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