Canadian Consensus Recommendations on the Management of KRAS G12C-Mutated NSCLC
Activating mutations in <i>Kirsten rat sarcoma viral oncogene homologue (KRAS)</i>, in particular, a point mutation leading to a glycine-to-cysteine substitution at codon 12 (G12C), are among the most frequent genomic alterations in non-small cell lung cancer (NSCLC). Several agents targ...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/30/7/476 |
| _version_ | 1797589677703692288 |
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| author | Parneet K. Cheema Shantanu O. Banerji Normand Blais Quincy S.-C. Chu Rosalyn A. Juergens Natasha B. Leighl Adrian Sacher Brandon S. Sheffield Stephanie Snow Mark Vincent Paul F. Wheatley-Price Stephen Yip Barbara L. Melosky |
| author_facet | Parneet K. Cheema Shantanu O. Banerji Normand Blais Quincy S.-C. Chu Rosalyn A. Juergens Natasha B. Leighl Adrian Sacher Brandon S. Sheffield Stephanie Snow Mark Vincent Paul F. Wheatley-Price Stephen Yip Barbara L. Melosky |
| author_sort | Parneet K. Cheema |
| collection | DOAJ |
| description | Activating mutations in <i>Kirsten rat sarcoma viral oncogene homologue (KRAS)</i>, in particular, a point mutation leading to a glycine-to-cysteine substitution at codon 12 (G12C), are among the most frequent genomic alterations in non-small cell lung cancer (NSCLC). Several agents targeting KRAS G12C have recently entered clinical development. Sotorasib, a first-in-class specific small molecule that irreversibly inhibits KRAS G12C, has since obtained Health Canada approval. The emergence of novel KRAS-targeted therapies warrants the development of evidence-based consensus recommendations to help clinicians better understand and contextualize the available data. A Canadian expert panel was convened to define the key clinical questions, review recent evidence, and discuss and agree on recommendations for the treatment of advanced <i>KRAS G12C</i>-mutated NSCLC. The panel agreed that testing for KRAS G12C should be performed as part of a comprehensive panel that includes current standard-of-care biomarkers. Sotorasib, the only approved KRAS G12C inhibitor in Canada, is recommended for patients with advanced KRAS G12C-mutated NSCLC who progressed on guideline-recommended first-line standard of care for advanced NSCLC without driver alterations (immune-checkpoint inhibitor(s) [ICIs] +/− chemotherapy). Sotorasib could also be offered as second-line therapy to patients who progressed on ICI monotherapy that are not candidates for a platinum doublet and those that received first-line chemotherapy with a contraindication to ICIs. Preliminary data indicate the activity of KRAS G12C inhibitors in brain metastases; however, the evidence is insufficient to make specific recommendations. Regular liver function monitoring is recommended when patients are prescribed KRAS G12C inhibitors due to risk of hepatotoxicity. |
| first_indexed | 2024-03-11T01:09:57Z |
| format | Article |
| id | doaj.art-ab0cb512b2d24cbeafaef622627ed0b6 |
| institution | Directory Open Access Journal |
| issn | 1198-0052 1718-7729 |
| language | English |
| last_indexed | 2024-03-11T01:09:57Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Oncology |
| spelling | doaj.art-ab0cb512b2d24cbeafaef622627ed0b62023-11-18T18:55:46ZengMDPI AGCurrent Oncology1198-00521718-77292023-07-013076473649610.3390/curroncol30070476Canadian Consensus Recommendations on the Management of KRAS G12C-Mutated NSCLCParneet K. Cheema0Shantanu O. Banerji1Normand Blais2Quincy S.-C. Chu3Rosalyn A. Juergens4Natasha B. Leighl5Adrian Sacher6Brandon S. Sheffield7Stephanie Snow8Mark Vincent9Paul F. Wheatley-Price10Stephen Yip11Barbara L. Melosky12Division of Medical Oncology, William Osler Health System, University of Toronto, Brampton, ON L6R 3J7, CanadaCancerCare Manitoba Research Institute, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0V9, CanadaDepartment of Medicine, Centre Hospitalier de l’Université de Montréal, University of Montreal, Montreal, QC H2X 3E4, CanadaDivision of Medical Oncology, Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 1Z2, CanadaDepartment of Medical Oncology, Juravinski Cancer Centre, McMaster University, Hamilton, ON L8V 5C2, CanadaDepartment of Medicine, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5S 1A8, CanadaDepartment of Medicine, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5S 1A8, CanadaDepartment of Laboratory Medicine, William Osler Health System, Brampton, ON L6R 3J7, CanadaDivision of Medical Oncology, Department of Medicine, QEII Health Sciences Centre, Dalhousie University, Halifax, NS B3H 2Y9, CanadaDepartment of Medical Oncology, London Regional Cancer Program, London, ON N6A 5W9, CanadaDepartment of Medicine, The Ottawa Hospital Research Institute, The Ottawa Hospital, University of Ottawa, Ottawa, ON K1H 8L6, CanadaBC Cancer, Vancouver, University of British Columbia, Vancouver, BC V6T 1Z4, CanadaDepartment of Medical Oncology, BC Cancer-Vancouver Centre, Vancouver, BC V5Z 4E6, CanadaActivating mutations in <i>Kirsten rat sarcoma viral oncogene homologue (KRAS)</i>, in particular, a point mutation leading to a glycine-to-cysteine substitution at codon 12 (G12C), are among the most frequent genomic alterations in non-small cell lung cancer (NSCLC). Several agents targeting KRAS G12C have recently entered clinical development. Sotorasib, a first-in-class specific small molecule that irreversibly inhibits KRAS G12C, has since obtained Health Canada approval. The emergence of novel KRAS-targeted therapies warrants the development of evidence-based consensus recommendations to help clinicians better understand and contextualize the available data. A Canadian expert panel was convened to define the key clinical questions, review recent evidence, and discuss and agree on recommendations for the treatment of advanced <i>KRAS G12C</i>-mutated NSCLC. The panel agreed that testing for KRAS G12C should be performed as part of a comprehensive panel that includes current standard-of-care biomarkers. Sotorasib, the only approved KRAS G12C inhibitor in Canada, is recommended for patients with advanced KRAS G12C-mutated NSCLC who progressed on guideline-recommended first-line standard of care for advanced NSCLC without driver alterations (immune-checkpoint inhibitor(s) [ICIs] +/− chemotherapy). Sotorasib could also be offered as second-line therapy to patients who progressed on ICI monotherapy that are not candidates for a platinum doublet and those that received first-line chemotherapy with a contraindication to ICIs. Preliminary data indicate the activity of KRAS G12C inhibitors in brain metastases; however, the evidence is insufficient to make specific recommendations. Regular liver function monitoring is recommended when patients are prescribed KRAS G12C inhibitors due to risk of hepatotoxicity.https://www.mdpi.com/1718-7729/30/7/476KRAS G12CNSCLCtargeted therapyimmune checkpoint inhibitorsmutation testingresistance |
| spellingShingle | Parneet K. Cheema Shantanu O. Banerji Normand Blais Quincy S.-C. Chu Rosalyn A. Juergens Natasha B. Leighl Adrian Sacher Brandon S. Sheffield Stephanie Snow Mark Vincent Paul F. Wheatley-Price Stephen Yip Barbara L. Melosky Canadian Consensus Recommendations on the Management of KRAS G12C-Mutated NSCLC Current Oncology KRAS G12C NSCLC targeted therapy immune checkpoint inhibitors mutation testing resistance |
| title | Canadian Consensus Recommendations on the Management of KRAS G12C-Mutated NSCLC |
| title_full | Canadian Consensus Recommendations on the Management of KRAS G12C-Mutated NSCLC |
| title_fullStr | Canadian Consensus Recommendations on the Management of KRAS G12C-Mutated NSCLC |
| title_full_unstemmed | Canadian Consensus Recommendations on the Management of KRAS G12C-Mutated NSCLC |
| title_short | Canadian Consensus Recommendations on the Management of KRAS G12C-Mutated NSCLC |
| title_sort | canadian consensus recommendations on the management of kras g12c mutated nsclc |
| topic | KRAS G12C NSCLC targeted therapy immune checkpoint inhibitors mutation testing resistance |
| url | https://www.mdpi.com/1718-7729/30/7/476 |
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