Comparative Efficacy of First-Line Chemotherapies for Metastatic Pancreatic Cancer (mPC) Using Bayesian Network Meta-Analysis (Nma) of Survival Curves
Author(s)
Roselyn S. Amamoo, MPH1, Rosemond S. Amamoo, MPH1, Brian Erstad, PharmD2, Celina I. Valencia, DrPH3, Ivo Abraham, PhD1.
1Health and Pharmaceutical Outcomes, University of Arizona College of Pharmacy, Tucson, AZ, USA, 2University of Arizona College of Pharmacy, Tucson, AZ, USA, 3University of Arizona, Tucson, AZ, USA.
1Health and Pharmaceutical Outcomes, University of Arizona College of Pharmacy, Tucson, AZ, USA, 2University of Arizona College of Pharmacy, Tucson, AZ, USA, 3University of Arizona, Tucson, AZ, USA.
Presentation Documents
OBJECTIVES: The NAPOLI 3 trial added NALIRIFOX as a new first-line treatment option for mPC to the existing options of FOLFIRINOX, Nab-paclitaxel plus gemcitabine (NABP+GEM) and Gemcitabine (GEM). In contrast to conventional NMA using hazard ratios (HR), we applied an innovative method using reconstructed pseudo individual patient-level data (IPD) from published survival curves without the constraint of the proportional hazards assumption to conduct a Bayesian indirect treatment comparison of these regimens.
METHODS: Eligible phase III randomized clinical trials directly comparing either NALIRIFOX, FOLFIRINOX, NABP+GEM or GEM were identified from PubMed and Embase. The pseudo-IPD were reconstructed using the Liu et al method. A Bayesian NMA was conducted using overall survival (OS) and progression free-survival (PFS) curves to estimate the HRs over a time frame of 1 month to 36 months, with the assumption that the true survival functions follow parametric distributions such as Weibull, Gompertz, Exponential, Log-logistic, and Log-normal. The best-fitting model was selected based on the lowest deviance information criterion (DIC). Fixed effects log-logistic and log-normal models were retained for OS and PFS curves, respectively, with NALIRIFOX as the comparator.
RESULTS: For OS, the HRs of FOLFIRINOX at months 1 and 36 were 1.06 (95%CrI=1.05-1.08) and 1.10 (95%CrI=1.08-1.12), respectively. The corresponding estimates for NABP+GEM were 1.17 (95%CrI=1.10-1.24) and 1.13 (95%CrI=1.05-1.24); and 1.50 (95%CrI=1.24-1.82) and 1.31 (95%CrI=1.05-1.67) for GEM. For PFS, the HRs of FOLFIRINOX at months 1 and 36 were 1.12 (95%CrI=1.09-1.14) and 1.28 (95%CrI=1.25-1.32). Corresponding estimates for NABP+GEM were 1.36 (95%CrI=1.29-1.41) and 1.52 (95%CrI=1.39-1.66); and 2.00 (95%CrI=1.63-2.42) and 2.25 (95%CrI=1.63-3.12) for GEM.
CONCLUSIONS: This Bayesian NMA of survival curves for mPC indicates FOLFIRINOX and NALIRIFOX have comparable survival benefits, both associated with peripheral neuropathy and hematological toxicity, with NALIRIFOX being comparably more tolerable. NABP+GEM is a suitable option for patients with lower performance status. All three regimens prevailed in efficacy over GEM.
METHODS: Eligible phase III randomized clinical trials directly comparing either NALIRIFOX, FOLFIRINOX, NABP+GEM or GEM were identified from PubMed and Embase. The pseudo-IPD were reconstructed using the Liu et al method. A Bayesian NMA was conducted using overall survival (OS) and progression free-survival (PFS) curves to estimate the HRs over a time frame of 1 month to 36 months, with the assumption that the true survival functions follow parametric distributions such as Weibull, Gompertz, Exponential, Log-logistic, and Log-normal. The best-fitting model was selected based on the lowest deviance information criterion (DIC). Fixed effects log-logistic and log-normal models were retained for OS and PFS curves, respectively, with NALIRIFOX as the comparator.
RESULTS: For OS, the HRs of FOLFIRINOX at months 1 and 36 were 1.06 (95%CrI=1.05-1.08) and 1.10 (95%CrI=1.08-1.12), respectively. The corresponding estimates for NABP+GEM were 1.17 (95%CrI=1.10-1.24) and 1.13 (95%CrI=1.05-1.24); and 1.50 (95%CrI=1.24-1.82) and 1.31 (95%CrI=1.05-1.67) for GEM. For PFS, the HRs of FOLFIRINOX at months 1 and 36 were 1.12 (95%CrI=1.09-1.14) and 1.28 (95%CrI=1.25-1.32). Corresponding estimates for NABP+GEM were 1.36 (95%CrI=1.29-1.41) and 1.52 (95%CrI=1.39-1.66); and 2.00 (95%CrI=1.63-2.42) and 2.25 (95%CrI=1.63-3.12) for GEM.
CONCLUSIONS: This Bayesian NMA of survival curves for mPC indicates FOLFIRINOX and NALIRIFOX have comparable survival benefits, both associated with peripheral neuropathy and hematological toxicity, with NALIRIFOX being comparably more tolerable. NABP+GEM is a suitable option for patients with lower performance status. All three regimens prevailed in efficacy over GEM.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO157
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
SDC: Neurological Disorders, SDC: Oncology