Abstract 324P
Background
NAPOLI 3, a global, randomized, phase 3 study, demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) for NALIRIFOX vs gemcitabine+nab-Paclitaxel (Gem+NabP) in pts with mPAC. The aim of this post-hoc analysis is to evaluate the effects of NALIRIFOX in the Asian subgroup (AG) of NAPOLI 3.
Methods
In the NAPOLI 3 the pts had a confirmed PAC not previously treated in the metastatic setting and with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0/1. They were randomized to NALIRIFOX (liposomal irinotecan 50 mg/m2+ 5-FU 2400 mg/m2 + leucovorin 400 mg/m2+ oxaliplatin 60 mg/m2 on days 1 and 15 of a 28-day cycle) or Gem+NabP (Gem 1000 mg/m2 + NabP 125 mg/m2 on days 1, 8, and 15 of a 28-day cycle). Primary endpoint was OS. Secondary endpoints included PFS, ORR and safety; 383 pts were randomized to NALIRIFOX and 387 to Gem+NabP. Median follow-up was 16.1 months (mts).
Results
38 Asian pts (mean age 60.3 years; 60.5% male) were enrolled from Korean and non-Asian sites. Baseline characteristics were balanced between the two treatment arms; Asian pts had a worse ECOG PS and a lower CA 19.9 level vs the general population (GP). In the AG, NALIRIFOX significantly prolonged OS vs Gem+NabP (hazard ratio [HR] 0.31; 95% CI 0.10-0.98). The median OS in NALIRIFOX arm was 14.5 mts in the AG and 11.1 mts in the GP. PFS was also prolonged vs Gem+NabP (HR 0.59; 95% CI 0.21–1.60). The median PFS in NALIRIFOX arm was 10 mts in the AG and 7.4 mts in the GP. In the AG, ORR rate was 70% in NALIRIFOX arm and 41.8% in the GP. In the AG, the incidence of grade ≥3 adverse events (≥G3 AEs) in NALIRIFOX arm was 50% and was 62.2% in the GP. In NALIRIFOX arm, the AG had more ≥G3 hematological events than the GP (40% vs 33%) and fewer ≥G3 non-hematological events in the NALIRIFOX arm than the GP (20.0% vs 42.2%) including ≥G3 diarrhea (5% vs 20.3%).
Conclusions
The effect of NALIRIFOX in AG was consistent with the GP of NAPOLI 3. NALIRIFOX had a manageable safety profile with a slightly higher incidence of severe hematological events and lower incidence of severe diarrhea.
Clinical trial identification
NCT04083235.
Legal entity responsible for the study
Ipsen Servier.
Funding
Ipsen.
Disclosure
T. Macarulla Mercade: Financial Interests, Personal, Advisory Board: Ability Pharmaceutical, SL, AstraZeneca, Basilea Pharma, Batxer, BioLineRX Ltd., Celgene SLU, Eisai, Ipsen Pharma, Incyte; Financial Interests, Personal, Other, Direct research fund: Servier, Merck, Sharp and Dohme, Novocure, QED Therapeutics Inc, Roche, Sanofi-Aventis, Zymeworks; Financial Interests, Personal, Invited Speaker: Lilly, Janssen; Financial Interests, Institutional, Research Grant: Amc Medical Research, Armo Biosciences, Basilea, Biokeralty Research Institute, Merck Sharp & Dohme, Oncomed Pharmaceuticals, QED Therapeutics, VCN Biosciences, AbbVie Farmaceútica, Ability Pharmaceuticals, Agios, Amgen, Aslan, AstraZeneca, Bayer, BeiGene, Biolinerx, Blueprint Medicines, Boston Biomedical, Bristol Myers Squibb (BMS), Cantargia, Celgene, Eisai, Erytech Pharma, F. Hoffmann-la Roche, FibroGen, Genentech, Hallozyme, Immunomedics, Incyte, Ipsen, Lab. Menarini, Lilly, Loxo Oncology, MedImmune, Merimarck, Millenim, Nelum, Novartis, Novocure, Pfizer, Pharmacyclics, Roche, Zymeworks; Non-Financial Interests, Member: American Society of Clinical Oncology - ASCO, “Sociedad Española de Oncología Médica” – SEOM, Sociedad Europea de Oncología Médica - ESMO; Other, Editorial Board: GI Annals og¡f Oncology. A. Bullock: Financial Interests, Personal, Advisory Board: Agenus, Sirtex, Merck; Financial Interests, Institutional, Invited Speaker: Seagen, Agenus, AstraZeneca, Geistlich, Panova, Ipsen. A.S. Paulson: Financial Interests, Personal, Full or part-time Employment: Day One Biopharmaceuticals; Financial Interests, Personal, Ownership Interest: Actinium; Financial Interests, Personal, Other, honoraria: Cardinal Health, Curio Science, Array BioPharma; Financial Interests, Personal, Advisory Role: Amgen, Bristol Myers, Eisai, Ipsen, Advanced Accelerator Applications, Incyte, Exelixis, Pfizer, QED Therapeutics, Lilly Pharmaceuticals, Mirati, Hutchinson, Astellas Pharma, AADi, Stromatis Pharma, EMD Serono, AstraZeneca, Servier, Novartis, Array BioPharma, Bayer, Jazz Pharmaceuticals, Takeda, Seagen, Agenus; Financial Interests, Personal, Speaker’s Bureau: Ideo Oncology; Financial Interests, Personal, Other, travel, accommodation, expenses: Pfizer, Camurus, Mirati, Nucana, AADi; Financial Interests, Personal, Research Grant: Buzzard Pharmaceuticals; Financial Interests, Institutional, Research Grant: Ipsen, Bristol Myers Squibb, Exelixis, Hutchinson, Taiho Pharmaceutical, Lilly, AstraZeneca, Incyte, Deciphera, G1 Therapeutics, Zentallis, Tempus, Camurus, Relay Therapeutics, Nucana, Merck, Bayer, Seattle Genetics, Sotio, Innovative Cellular Therapeutics Co, Regenxbio, Gilead Sciences, Gritstone Bio, BioNTech SE, Novartis, TransThera Biosciences, ITM Oncologics, Inspirna. J. Peguero: Financial Interests, Personal, Full or part-time Employment: Oncology Consultants; Financial Interests, Personal, Leadership Role: Oncology Consultants; Financial Interests, Personal, Stocks/Shares: Oncology Consultants, Roche, Spectrum Pharmaceuticals, Tersera, Zogen; Financial Interests, Personal, Advisory Role: Tersera; Financial Interests, Personal, Speaker’s Bureau: Agendia; Guardant Health; Tempus; Financial Interests, Personal, Other, travel, accommodation, expenses: Agendia; Guardant Health; Tempus; Financial Interests, Personal, Research Grant: AbbVie (Inst); Amgen (Inst); Astellas Pharma (Inst); Bavarian Nordic (Inst); BerGenBio (Inst); Boehringer Ingelheim (Inst); Calithera Biosciences (Inst); Dizal Pharma (Inst); eFFECTOR Therapeutics (Inst); EMD Serono (Inst); Epizyme (Inst); Genentech/Roche. H. Hassan: Financial Interests, Personal, Full or part-time Employment: Servier. F. Delaporte: Financial Interests, Personal, Full or part-time Employment: Servier. L. Martin Fernandez: Financial Interests, Personal, Full or part-time Employment: Servier. N. Causse-Amellal: Financial Interests, Personal, Full or part-time Employment: Servier. D. Melisi: Financial Interests, Personal, Advisory Board: Incyte co., Servier, iOnctura, Tahio; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Research Grant: iOnctura. All other authors have declared no conflicts of interest.