Abstract
Abstract
Background: Treatment options for advanced pancreatic ductal adenocarcinoma (PDAC) beyond first-line 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) are limited, and patients are commonly treated with gemcitabine and nab-paclitaxel. The aim of this study was to determine whether the addition of a MUC5AC antibody, NPC-1C, could improve the efficacy of second-line gemcitabine and nab-paclitaxel in advanced PDAC. Methods: This study was a multicenter, open label, randomized phase II clinical trial (NCT01834235) for patients with metastatic or locally advanced PDAC who had disease progression on first-line FOLFIRINOX or a FOLFIRINOX-like regimen. Eligible patients had tumors with >20% MUC5AC expression as assessed by centralized immunohistochemistry review. Patients were randomly assigned (1:1 ratio) to receive gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 on days 1, 8, and 15 every 4-week cycle with or without IV NPC-1C 1.5 mg/kg every two weeks. The primary endpoint was overall survival (OS). Secondary endpoints were progression free survival (PFS), confirmed overall response rate (ORR) by RECIST v1.1, disease control rate (DCR) (partial response or stable disease ≥ 16 weeks), and safety. Clinical variables associated with survival were explored using Cox proportional hazards stepwise regression analysis. Results: Of the 80 randomized patients, 40 received gemcitabine/nab-paclitaxel (GA) and 38 received gemcitabine/nab-paclitaxel/NPC-1C (GA+N) between April 2014 to March 2017. The median follow-up time was 5.8 months. Enrolled patients had a median age of 62 years (range, 36-78), 32 patients (41%) were female, and 4 patients (5%) had locally advanced disease. The trial was stopped early for futility following a pre-planned interim analysis, and patients were followed. The median OS in the GA arm was 6.6 months (95% confidence interval [CI]: 4.7-8.4) and 5.0 months (95% CI: 3.3-6.5; log-rank p=0.22) in the GA+N arm. The median PFS was 2.7 months (95% CI: 1.9-4.1) for GA and 3.4 months (95% CI: 1.9-5.3; log-rank p=0.80) for GA+N. The ORR (n=66) was 3% (95% CI: 0.4%-19%) for GA and 3% (95% CI: 0.4%-20%) for GA+N. The DCR was 23.5% (95% CI: 12.1%-40.8%) for GA and 28.1% (95% CI: 15.1%-46.2%) for GA+N (Fisher exact, p=0.78). There were minimal differences in toxicity between arms, except grade ≥ 3 anemia was more common in patients treated with GA+N vs. GA (39% vs 10%, Fisher exact, p=0.003). Chemotherapy dose reductions occurred in 69% of all patients at least one time (65% GA vs. 74% GA+N, Fisher exact, p=0.47). Decreased performance status, two or more metastatic sites, lymphocyte-to-monocyte ratio < 2.8, and CA19-9 > 2000 IU/mL were independently correlated with worse outcomes in the full study population. Conclusions: NPC-1C did not enhance the efficacy of gemcitabine and nab-paclitaxel. These data provide a benchmark for survival outcomes, dose modification patterns, and prognostic factors of patients treated with second-line gemcitabine and nab-paclitaxel.
Citation Format: Brandon M. Huffman, Atrayee Basu Mallick, Nora K. Horick, Andrea Wang-Gillam, Peter J. Hosein, Michael Morse, Muhammad Shaalan Beg, Janet E. Murphy, Benjamin L. Schlechter, Hanna Sanoff, Brian M. Wolpin, Philip Arlen, Jill Lacy, James M. Cleary. A multicenter randomized phase II study of gemcitabine and nab-paclitaxel versus gemcitabine and nab-paclitaxel with a MUC5AC antibody (NPC-1C) in advanced pancreatic cancer previously treated with FOLFIRINOX (NCT01834235) [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A019.