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

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Abstract

Background

Effective targeting of RAS mutations has proven elusive until recently. Novel agents directly targeting KRAS G12C have shown promise in early-phase clinical trials that included patients with metastatic colorectal cancer. Prior reports have suggested that G12C mutation may be predictive of poor outcome.

Objective

Assessment of the specific characteristics and prognostic implications of individual RAS mutation subtypes in patients with metastatic colorectal cancer.

Patients and methods

Retrospective review of individual RAS mutation types from the South Australian Metastatic Colorectal Registry between 2006 and 2020.

Results

Of the 5165 patients entered onto the registry, 2305 (45%) had RAS mutation results available. 772 (33%) had a RAS mutation. The nature of the RAS mutation was available in 668 (87% of those with RAS mutation). Rare mutations (outside codons 12 and 13) made up 12.6% of the total. There were numerical differences in survival between the specific RAS mutation subgroups, with the longest median overall survival (30 months) observed in those with G12S mutations. However, there was no statistical difference in survival when comparing the various RAS mutations, including the comparison of G12C to G12S (p = 0.38). Patients with cancer harbouring rare RAS mutations had a median survival of 30 months.

Conclusions

Whilst the G12S mutation was associated with the longest survival numerically, the observed survival for patients with the most common RAS mutations (G12C, G12V, G12A, G12D and G13D) did not significantly differ.

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Authors and Affiliations

  1. Department of Medical Oncology, The Queen Elizabeth Hospital and University of Adelaide, Adelaide, SA, Australia

    Anas Alawawdeh, Amanda Rose Townsend, Annabelle Smith & Timothy Jay Price

  2. Division of Surgery, Flinders Medical Centre, Adelaide, SA, Australia

    Cynthia Piantadosi & Rob Padbury

  3. Department of Medical Oncology, Flinders Medical Centre and Flinders University, Adelaide, SA, Australia

    Christos Stelios Karapetis & Amitesh Chandra Roy

  4. Department of Surgery, Royal Adelaide Hospital, Adelaide, SA, Australia

    James Moore

  5. Department of Surgery, The Queen Elizabeth Hospital, Adelaide, SA, Australia

    Guy Maddern

  6. Discipline of Surgery, University of Adelaide, Adelaide, SA, Australia

    Guy Maddern

  7. Sansom Institute for Health Research, Adelaide, SA, Australia

    David Roder

  8. TQEH, 28 Woodville Road, Woodville, SA, 5011, Australia

    Timothy Jay Price

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  1. Anas Alawawdeh
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Corresponding author

Correspondence to Timothy Jay Price.

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Funding

No external funding was used in the preparation of this article.

Conflict of interest

Anas Alawawdeh, Cynthia Piantadosi, Amanda Rose Townsend, Christos Stelios Karapetis, Rob Padbury, Amitesh Chandra Roy, James Moore, Guy Maddern, David Roder, Annabelle Smith and Timothy Jay Price declare that they have no conflicts of interest that might be relevant to the contents of this article.

Availability of data and material

The data are part of the South Australian Metastatic Colorectal Registry and will be made available on request to the oversight committee.

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All authors have contributed significantly to the article and are in agreement with the contents of the article.

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Alawawdeh, A., Piantadosi, C., Townsend, A.R. et al. Prognostic Differences of RAS Mutations: Results from the South Australian Metastatic Colorectal Registry. Targ Oncol 17, 35–41 (2022). https://doi.org/10.1007/s11523-021-00856-9

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  • DOI: https://doi.org/10.1007/s11523-021-00856-9

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