EPIDEMIOLOGY, PROGNOSIS, AND HEALTH-RELATED QUALITY OF LIFE (HRQOL) IN HER2-POSITIVE, RAS WILD-TYPE (WT), METASTATIC COLORECTAL CANCER (MCRC): A LITERATURE REVIEW AND QUALITATIVE SYNTHESIS
Author(s)
Sheena Thakkar, BS, MPH1, Joseph C. Cappelleri, MPH, MS, PhD2, Haitao Chu, PhD, MD3, Liza Takiya, PharmD4, Julie C. Reid, PhD5, Nikita Sir, BHSc5, Yashika Bhalla, PhD6, Imtiaz Samjoo, BSc, MSc, PhD7.
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, 7EVERSANA, Burlington, ON, Canada.
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, 7EVERSANA, Burlington, ON, Canada.
OBJECTIVES: CRC is the third most diagnosed malignancy and second leading cause of cancer-related mortality globally. HER2-positive/RAS WT mCRC represents a biomarker-defined subgroup underrepresented in research. This review aims to assess the proportion of HER2 and RAS genotypes, testing practices, biomarker-specific prognostic implications, and treatment impact on patients’ HRQoL in mCRC.
METHODS: A targeted literature review (TLR) of epidemiology and a HRQoL systematic literature review (SLR) were conducted in accordance with PRISMA guidelines. Electronic database searches (MEDLINE®, Embase, CENTRAL) were conducted from inception to October 2025. Grey literature (conference proceedings, trial registries) and cited references were reviewed. Eligible studies reported proportion of HER2 and RAS biomarkers, prognostic, or HRQoL outcomes in HER2-positive/RAS WT mCRC. Findings were synthesized qualitatively.
RESULTS: Eighty-seven studies (n=43,783 patients) were included in the TLR, including two comprising the HRQoL SLR. In studies evaluating HER2-positive/RAS WT mCRC patients, HER2-positivity (immunohistochemistry [IHC] 3+ or 2+ with in situ hybridization [ISH] amplification; n=34 studies; 20,330 patients) ranged from 0.7%—100%, with RAS WT (n=72 studies; 31,163 patients) from 1.5%—100%, and co-occurring HER2-positive/RAS WT (n=61 studies; 20,228 patients) from 2.2%—100%. HER2 testing was primarily via IHC with confirmatory ISH. Four studies compared HER2-positive/RAS WT (n=143) vs. HER2-negative/RAS WT (n=1,652), and reported outcomes across line-agnostic regimens (anti-EGFR, anti-VEGF, and HER2-targeted). Median overall survival (OS) ranged from 20—34 vs. 34—40 months and progression-free survival from 2—11 vs. 1—13 months in HER2-positive/RAS WT vs. HER2-negative/RAS WT patients, respectively. Two trials reported HRQoL outcomes using the EORTC QLC-C30; both demonstrated stable global HRQoL over time with HER2-targeted therapies.
CONCLUSIONS: Epidemiological estimates and outcomes in line-agnostic HER2-positive/RAS WT mCRC were variable due to selected populations, and inconsistent testing and reporting. Limited evidence suggests HRQoL is maintained with HER2-targeted treatments; however, further research is needed on patient-centered outcomes and standardized biomarker definitions.
METHODS: A targeted literature review (TLR) of epidemiology and a HRQoL systematic literature review (SLR) were conducted in accordance with PRISMA guidelines. Electronic database searches (MEDLINE®, Embase, CENTRAL) were conducted from inception to October 2025. Grey literature (conference proceedings, trial registries) and cited references were reviewed. Eligible studies reported proportion of HER2 and RAS biomarkers, prognostic, or HRQoL outcomes in HER2-positive/RAS WT mCRC. Findings were synthesized qualitatively.
RESULTS: Eighty-seven studies (n=43,783 patients) were included in the TLR, including two comprising the HRQoL SLR. In studies evaluating HER2-positive/RAS WT mCRC patients, HER2-positivity (immunohistochemistry [IHC] 3+ or 2+ with in situ hybridization [ISH] amplification; n=34 studies; 20,330 patients) ranged from 0.7%—100%, with RAS WT (n=72 studies; 31,163 patients) from 1.5%—100%, and co-occurring HER2-positive/RAS WT (n=61 studies; 20,228 patients) from 2.2%—100%. HER2 testing was primarily via IHC with confirmatory ISH. Four studies compared HER2-positive/RAS WT (n=143) vs. HER2-negative/RAS WT (n=1,652), and reported outcomes across line-agnostic regimens (anti-EGFR, anti-VEGF, and HER2-targeted). Median overall survival (OS) ranged from 20—34 vs. 34—40 months and progression-free survival from 2—11 vs. 1—13 months in HER2-positive/RAS WT vs. HER2-negative/RAS WT patients, respectively. Two trials reported HRQoL outcomes using the EORTC QLC-C30; both demonstrated stable global HRQoL over time with HER2-targeted therapies.
CONCLUSIONS: Epidemiological estimates and outcomes in line-agnostic HER2-positive/RAS WT mCRC were variable due to selected populations, and inconsistent testing and reporting. Limited evidence suggests HRQoL is maintained with HER2-targeted treatments; however, further research is needed on patient-centered outcomes and standardized biomarker definitions.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
SA97
Topic
Study Approaches
Topic Subcategory
Literature Review & Synthesis
Disease
Oncology