A SYSTEMATIC LITERATURE REVIEW (SLR) AND INDIRECT TREATMENT COMPARISON (ITC) FEASIBILITY ASSESSMENT OF THE COMPARATIVE EFFICACY OF TREATMENTS IN HER2+, RAS WILD-TYPE (WT), METASTATIC COLORECTAL CANCER (MCRC)
Author(s)
Sheena Thakkar, BS, MPH1, Joseph C. Cappelleri, MPH, MS, PhD2, Haitao Chu, PhD, MD3, Liza Takiya, PharmD4, Julie C. Reid, BSc, MSc, PhD5, Nikita Sir, BSc5, Yashika Bhalla, PhD6, Imtiaz A. Samjoo, BSc, MSc, PhD5.
1Pfizer Inc., Acton, MA, USA, 2Pfizer, Newington, CT, USA, 3Pfizer, Edina, MN, USA, 4Pfizer Inc., New York, NY, USA, 5EVERSANA, Victoria, BC, Canada, 6EVERSANA, Pune, India.
1Pfizer Inc., Acton, MA, USA, 2Pfizer, Newington, CT, USA, 3Pfizer, Edina, MN, USA, 4Pfizer Inc., New York, NY, USA, 5EVERSANA, Victoria, BC, Canada, 6EVERSANA, Pune, India.
OBJECTIVES: HER2+, RAS WT mCRC is a clinically meaningful subgroup, occurring in approximately 2-6% of metastatic cases. Several targeted therapies have shown promising anti-tumor activity, leading to specific treatment recommendations. Direct evaluation of all treatment options via randomized controlled trials (RCTs) is rarely feasible; therefore, ITCs can support comparative assessment when trials are sufficiently comparable. Feasibility assessment is essential to evaluate cross‑trial comparability. We summarize findings from an SLR and ITC feasibility assessment of RCTs in HER2+, RAS WT mCRC.
METHODS: An SLR was conducted to identify trials evaluating therapies for HER2+, RAS WT mCRC. Searches were conducted in Ovid® databases from inception to September 2025 and supplemented with grey literature (PROSPERO: CRD420251163361). Identified RCTs were assessed for ITC feasibility based on comparability of treatments, outcomes, study design, and patient characteristics.
RESULTS: Nine RCTs were included. Trials varied by phase (five phase II, four phase III), duration (10-61 months), sample size (53-823), geographic scope, HER2 eligibility criteria, and allowable prior therapies. The proportion of HER2+/RAS WT patients ranged from 5% to 100%. All trials reported efficacy outcomes, but definitions and time points were inconsistent. No two trials evaluated identical treatment doses or schedules, preventing a full network meta-analysis (NMA) inclusive of all 9 RCTs. A small 2-study network linked experimental treatments to bevacizumab + fluorouracil-based chemotherapy. Overall, treatment heterogeneity reflects the lack of standard of care for this population.
CONCLUSIONS: Marked heterogeneity in study populations, designs, outcomes, and limited network connectivity limits feasibility of standard ITCs. Population-adjusted ITCs using individual patient data may serve as a methodological alternative. Greater harmonization of trial designs, eligibility criteria, and outcome measures will be critical to more robust comparative analyses for HER2+, RAS WT mCRC moving forward.
METHODS: An SLR was conducted to identify trials evaluating therapies for HER2+, RAS WT mCRC. Searches were conducted in Ovid® databases from inception to September 2025 and supplemented with grey literature (PROSPERO: CRD420251163361). Identified RCTs were assessed for ITC feasibility based on comparability of treatments, outcomes, study design, and patient characteristics.
RESULTS: Nine RCTs were included. Trials varied by phase (five phase II, four phase III), duration (10-61 months), sample size (53-823), geographic scope, HER2 eligibility criteria, and allowable prior therapies. The proportion of HER2+/RAS WT patients ranged from 5% to 100%. All trials reported efficacy outcomes, but definitions and time points were inconsistent. No two trials evaluated identical treatment doses or schedules, preventing a full network meta-analysis (NMA) inclusive of all 9 RCTs. A small 2-study network linked experimental treatments to bevacizumab + fluorouracil-based chemotherapy. Overall, treatment heterogeneity reflects the lack of standard of care for this population.
CONCLUSIONS: Marked heterogeneity in study populations, designs, outcomes, and limited network connectivity limits feasibility of standard ITCs. Population-adjusted ITCs using individual patient data may serve as a methodological alternative. Greater harmonization of trial designs, eligibility criteria, and outcome measures will be critical to more robust comparative analyses for HER2+, RAS WT mCRC moving forward.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
SA75
Topic
Study Approaches
Topic Subcategory
Literature Review & Synthesis
Disease
Oncology