Oral Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2023

NAPOLI-3: A randomized, open-label phase 3 study of NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naïve patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) (#101)

Andrew Dean 1 , Davide Melisi 2 , Teresa Macarulla 3 , Roberto A Pazo Cid 4 , Sreenivasa R Chandana 5 , Christelle De La Fouchardière 6 , Igor Kiss 7 , Woojin Lee 8 , Thorsten O Goetze 9 , Eric Van Cutsem 10 , Scott Paulson 11 , Tanios Bekaii-Saab 12 , Shubham Pant 13 , Richard Hubner 14 , Zhimin Xiao 15 , Huanyu Chen 15 , Fawzi Benzaghou 15 , Zev A Wainberg 16 , Eileen M O'Reilly 17
  1. St John of God Subiaco Hospital, Subiaco, Australia
  2. Invesitigational Cancer Therapeutics Clinical Unit, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
  3. Vall d'Hebron University Hospital, Barcelona, Spain
  4. Hospital Universitario Miguel Servet, Zaragoza, Spain
  5. Cancer and Hematology Centers of Western Michigan, Grand Rapids, Michigan, USA
  6. Centre Léon Bérard, Lyon, France
  7. Masaryk Memorial Cancer Institute and Faculty of Medicine, Masaryk University, Brno, Czechia
  8. National Cancer Center, Goyang, Republic of Korea
  9. Krankenhaus Nordwest, Frankfurt, Germany
  10. University Hospitals Gasthuisberg and KULeuven, Leuven, Belgium
  11. Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, Texas, USA
  12. Mayo Clinic, Scottsdale, AZ, USA
  13. MD Anderson Cancer Center, Houston, Texas, USA
  14. The Christie NHS Foundation Trust, Manchester, UK
  15. Ipsen, Cambridge, MA, USA
  16. University of California, Los Angeles, CA, USA
  17. Memorial Sloan Kettering Cancer Center, New York, USA

Aims: NAPOLI 3 (NCT04083235) investigated the efficacy and safety of liposomal irinotecan 50 mg/m2, 5-fluorouracil 2400 mg/m2, leucovorin 400 mg/m2 and oxaliplatin 60 mg/m2 (NALIRIFOX) versus nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 (Gem+NabP) as first-line therapy in patients with mPDAC.

Methods: Eligible patients with confirmed untreated mPDAC were randomized to receive NALIRIFOX on days 1 and 15 of a 28-day cycle or Gem+NabP on days 1, 8 and 15 of a 28-day cycle. The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), overall response rate (ORR) and safety. OS was evaluated when at least 543 events were observed using a stratified log-rank test with an overall one-sided significance level of 0.025.

Results: Overall, 770 patients (NALIRIFOX, n=383; Gem+NabP, n=387) were included. Baseline characteristics were balanced between arms. At a median follow-up of 16.1 months, 544 events had occurred. Median OS was 11.1 versus 9.2 months in the NALIRIFOX and Gem+NabP groups respectively; median PFS was 7.4 versus 5.6 months (Table). Grade 3/4 treatment-emergent adverse events occurring in ≥10% of patients receiving NALIRIFOX versus Gem+NabP included diarrhea (20.3% vs 4.5%), nausea (11.9% vs 2.6%), hypokalemia (15.1% vs 4.0%), anemia (10.5% vs 17.4%) and neutropenia (14.1% vs 24.5%).

 

 

NALIRIFOX
(n=383)

Gem+NabP
(n=387)

OS, months, median (95% CI)

 

11.1 (10.0–12.1)

9.2 (8.3–10.6)

HR (95% CI); p-value

 

0.83 (0.70–0.99); 0.04

 

OS rate, %

12 months

45.6

39.5  

 

18 months

26.2  

19.3  

PFS, months, median (95% CI)

 

7.4 (6.0–7.7)

5.6 (5.3–5.8)

HR (95% CI); p-value

 

0.69 (0.58–0.83); <0.0001

 

PFS rate, %  

12 months

27.4  

13.9  

 

18 months

11.4  

3.6  

ORR, % (95% CI)

 

41.8 (36.8–46.9)

36.2 (31.4–41.2)
         

Conclusions: First-line NALIRIFOX demonstrated clinically meaningful and statistically significant improvement in OS and PFS versus Gem+NabP in patients with mPDAC, with no new safety concerns.

Key words: metastatic pancreatic ductal adenocarcinoma; first-line; NALIRIFOX; liposomal irinotecan; survival rate

Funding: Funded by Ipsen.