166P - Combination of 5-fluorouracil (FU), interferon (IFN)-alpha2, and nivolumab in unresectable fibrolamellar liver cancer

Background

Fibrolamellar liver cancer (FLC) is a rare malignancy involving multidisciplinary approaches including surgery, liver-directed, and systemic treatment. Combination therapy with 5-fluorouracil (FU) and interferon (IFN)-a2 has long been used for FLC. We hypothesized that addition of anti-PD1 to 5-FU+IFN-a2 may further improve clinical outcome and lead to a favorable modulation of tumor microenvironment.

Methods

We treated 3 patients with unresectable FLC with 5-FU+IFN-a2+nivolumab (N): 5-FU 200 mg/m² 7-day-on/7-day-off, IFN-a2 (4 million U/m² 3 times/week with 5-FU) for 8 weeks, followed by on-treatment biopsy and addition of N 480 mg every 4 weeks to 5-FU+IFN-a2. Tumor tissues were collected under an IRB-approved protocol.

Results

Two patients (26, 29 years) initially had unresectable FLC with a 6.1 cm tumor in seg IV liver invading the common hepatic duct, and a 19.5 cm tumor, peritoneal nodules, and abdominal lymph nodes. After 9 and 5 months of therapy, unresectable tumors were converted to resectable ones: the former had L hepatectomy and bile duct resection; the latter, L hepatectomy, resection of the omentum, spleen, L diaphragm, and lymph node dissection. Both patients completed adjuvant therapy with the same regimen, having no recurrence. The third patient (20 years) had multifocal liver tumors with peritoneal carcinomatosis and lymph nodes. He received treatment for 5 months and achieved stable disease, followed by hepatic tumor bleeding leading to treatment discontinuation. All 3 patients had an increase of CD8+T cells in on-treatment (5-FU+IFN-a2, week 8), compared to pre-treatment biopsies. The available surgical tumor tissues (s/p 5-FU+IFN-a2+N) were also evaluated in patients who underwent surgery with conversation of unresectable to resectable disease, showing a further increase of CD8+T cells.

Conclusions

This clinical outcome of converting an unresectable disease to a resectable one with tumors significantly decreasing in size suggests synergy of 5-FU+IFN-a2 combined with anti-PD1. The robust increased infiltration of CD8+T cells on 5-FU+IFN-a2+N may explain this clinical efficacy. Detailed immune analyses with gene expression profiling will be presented at ESMO Immuno-Oncology Meeting.

Legal entity responsible for the study

The authors.

Funding

Fibrolamellar Cancer Foundation.

Disclosure

All authors have declared no conflicts of interest.