REAL-WORLD SURVIVAL OUTCOMES IN KRAS(G12C) METASTATIC COLORECTAL CANCER IN THE UNITED STATES AND CANADA: A SYSTEMATIC LITERATURE REVIEW
Author(s)
Shivom Prajapati, M.Pharm1, Sukriti Sharma, M.Sc.1, Sumeet Attri, M.Pharm1, Barinder Singh, RPh2;
1Pharmacoevidence, Mohali, India, 2Pharmacoevidence, London, United Kingdom
1Pharmacoevidence, Mohali, India, 2Pharmacoevidence, London, United Kingdom
OBJECTIVES: Global prevalence of the KRAS(G12C) mutation is approximately 3.0% in metastatic colorectal cancer (mCRC), defining a small but clinically important subgroup. Despite advances in targeted therapy, chemotherapy remains widely used. This systematic literature review evaluated real-world survival outcomes associated with systemic therapies in adults with KRAS(G12C)-mutant mCRC.
METHODS: EMBASE® and MEDLINE® were systematically searched through January 2026 for English-language real-world studies conducted in the US and Canada. A standard two-review and quality control process, aligned with Cochrane and Health Technology Assessment guidelines, was employed to ensure robust evidence generation.
RESULTS: Of 297 screened publications, seven studies met eligibility criteria. All were retrospective cohort studies, with six studies conducted in the US and one in Canada. Among 20,161 mCRC patients, 4.9% harboured the KRAS(G12C) mutation. Oxaliplatin-based chemotherapy was the most commonly utilized first-line therapy (60.3% and 85.7%, n=2), while irinotecan-based regimens were primarily used in the second-line setting (56.5% and 87.2%, n=2). Third-line treatments included FOLFOXIRI, regorafenib, and trifluridine/tipiracil. Median OS (mOS) among chemotherapy-treated KRAS(G12C)-mutant patients ranged from 5.2 to 62.4 months (n=7, any line). In the first-line, mOS ranged from 16.1 to 33.5 months (n=4), while in the second-line, mOS was 9.7 months and 33.5 months (n=2). OS was significantly worse for KRAS(G12C) compared with other KRAS mutations (p<0.001) and RAS/BRAF wild type (HR 1.78; p=0.01). Median PFS (mPFS) ranged from 2.1 to 20.9 months (n=5, any line). In the first-line setting, mPFS ranged from 4.8 to 20.9 months (n=5), while in the second-line, mPFS ranged from 3.9 to 4.8 months (n=3).
CONCLUSIONS: Real-world survival outcomes remain poor for chemotherapy-treated KRAS(G12C)-mutant mCRC compared with RAS/BRAF wild-type or other KRAS mutations, highlighting a significant unmet need. The recent FDA approval of sotorasib in January 2025 may potentially mitigate the unmet need of targeted therapy in KRAS(G12C)-mutant mCRC patients, particularly those who failed chemotherapy.
METHODS: EMBASE® and MEDLINE® were systematically searched through January 2026 for English-language real-world studies conducted in the US and Canada. A standard two-review and quality control process, aligned with Cochrane and Health Technology Assessment guidelines, was employed to ensure robust evidence generation.
RESULTS: Of 297 screened publications, seven studies met eligibility criteria. All were retrospective cohort studies, with six studies conducted in the US and one in Canada. Among 20,161 mCRC patients, 4.9% harboured the KRAS(G12C) mutation. Oxaliplatin-based chemotherapy was the most commonly utilized first-line therapy (60.3% and 85.7%, n=2), while irinotecan-based regimens were primarily used in the second-line setting (56.5% and 87.2%, n=2). Third-line treatments included FOLFOXIRI, regorafenib, and trifluridine/tipiracil. Median OS (mOS) among chemotherapy-treated KRAS(G12C)-mutant patients ranged from 5.2 to 62.4 months (n=7, any line). In the first-line, mOS ranged from 16.1 to 33.5 months (n=4), while in the second-line, mOS was 9.7 months and 33.5 months (n=2). OS was significantly worse for KRAS(G12C) compared with other KRAS mutations (p<0.001) and RAS/BRAF wild type (HR 1.78; p=0.01). Median PFS (mPFS) ranged from 2.1 to 20.9 months (n=5, any line). In the first-line setting, mPFS ranged from 4.8 to 20.9 months (n=5), while in the second-line, mPFS ranged from 3.9 to 4.8 months (n=3).
CONCLUSIONS: Real-world survival outcomes remain poor for chemotherapy-treated KRAS(G12C)-mutant mCRC compared with RAS/BRAF wild-type or other KRAS mutations, highlighting a significant unmet need. The recent FDA approval of sotorasib in January 2025 may potentially mitigate the unmet need of targeted therapy in KRAS(G12C)-mutant mCRC patients, particularly those who failed chemotherapy.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
RWD159
Topic
Real World Data & Information Systems
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Oncology, STA: Multiple/Other Specialized Treatments