Real-World Effectiveness of Systemic Therapies in Adults with KRAS(G12C) Metastatic Colorectal Cancer in Europe: A Systematic Literature Review
Author(s)
Sumeet Attri, M.Pharm1, Sukriti Sharma, M.Sc.1, Shivom Prajapati, M.Pharm1, Ritesh Dubey, PharmD1, Barinder Singh, RPh2.
1Pharmacoevidence, Mohali, India, 2Pharmacoevidence, London, United Kingdom.
1Pharmacoevidence, Mohali, India, 2Pharmacoevidence, London, United Kingdom.
OBJECTIVES: Global prevalence of KRAS(G12C) mutation is 3.0% in metastatic colorectal cancer (mCRC), defining a small but clinically important subgroup. While targeted therapies are emerging, chemotherapy remains widely used. A systematic literature review (SLR) was conducted to assess the impact of systemic therapies on survival outcomes in adults with KRAS(G12C)-mutant mCRC in real-world studies across Europe.
METHODS: EMBASE® and MEDLINE® were systematically searched up to June 2025 for English-language real-world studies conducted in Europe. A standard two-review and quality control process, aligned with Cochrane and HTA guidelines, was employed to ensure robust evidence generation.
RESULTS: Of 262 publications screened, 10 studies (12 publications) met eligibility criteria. Most were retrospective cohort studies (n=8), predominantly conducted in Italy (n=7). Across 18,078 mCRC patients from 10 studies, 3.4% (n=620) had KRAS(G12C)-mutation. Overall survival (OS) and progression-free survival (PFS) was reported in nine and seven studies, respectively. Among chemotherapy-treated KRAS(G12C)-mutant mCRC patients, median OS (mOS) ranged from 10.6 to 52.9 months (n=7, any line). In first-line (1L) setting, mOS ranged from 18.0 to 37.3 months (n=3), while in second-line (2L), mOS was reported as 10.6 months (n=1). Median PFS (mPFS) ranged from 3.0 to 13.0 months (n=6, any line), with mPFS in 1L ranging from 7.0 to 13.0 months (n=3), while 4.0 months and 4.8 months in 2L (n=1 each). Further, in 1L setting, irinotecan-based chemotherapy was associated with statistically significantly higher PFS (Hazard Ratio: 0.52, p=0.04; 0.62, p=0.02; mPFS: 9.0 vs. 7.0 months) and OS (mOS: 28.9 vs. 21.1 months; 22.0 vs. 18.0 months) compared to oxaliplatin-based chemotherapy.
CONCLUSIONS: This SLR highlights that real-world survival remains poor for KRAS(G12C)-mutant mCRC patients treated with chemotherapy. While irinotecan-based regimens show better survival in 1L setting than oxaliplatin-based chemotherapy, their role in later lines remains unclear. These results underscore the need for more effective targeted therapies in this high-risk population.
METHODS: EMBASE® and MEDLINE® were systematically searched up to June 2025 for English-language real-world studies conducted in Europe. A standard two-review and quality control process, aligned with Cochrane and HTA guidelines, was employed to ensure robust evidence generation.
RESULTS: Of 262 publications screened, 10 studies (12 publications) met eligibility criteria. Most were retrospective cohort studies (n=8), predominantly conducted in Italy (n=7). Across 18,078 mCRC patients from 10 studies, 3.4% (n=620) had KRAS(G12C)-mutation. Overall survival (OS) and progression-free survival (PFS) was reported in nine and seven studies, respectively. Among chemotherapy-treated KRAS(G12C)-mutant mCRC patients, median OS (mOS) ranged from 10.6 to 52.9 months (n=7, any line). In first-line (1L) setting, mOS ranged from 18.0 to 37.3 months (n=3), while in second-line (2L), mOS was reported as 10.6 months (n=1). Median PFS (mPFS) ranged from 3.0 to 13.0 months (n=6, any line), with mPFS in 1L ranging from 7.0 to 13.0 months (n=3), while 4.0 months and 4.8 months in 2L (n=1 each). Further, in 1L setting, irinotecan-based chemotherapy was associated with statistically significantly higher PFS (Hazard Ratio: 0.52, p=0.04; 0.62, p=0.02; mPFS: 9.0 vs. 7.0 months) and OS (mOS: 28.9 vs. 21.1 months; 22.0 vs. 18.0 months) compared to oxaliplatin-based chemotherapy.
CONCLUSIONS: This SLR highlights that real-world survival remains poor for KRAS(G12C)-mutant mCRC patients treated with chemotherapy. While irinotecan-based regimens show better survival in 1L setting than oxaliplatin-based chemotherapy, their role in later lines remains unclear. These results underscore the need for more effective targeted therapies in this high-risk population.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO203
Topic
Clinical Outcomes, Real World Data & Information Systems, Study Approaches
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Oncology, Rare & Orphan Diseases