PROGNOSTIC IMPACT OF RAS/KRAS MUTATION STATUS ON SURVIVAL OUTCOMES IN FIRST-LINE METASTATIC COLORECTAL CANCER: A SYSTEMATIC LITERATURE REVIEW
Author(s)
Ihtisham Sultan, PhD1, Nadia Karim, MSc2, Caroline Barwood, MSc3, Alisha Gadhia, MSc4, Lavanya Garg, MSc4, Grace Newman, MSc4, Ines Bouajila, MSc4, Björn Stollenwerk, PhD5.
1Amgen Inc., Thousand Oaks, CA, USA, 2AMGEN, Crawley, United Kingdom, 3Acumetis, London, United Kingdom, 4Acumetisglobal, London, United Kingdom, 5Amgen (Europe) GmbH, Rotkreuz, Switzerland.
1Amgen Inc., Thousand Oaks, CA, USA, 2AMGEN, Crawley, United Kingdom, 3Acumetis, London, United Kingdom, 4Acumetisglobal, London, United Kingdom, 5Amgen (Europe) GmbH, Rotkreuz, Switzerland.
OBJECTIVES: The prognostic impact of Rat sarcoma (RAS) and Kirsten rat sarcoma (KRAS) mutations in first-line (1L) metastatic colorectal cancer (mCRC) remains uncertain, with studies reporting inconsistent survival outcomes. We conducted a systematic literature review (SLR) to evaluate progression-free survival (PFS) and overall survival (OS) outcomes associated with RAS/KRAS-mutated versus wild-type disease in 1L mCRC.
METHODS: A systematic search of Embase, Cochrane Library, and google scholar was conducted through October 15, 2025, supplemented by manual searches of conference proceedings from the two years preceding the search date. Eligible publications included randomized controlled trials (RCTs) and non-randomized studies evaluating first-line treatment outcomes in patients with RAS/KRAS-mutated mCRC. Of 2,629 records identified, 79 publications (48 RCTs and 31 non-RCTs) were included in the SLR. Of these, five publications evaluating the independent prognostic impact of RAS/KRAS mutations relative to wild-type disease were prioritized for this analysis. PFS and OS outcomes were extracted and summarized descriptively.
RESULTS: Across included studies, findings were mixed; however, a directional trend toward poorer survival outcomes among RAS/KRAS-mutated patients was observed. In studies reporting statistically significant differences, RAS/KRAS mutations were associated with a 36%-47% higher risk of progression and a 24%-60% higher risk of mortality versus wild-type disease. Although the magnitude of the association varied across studies, no study demonstrated a statistically significant survival advantage for RAS/KRAS-mutated disease.
CONCLUSIONS: Despite variability across studies, the evidence suggests that RAS/KRAS-mutated mCRC is associated with poorer survival outcomes compared with wild-type disease in the 1L setting. These findings highlight an unmet need in RAS/KRAS-mutated mCRC and underscore the importance of continued development of biomarker-driven and targeted therapeutic strategies for this population.
METHODS: A systematic search of Embase, Cochrane Library, and google scholar was conducted through October 15, 2025, supplemented by manual searches of conference proceedings from the two years preceding the search date. Eligible publications included randomized controlled trials (RCTs) and non-randomized studies evaluating first-line treatment outcomes in patients with RAS/KRAS-mutated mCRC. Of 2,629 records identified, 79 publications (48 RCTs and 31 non-RCTs) were included in the SLR. Of these, five publications evaluating the independent prognostic impact of RAS/KRAS mutations relative to wild-type disease were prioritized for this analysis. PFS and OS outcomes were extracted and summarized descriptively.
RESULTS: Across included studies, findings were mixed; however, a directional trend toward poorer survival outcomes among RAS/KRAS-mutated patients was observed. In studies reporting statistically significant differences, RAS/KRAS mutations were associated with a 36%-47% higher risk of progression and a 24%-60% higher risk of mortality versus wild-type disease. Although the magnitude of the association varied across studies, no study demonstrated a statistically significant survival advantage for RAS/KRAS-mutated disease.
CONCLUSIONS: Despite variability across studies, the evidence suggests that RAS/KRAS-mutated mCRC is associated with poorer survival outcomes compared with wild-type disease in the 1L setting. These findings highlight an unmet need in RAS/KRAS-mutated mCRC and underscore the importance of continued development of biomarker-driven and targeted therapeutic strategies for this population.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
CO115
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Oncology