Abstract B14: CA 19-9 levels in patients with metastatic pancreatic adenocarcinoma receiving first-line therapy with liposomal irinotecan plus 5-fluorouracil/leucovorin and oxaliplatin (NAPOX)
Authors: Dayyani Farshid , Boland Patrick M. , Dean Andrew , Lieu Christopher H. , Macarulla Teresa , Zhang Bin , Belanger Bruce , Moore Yan , Maxwell Fiona , Wang Tiffany , Wainberg Zev A. 
Published: March 2020

Abstract
Introduction: Liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) is approved for patients with metastatic pancreatic adenocarcinoma (mPAC) after disease progression following gemcitabine-based therapy. The combination of nal-IRI+5-FU/LV plus oxaliplatin (NAPOX) is being investigated as first-line treatment for patients with mPAC in a phase 1/2, open-label, dose exploration and dose expansion study (NCT02551991). This exploratory analysis investigated changes in carbohydrate antigen (CA) 19-9 levels, and their association with response rates, in patients with mPAC receiving NAPOX.
Methods: After establishing a recommended dose in the exploration phase of study NCT02551991 (nal-IRI 50 mg/m2 [free-base equivalent], oxaliplatin 60 mg/m2, LV 400 mg/m2, 5-FU 2400 mg/m2 on days 1 and 15 of each 28-day cycle), 25 patients were enrolled into the dose expansion phase, resulting in a total of 32 patients treated at the selected dose level (pooled population; PP). The data cut-off for this interim analysis was when all treated patients had completed at least 16 weeks of follow-up. CA 19-9 levels were assessed at baseline and up to week 16.
Results: Overall, 30 of the 32 treated patients in the PP had available CA 19-9 data at baseline. The median CA 19-9 level at baseline was 316 U/mL, with 23 (77%) patients having baseline CA 19-9 levels above the normal level (&gt;37 U/mL). Among patients with baseline CA 19-9 levels &gt;37 U/mL and measurements up to week 16 (n = 17), the median best reduction from baseline in CA 19-9 was 35.9%; a best CA 19-9 reduction of ≥20%, ≥50%, and ≥70% was achieved by 59% (10/17), 41% (7/17), and 24% (4/17) of patients, respectively. A total of 72% (23/32) treated patients achieved disease control by week 16 (DCR16), and the overall response rate (ORR; complete response or partial response over entire follow-up period) was 34% (11/32). In treated patients with any reduction in CA 19-9 by week 16, the DCR16 rate was 88% (14/16) and the ORR was 63% (10/16). Among patients with above-normal baseline CA 19-9 levels and any CA 19-9 reduction by week 16, the DCR16 rate was 83% (10/12) and the ORR was 67% (8/12). Rates of DCR16 and ORR increased with greater CA 19-9 reductions, reaching 100% and 75-83%, respectively, in patients with a CA 19-9 decrease of ≥70%.
Conclusion: In patients with mPAC, first-line NAPOX therapy (with a dosing schedule of nal-IRI 50 mg/m2, oxaliplatin 60 mg/m2, LV 400 mg/m2, and 5-FU 2400 mg/m2 on days 1 and 15 of each 28-day cycle) resulted in substantial reductions in CA 19-9 levels from baseline, indicative of antitumor activity. Response rates were higher in patients with greater CA 19-9 reductions. Further assessment of CA19-9 levels and response rates over a longer follow-up period is ongoing.
Citation Format: Farshid Dayyani, Patrick M. Boland, Andrew Dean, Christopher H. Lieu, Teresa Macarulla, Bin Zhang, Bruce Belanger, Yan Moore, Fiona Maxwell, Tiffany Wang, Zev A. Wainberg. CA 19-9 levels in patients with metastatic pancreatic adenocarcinoma receiving first-line therapy with liposomal irinotecan plus 5-fluorouracil/leucovorin and oxaliplatin (NAPOX) [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B14.