Second- or Later-Line Treatments for Advanced and Metastatic Gastric Cancer: A Network Meta-Analysis Comparing Treatments to Paclitaxel
Author(s)
Shikha Sharma, MSc MSc PhD1, David McConnell, BA, PhD2, Niamh Carey, BSc, MSc, PharmD, PhD3, Patrick Kearns, B. A (Hons.) MPH4, Jacintha O'Sullivan, PhD5, Maeve Lowery, MB BCh BAO6, Laura Mccullagh, BSc, PhD7.
1Trinity Translational Medicine Institute, Trinity College Dublin, National Centre for Pharmacoeconomics, Dublin, Ireland, 2National Centre for Pharmacoeconomics, Dublin 8, Ireland, 3National Centre for Pharmacoeconomics, DUBLIN 8, Ireland, 4Trinity College Dublin, National Centre for Pharmacoeconomics, Dublin 8, Republic of Ireland, Ireland, 5Trinity College Dublin, Dublin 8, Republic of Ireland, Ireland, 6St James's Hospital, Trinity College Dublin, Dublin 8, Republic of Ireland, Ireland, 7National Centre for Pharmacoeconomics, Trinity College Dublin, Dublin 8, Ireland.
1Trinity Translational Medicine Institute, Trinity College Dublin, National Centre for Pharmacoeconomics, Dublin, Ireland, 2National Centre for Pharmacoeconomics, Dublin 8, Ireland, 3National Centre for Pharmacoeconomics, DUBLIN 8, Ireland, 4Trinity College Dublin, National Centre for Pharmacoeconomics, Dublin 8, Republic of Ireland, Ireland, 5Trinity College Dublin, Dublin 8, Republic of Ireland, Ireland, 6St James's Hospital, Trinity College Dublin, Dublin 8, Republic of Ireland, Ireland, 7National Centre for Pharmacoeconomics, Trinity College Dublin, Dublin 8, Ireland.
OBJECTIVES: The treatment landscape for advanced and metastatic gastric cancer, in the second- and subsequent-line setting, is rapidly evolving. Uncertainty remains regarding the relative efficacy and safety of novel treatments. The study aimed to investigate the relative efficacy and safety of treatments (that are recommended by the National Comprehensive Cancer Network (NCCN), and the European Society for Medical Oncology (ESMO)) for this setting.
METHODS: Randomised controlled trials (RCTs) of relevant treatments (2009 to May 2024) were identified via a systemic search. Bayesian Network Meta-Analysis (NMA) was conducted for each outcome of interest (overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and Grade ≥ 3 treatment-related adverse events (TRAE)). All RCTs were assessed for eligibility for inclusion in evidence networks on the basis of outcomes reported, exchangeability and network connectivity. Forest plots were constructed to illustrate estimates of relative efficacy and safety of each treatment compared to the benchmark comparator, paclitaxel. Analyses were in R (4.4.2) and JAGS (4.3.1) using BUGSnet.
RESULTS: We identified 44 RCTs of relevant treatments. NMAs were feasible for treatments in the second-line setting only, with a total of 10 studies included in the analyses. No statistically significant differences in efficacy between treatments were detected. Compared to paclitaxel, both best supportive care and ramucirumab were associated with numerically higher OS event-risk, pembrolizumab with numerically higher PFS event-risk, and paclitaxel in combination with ramucirumab with numerically higher ORR. Versus paclitaxel, pembrolizumab was associated with a significant decreased risk of Grade ≥ 3 TRAE; both irinotecan and FOLFIRI were associated with numerically higher risk of Grade ≥ 3 TRAE.
CONCLUSIONS: The treatment landscape here is rapidly evolving. Our work indicates that there remains a need for novel treatments, in this setting, that will be associated with significant benefits in relative efficacy and safety versus more established treatments.
METHODS: Randomised controlled trials (RCTs) of relevant treatments (2009 to May 2024) were identified via a systemic search. Bayesian Network Meta-Analysis (NMA) was conducted for each outcome of interest (overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and Grade ≥ 3 treatment-related adverse events (TRAE)). All RCTs were assessed for eligibility for inclusion in evidence networks on the basis of outcomes reported, exchangeability and network connectivity. Forest plots were constructed to illustrate estimates of relative efficacy and safety of each treatment compared to the benchmark comparator, paclitaxel. Analyses were in R (4.4.2) and JAGS (4.3.1) using BUGSnet.
RESULTS: We identified 44 RCTs of relevant treatments. NMAs were feasible for treatments in the second-line setting only, with a total of 10 studies included in the analyses. No statistically significant differences in efficacy between treatments were detected. Compared to paclitaxel, both best supportive care and ramucirumab were associated with numerically higher OS event-risk, pembrolizumab with numerically higher PFS event-risk, and paclitaxel in combination with ramucirumab with numerically higher ORR. Versus paclitaxel, pembrolizumab was associated with a significant decreased risk of Grade ≥ 3 TRAE; both irinotecan and FOLFIRI were associated with numerically higher risk of Grade ≥ 3 TRAE.
CONCLUSIONS: The treatment landscape here is rapidly evolving. Our work indicates that there remains a need for novel treatments, in this setting, that will be associated with significant benefits in relative efficacy and safety versus more established treatments.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
MSR184
Topic
Clinical Outcomes, Health Policy & Regulatory, Methodological & Statistical Research
Disease
Gastrointestinal Disorders, No Additional Disease & Conditions/Specialized Treatment Areas, Oncology, Personalized & Precision Medicine