221PD Efficacy and safety of nanoliposomal irinotecan (nal-IRI, MM-398, PEP02, BAX-2398) in patients with metastatic pancreatic cancer in Asia: A subgroup analysis of the phase 3 NAPOLI-1 Study

Background The global Phase 3 trial, NAPOLI-1, demonstrated that nal-IRIþ 5-fluorouracil and leucovorin (5-FU/LV) significantly improved overall (OS), progression-free survival (PFS) and objective response rate (ORR) vs 5-FU/LV in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPAC) previously treated with gemcitabine-based therapy. Herein, we present a post hoc subgroup analysis of the Asia cohort in the NAPOLI-1 study. Methods Pts were randomly assigned (1:1:1) to receive nal-IRI (80 mg/m2, equivalent to 70 mg/m2 of irinotecan base)þ 5-FU/LV (2400/400 mg/m2) q2w, nal-IRI (120 mg/m2, equivalent to 100 mg/m2 of irinotecan base) q3w, or 5-FU/LV (2000/200 mg/m2 weekly for weeks 1-4 q6w). The primary endpoint was OS. Results: Of 132 pts randomized in Asian centers, 34 were assigned to treatment with nal-IRIþ5-FU/LV, 50 with nal-IRI, and 48 with 5-FU/LV. In the Asia cohort, nal-IRIþ5-FU/LV significantly improved median OS versus 5-FU/LV (8.9 vs 3.7 months, P¼0.0281) (Table). Improvements in PFS and ORR were also observed. There were no significant differences in outcomes between 5-FU/LV and nal-IRI monotherapy. Grade _3 treatment-emergent adverse events in_15% of pts in either nal-IRI arm were neutropenia (55%, 34%, and 2% in the nal-IRIþ5-FU/LV, nal-IRI, and 5-FU/LV arms, respectively), white blood cell count decreased (21%, 8%, 0%), diarrhea (3%, 16%, 5%), and anemia (18%, 24%, 14%). There were no cases of Grade_3 peripheral neuropathy. Conclusions This subgroup analysis confirmed that nal-IRIþ5-FU/LV is an efficacious treatment option with a manageable safety profile in patients with mPAC treated in Asia. Nal-IRIþ5-FU/LV may represent a new standard of care for patients with mPAC previously treated with gemcitabine-based therapy. Clinical trial indentification: NCT01494506. Legal entity responsible for the study: Merrimack Funding: Merrimack Disclosure: L-T. Chen: Received data monitoring board, statistician, and support of medical writer from Merirmack, and honorarium from PharmaEngine, Inc. F. de Jong: Employee of and hold stock in Shire. M. Pipas: Employee of and hold stock in Merrimack. B. Belanger: Employee of, hold stock in, and have received reimbursement for travel/accommodations/expenses from Merrimack. E. Wang: Employee ofTabled 1Table: 221PDSummary of Treatment EfficacyEnd PointNal-IRI 1 5-FU/LV (N 534)5-FU/LV Combo Control (N 535)HR (95% CI)*P value’Nal-IRI (N5 50)5-FU/LVMonoControl(N 5 48)HR (95% CI)*P value’OS, months, median (95% CI)8.9 (4.4, 10.4)3.7 (2.7, 6.4)0.5087 (0.28, 0.93)0.02815.7 (4.8, 7.4)4.3 (3.1, 5.7)0.8339 (0.53, 1.3)0.4263PFS, months, median (95% CI)4.0 (1.5, 5.7)1.4 (1.2, 2.0)0.4818 (0.27, 0.85)0.01162.8 (1.5, 4.1)1.4 (1.3, 1.9)0.6874 (0.44, 1.1)0.0950ORR, %8.8%0%8.8 (-0.1, 18.4)0.114210.0%0%10.0 (1.7, 18.3)0.0564*Values reported for ORR represent a difference in proportions rather than a HR, and the CI limits for the difference in ORR are based on approximation.P value is based on Fisher exact test. P values are 2-sided.normal Open table in a new tab PharmaEngine, Inc. The company has the licensing partnership with Merrimack Pharmaceuticals for the product. Y-J. Bang: Consultant for Merrimack. All other authors have declared no conflicts of interest.