EFFICACY AND SAFETY OF FIRST-LINE TREATMENT STRATEGIES IN RAS/KRAS-MUTATED 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: Rat sarcoma (RAS) mutations, including kirsten rat sarcoma (KRAS) alterations, are common in metastatic colorectal cancer (mCRC) and are associated with limited therapeutic options and poor outcomes. We conducted a systematic literature review to evaluate clinical outcomes associated with first-line (1L) treatment strategies in RAS/KRAS-mutated mCRC.
METHODS: Embase, Cochrane Library, and google scholar were searched through October 15, 2025, supplemented by manual searches of congress proceedings from the previous two years. Randomized controlled trials, non-randomized interventional studies and single-arm trials evaluating 1L treatment strategies in RAS/KRAS-mutated mCRC were included.
RESULTS: Of 2,629 records identified, 79 publications met inclusion criteria. In studies evaluating FOLFOX- or CAPOX-based regimens with bevacizumab, median progression-free survival (PFS) ranged from approximately 7.8-12.0 months and median overall survival (OS) ranged from 16.8-32.0 months. FOLFIRI-based bevacizumab regimens demonstrated median PFS of 8.7-14.0 months and median OS of 18.7-30.0 months. FOLFOXIRI-based triplet regimens plus bevacizumab demonstrated objective response rates (ORRs; 66-76%), with PFS ranging from 11.5-12.5 months and OS ranging from 27.0-30.2 months. Anti-epidermal growth factor receptor (EGFR)-based therapies in RAS/KRAS-mutated populations demonstrated median PFS of 5.5-8.9 months and median OS of 13.5-21.1 months across studies. Emerging KRAS G12C-targeted combinations (sotorasib, panitumumab, and FOLFIRI) reported an ORR of 75% and disease control rate (DCR) of 95%, while immunotherapy-based combinations demonstrated ORRs ranging from 69-84% and DCRs exceeding 90% in microsatellite stable disease.
CONCLUSIONS: Existing chemotherapy strategies provide modest control in RAS/KRAS-mutated mCRC, highlighting the persistent unmet need in this difficult-to-treat population. FOLFOXIRI-based regimens appeared to demonstrate more favorable efficacy outcomes across studies, whereas anti-EGFR-based approaches remained suboptimal. Emerging KRAS G12C-targeted and immunotherapy-based combinations demonstrated encouraging early efficacy and may help address the unmet need by meaningfully expanding the treatment landscape.
METHODS: Embase, Cochrane Library, and google scholar were searched through October 15, 2025, supplemented by manual searches of congress proceedings from the previous two years. Randomized controlled trials, non-randomized interventional studies and single-arm trials evaluating 1L treatment strategies in RAS/KRAS-mutated mCRC were included.
RESULTS: Of 2,629 records identified, 79 publications met inclusion criteria. In studies evaluating FOLFOX- or CAPOX-based regimens with bevacizumab, median progression-free survival (PFS) ranged from approximately 7.8-12.0 months and median overall survival (OS) ranged from 16.8-32.0 months. FOLFIRI-based bevacizumab regimens demonstrated median PFS of 8.7-14.0 months and median OS of 18.7-30.0 months. FOLFOXIRI-based triplet regimens plus bevacizumab demonstrated objective response rates (ORRs; 66-76%), with PFS ranging from 11.5-12.5 months and OS ranging from 27.0-30.2 months. Anti-epidermal growth factor receptor (EGFR)-based therapies in RAS/KRAS-mutated populations demonstrated median PFS of 5.5-8.9 months and median OS of 13.5-21.1 months across studies. Emerging KRAS G12C-targeted combinations (sotorasib, panitumumab, and FOLFIRI) reported an ORR of 75% and disease control rate (DCR) of 95%, while immunotherapy-based combinations demonstrated ORRs ranging from 69-84% and DCRs exceeding 90% in microsatellite stable disease.
CONCLUSIONS: Existing chemotherapy strategies provide modest control in RAS/KRAS-mutated mCRC, highlighting the persistent unmet need in this difficult-to-treat population. FOLFOXIRI-based regimens appeared to demonstrate more favorable efficacy outcomes across studies, whereas anti-EGFR-based approaches remained suboptimal. Emerging KRAS G12C-targeted and immunotherapy-based combinations demonstrated encouraging early efficacy and may help address the unmet need by meaningfully expanding the treatment landscape.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
CO63
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy, Relating Intermediate to Long-term Outcomes
Disease
Gastrointestinal Disorders, Oncology