Phase 1/2 study of liposomal irinotecan plus S-1 for metastatic pancreatic cancer refractory to gemcitabine-based treatment

Abstract

Background

Liposomal irinotecan (nal-IRI) plus fluorouracil/folinic acid (5-FU/LV) improves survival in gemcitabine-refractory metastatic pancreatic cancer (PC) but requires a central venous port. S-1, an oral fluoropyrimidine with proven efficacy in PC, may replace 5-FU/LV in nal-IRI plus 5-FU/LV, potentially enhancing both convenience and antitumor effect.

Methods

This single-arm, open-label, phase 1/2 study included patients with histologically or cytologically confirmed adenocarcinoma, aged 20–80 years, an Eastern Cooperative Oncology Group performance status of 0–1, with metastatic disease, and refractory to gemcitabine-based treatment. The primary endpoint in phase 1 part was the frequency of dose-limiting toxicity (DLT) to nal-IRI plus S-1. The primary endpoint in phase 2 part was overall survival. This trial was registered in the Japan Registry of Clinical Trials database (jRCTs031210040).

Results

In phase 1 part, one patient with DLT was observed at nal-IRI 70 mg/m² (day 1) with S-1 80 mg/m²/day (day 1–7) in a 2-week cycle, establishing this as the recommended phase 2 dose (RP2D). Forty-nine patients from phase 1 (n = 6) and phase 2 part (n = 43) were treated with the RP2D, and their results were pooled. Median overall survival was 10.3 months (95 % confidence interval, 8.1–12.0 months). A confirmed partial response was achieved in 10 patients (20.4 %). The most frequent treatment-emergent adverse events were hypoalbuminemia (98.0 %), anemia (98.0 %), and anorexia (81.6 %). There were no treatment-related deaths.

Conclusions

This study demonstrated that nal-IRI plus S-1 exhibited promising efficacy and an acceptable safety profile in patients with metastatic PC refractory to gemcitabine-based treatment.