228P - Subgroup analysis by prior non-liposomal irinotecan therapy in NAPOLI-1: a phase 3 study of nal-IRI±5-fluorouracil/leucovorin in patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy

Abstract

Background: In the global, randomized phase 3 NAPOLI-1 study, liposomal irinotecan (nal-IRI) + 5-fluorouracil/leucovorin (5-FU/LV) significantly increased median OS vs. 5-FU/LV by 45% (6.1 vs. 4.2 mo; unstratified HR = 0.67 [0.49–0.92]; P = 0.012) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who have progressed following gemcitabine-based therapy. Here, we present a subgroup analysis by prior non-liposomal irinotecan (NLI). Methods: Study methodology has been published (Wang-Gillam; Lancet 2016). Robustness of overall treatment effect was assessed by prospectively-defined subgroups, including prior NLI, based on primary survival analysis data (cut-off February 2014) of the ITT population. Results: OS, PFS and CA19-9 response rates in patients with (n = 29) and without (n = 207) prior NLI are shown (see Table). In patients without prior NLI, nal-IRI+5-FU/LV (n = 105) improved median OS vs. 5-FU/LV (n = 102) by 2.5 mo to 6.7 mo (HR = 0.62; P < 0.01). Most frequent TEAEs were GI disorders (diarrhea, vomiting, nausea), regardless of prior NLI. ≥Grade 3 TEAEs and TEAEs leading to dose modification were similar in patients with (9 [75%]; 6 [50%]) and without (81 [77%]; 77 [73%]) prior NLI in the nal-IRI+5-FU/LV arm.Table: 228PPrior NLInal-IRI+5-FU/LV (n = 12 [10.3%])5-FU/LV (n = 17 [14.3%])Unstratified HR (95%CI); p-valueMedian OS, mo (95%CI)4.57 (0.99–6.44)4.83 (1.94–NR)1.25 (0.49–3.19); P=0.64Median PFS, mo (95%CI)1.51 (0.92–4.53)1.43 (1.18–4.40)0.83 (0.34–2.02); P=0.66CA19-9 response rates, n/N (%)0/10 (0)0/10 (0)N/ANo prior NLInal-IRI+5-FU/LV (n = 105 [89.7%])5-FU/LV (n = 102 [85.7%])Median OS, mo (95%CI)6.67 (5.26–8.97)4.17 (3.15–5.82)0.62 (0.44–0.86); P<0.01Median PFS, mo (95%CI)3.45 (2.76–4.24)1.48 (1.41–1.87)0.52 (0.37–0.71); P<0.0001CA19-9 response rates, n/N (%)28/87 (32.2)7/71 (9.9)P<0.001 Open table in a new tab Conclusions: This post-hoc subgroup analysis shows significant increases for nal-IRI+5-FU/LV vs. 5-FU/LV in OS, PFS and CA19-9 response rates in patients without prior NLI. Outcomes were similar in both arms in patients with prior NLI. The low number of patients with prior NLI preclude firm conclusions from being drawn and further research is needed to explore the impact of prior NLI. Clinical trial indentification: NCT01494506 Legal entity responsible for the study: This study was sponsored by Merrimack Pharmaceuticals, Inc., Cambridge, MA, USA; rights for nal-IRI now reside with Ipsen in the US (April 2017); PharmaEngine, Inc. holds the rights in Taiwan; Shire holds rights in the rest of the world through a licensing agreement with Ipsen. Funding: This study by Merrimack Pharmaceuticals, Inc., Cambridge, MA, USA; editorial assistance was funded by Shire (previously Baxalta), Zug, Switzerland. Disclosure: J.F. Blanc: Honoraria received from Bayer Sp, Merrimack; Consultant/Advisor for Bristol-Myers Squibb, Novartis, Lilly Oncology; Travel/Accommodation/Expenses received from Bayer Sp. R. Hubner: Consultant/Advisor for Celgene, BTG, Baxalta (now part of Shire); Speakers’ Bureau for Abbott, Ipsen; Travel/Accommodation/Expenses received from Celgene. A. Wang-Gillam: Consultant/Advisor for Merrimack, Pfizer, Newlink Genetics; Research funding from Newlink Genetics, AstraZeneca, BioMed Valley Discoveries, Lilly, AbbVie, Verastem, Precision Biologics. G. Bodoky: Honoraria received from Servier, Roche, Bayer, Pfizer, Janssen, Novartis, Lilly; Advisory boards for Bayer, Roche, Pfizer, Janssen, Novartis, Lilly, Taiho, Nordic. A. Dean: Honoraria received from Specialised Therapeutics Australia; Consultant/Advisor for Baxalta (now part of Shire), Celgene. G. Jameson: Honoria received from Celgene; Speakers’ Bureau for Celgene. D. Cunningham: Research funding from Amgen, AstraZeneca, Bayer, Celgene, Merrimack, Medimmune, Merck Serono, Sanofi. F. Braiteh: Relevant to this publication: Consultant fees received from Ipsen and Merrimack; Honoraria from Ipsen: Travel/Accommodation fees from Ipsen and Merrimack; Speaker’s Bureau for Ipsen and Merrimack. D. von Hoff: Relevant to this publication: Research funding from Merrimack; Consultant for Alphamed Consulting and Baxalta (now part of Shire). L-T. Chen: Consultant/Advisor for ONO, Eli Lilly, MSD, PharmaEngine, Merrimack, TTY Biopharm, SynCore Biotechnology, Five Prime Therapeutics, Novartis; Research funding from Novartis, GSK, Merck Serono, TTY Biopharm, Polaris; Patents/Royalties/Intellectual property with HuniLife Biotechnology. K. Mamlouk: Employment – Ipsen; former Merrimack employee Stock and Other Ownership Interests - Blueprint Medicines; Merrimack, F. de Jong: Shire employee and stockholder. J. Siveke: Consultant/advisor: Celgene, Merrimack, Baxalta, Boehringer-Ingelheim, Lilly; Honoraria: Celgene, Merrimack, Baxalta, Lilly; Research funding: Novartis, Boehringer-Ingelheim, Celgene, BMS. All other authors have declared no conflicts of interest.