Prognostic Differences of RAS Mutations: Results from the South Australian Metastatic Colorectal Registry

Alawawdeh, Anas; Piantadosi, Cynthia; Townsend, Amanda; Karapetis, Christos S.; Padbury, Rob; Roy, Amitesh; Moore, James; Maddern, Guy; Roder, David; Smith, Alistair; Price, Timothy

doi:10.1007/s11523-021-00856-9

Cited by 3 publications

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“…Outcome analysis from a population-based registry of Australian patients with mCRC and a real-life and population-based cohort of Nordic patients with mCRC or locally advanced untreatable CRC did not reveal any difference between patients with KRAS G12C and those with other KRASm . 76 , 77 In contrast, 4 recent studies from Japan, US, and China reported poorer survival rates and significantly inferior PFS in patients with KRAS G12C than in those with other KRASm . 69 , 78-80 These conflicting findings have been attributed to the difference in average patient age, disease stage, and data sources (selected patient populations vs population-based/real-life registries).…”

Section: Discussionmentioning

confidence: 96%

“… 69 , 78-80 These conflicting findings have been attributed to the difference in average patient age, disease stage, and data sources (selected patient populations vs population-based/real-life registries). 76 Given these findings, a deeper investigation into the biological and mechanistic role of KRAS G12C (vis-à-vis other KRASm ) may possibly provide better insights into the clinical significance of this mutation.…”

Section: Discussionmentioning

confidence: 99%

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Prevalence ofKRASG12C Mutation and Co-mutations and Associated Clinical Outcomes in Patients With Colorectal Cancer: A Systematic Literature Review

et al. 2023

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Purpose A systematic literature review was conducted to estimate the global prevalence of Kirsten rat sarcoma virus gene (KRAS) mutations, with an emphasis on the clinically significant KRAS G12C mutation, and to estimate the prognostic significance of these mutations in patients with colorectal cancer (CRC). Design Relevant English-language publications in the Embase, MEDLINE, and the Cochrane Library databases (from 2009 to 2021) and congress presentations (from 2016 to 2021) were reviewed. Eligible studies were those that reported the prevalence and clinical outcomes of the KRAS G12C mutation in patients with CRC. Results A total of 137 studies (interventional [n = 8], post hoc analyses of randomized clinical trials [n = 6], observational [n = 122], and longitudinal [n =1]) were reviewed. Sixty-eight studies reported the prevalence of KRAS mutations (KRASm) in 42 810 patients with CRC. The median global prevalence of KRASm was 38% (range, 13.3%-58.9%) and that of the KRAS G12C mutation (KRAS G12C) 3.1% (range, 0.7%-14%). Available evidence suggests that KRASm are possibly more common in tumors that develop on the right side of the colon. Limited evidence suggests a lower objective response rate and inferior disease-free/relapse-free survival in patients with KRAS G12C compared with patients with KRASwt or other KRASm. Conclusion Our analysis reveals that KRAS G12C is prevalent in 3% of patients with CRC. Available evidence suggests a poor prognosis for patients with KRAS G12C. Right-sided tumors were more likely to harbor KRASm; however, their role in determining clinical outcomes needs to be investigated further.

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