survival.

BACKGROUND

Pancreatic ductal adenocarcinoma (PDAC) harboring ALK fusions is exceptionally rare, with limited data on clinical outcomes with ALK inhibitor therapy.

CASE SUMMARY: A 70-year-old man presented with stage IV PDAC (pancreatic tail primary with liver and lymph node metastases). Following progression on first-line gemcitabine/nab-paclitaxel, tumor next-generation sequencing identified an ITSN1-ALK fusion (62.12% abundance) and TP53 mutation. The patient received alectinib 600 mg twice daily beginning at Month 4. Tumor markers declined markedly (CA19-9 from 234 to 12.7 U/mL by Month 7), and radiographic stability was maintained through Month 22. Upon progression at Month 23, treatment was switched to lorlatinib followed by capecitabine plus nimotuzumab. The patient remains alive at last follow-up (Month 29). Progression-free survival on alectinib was 19 months-substantially exceeding the median of 5.0 months reported for ALK fusion-positive gastrointestinal cancers.

CONCLUSION

This first report of ITSN1-ALK fusion in PDAC demonstrates that ALK inhibition can produce durable, clinically meaningful benefit. This case reinforces the importance of comprehensive genomic profiling in KRAS-wildtype PDAC to identify actionable rare fusions.

IMPLICATIONS FOR PRACTICE: Oncologists should consider broad next-generation sequencing, including fusion detection, for patients with KRAS-wildtype PDAC. When an ALK fusion is identified, ALK inhibitor therapy can yield durable disease control.