Liposomal irinotecan, oxaliplatin, and S-1 as first-line therapy for patients with locally advanced or metastatic pancreatic adenocarcinoma (NASOX): A multicenter phase I/IIa study

• Published in: European journal of cancer (1990) 2024-09, Vol.208, p.114194, Article 114194
• Main Authors: Jeong, Hyehyun, Kim, Bum Jun, Lee, Choong-kun, Park, Inkeun, Zang, Dae Young, Choi, Hye Jin, Lee, Sang Soo, Park, Do Hyun, Song, Tae Jun, Oh, Dongwook, Moon, Sung-Hoon, Kim, Kyu-pyo, Wainberg, Zev, Ryoo, Baek-Yeol, Yoo, Changhoon
• Format: Article
• Language: English
• Subjects: Liposomal irinotecan; Oxaliplatin; Pancreatic adenocarcinoma; S-1
• ISSN: 0959-8049; 1879-0852; 1879-0852
• DOI: 10.1016/j.ejca.2024.114194

This multicenter phase I/IIa study aimed to determine the recommended phase II dose (RP2D) and evaluate the safety and preliminary efficacy of liposomal irinotecan (nal-IRI), oxaliplatin, and S-1 (NASOX) as first-line treatment for advanced pancreatic adenocarcinoma. Patients with locally advanced or metastatic pancreatic adenocarcinoma without prior systemic treatment for advanced disease, aged ≥ 19 years, with measurable disease, and Eastern Cooperative Oncology Group performance status of 0–1 were eligible. The primary endpoints were to determine the dose-limiting toxicity (DLT) in the phase I cohort and overall response rate (ORR) in the phase IIa cohort. The intention-to-treat (ITT) analysis included patients who received the RP2D. In phase I, seven patients were screened, and six were assessed for DLT. None experienced DLT during the first cycle. The RP2D was determined as nal-IRI 50 mg/m2 and oxaliplatin 60 mg/m2 on day 1, S-1 40 mg/m2 twice daily on days 1–7 every 14 days. For the ITT (N = 41; 7, and 34 from phases I and IIa, respectively), the most common grade 3–4 treatment-emergent adverse events were neutropenia (31.7 %), enterocolitis (9.8 %), anorexia (7.3 %), and diarrhea (2.4 %). The ORR was 58.5 % (1 complete, and 23 partial responses). Two underwent conversion surgery; both achieved R0 resection. With median follow-up of 17.5 months, median progression-free survival was 6.5 months (95 % confidence interval [CI], 5.0–8.1) and median overall survival was 11.4 months (95 % CI, 9.8–15.5). NASOX exhibited a manageable safety profile and encouraging efficacy outcomes consistent with NALIRIFOX, showing potential to replace infusional 5-fluorouracil with oral S-1 in the triplet regimen. •In this Ph I/IIa trial, patients with advanced PDAC received 1 L NASOX every 2 weeks.•RP2D: nal-IRI 50 mg/m2, oxaliplatin 60 mg/m2 on D1, S-1 40 mg/m2 BID on D1–7.•ORR was 58.5 %, median PFS was 6.5 months, and median OS was 11.4 months.•Safety profiles were manageable.•NASOX may improve patient convenience while showing efficacy comparable to NALIRIFOX.