Phase II clinical trial of nab-paclitaxel plus cisplatin plus gemcitabine (NABPLAGEM) in patients with untreated advanced pancreatic cancer

Background: A previous phase IB/II study of nab-paclitaxel + cisplatin + gemcitabine (NABPLAGEM) in 25 patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDAC) demonstrated favorable results. This phase II study was conducted to further evaluate the safety, efficacy, and impact on quality of life (QOL) of NABPLAGEM in a multi-center setting. Methods: Participants were ≥18 years; had measurable PDAC; Karnofsky performance status of ≥70%; life expectancy ≥12 weeks; <grade 2 pre-existing peripheral neuropathy, and adequate hematologic, hepatic, and renal function. Study treatment included nab-paclitaxel (125 mg/m²), cisplatin (25 mg/m²), and gemcitabine (1000 mg/m²), on Days 1 and 8 of a 21-day cycle. The primary endpoint was 12-month overall survival (OS). Results: A total of 42 patients were enrolled with a median age of 66.8 years, a majority were male (66.7%) and white (76.2%). Treatment-related adverse events ≥grade 3 were: thrombocytopenia (64.3%), anemia (47.6%), and neutropenia (26.1%). OS at 12 months was 38.1%, with 12% of patients alive as of last contact (20–40+ months). In 37 evaluable participants responses included: partial response (40.5%), stable disease (43.2%), and progressive disease (16.2%), with overall response rate of 40.5% and DCR of 88.6%. Statistically significant improvement in QOL was reported during the first three cycles. Conclusion: The primary objective of achieving a 12-month survival comparable to the previous phase Ib/II NABPLAGEM PCRT 12-001 was not achieved in this trial. NABPLAGEM has efficacy in advanced PDAC, demonstrating early disease control noted by improvement in patient symptoms, decrease in tumor volume and tumor markers within the first 9 weeks. The activity and tolerability make this a suitable regimen for further testing in the neoadjuvant setting.