Limited role of KRAS mutation in guiding immunotherapy in advanced non-small-cell lung cancer

Abstract

The success of sotorasib (AMG-510) and adagrasib (MRTX-849) has resolved the problem of non-availability of drugs for patients with KRAS_G12C-mutated non-small-cell lung cancer. However, more research is required before these drugs can be introduced as a first-line treatment for those patients, and there are no available drugs for other non-G12C-mutated patients so far; therefore, immunotherapy remains the optimal first-line treatment in this situation. The role of KRAS in affecting the response to immunotherapy in non-small-cell lung cancer has not been fully elucidated. The purpose of this review was to summarize the impact of KRAS mutations, a highly heterogeneous group, on immunotherapy to provide clinicians and researchers with relevant information that can help guide decision-making.

Plain language summary

Sotorasib (AMG-510) and adagrasib (MRTX-849) have changed the problem of non-availability of targeted drugs for patients with KRAS-mutated lung cancer. However, thus far, immunotherapy remains the optimal treatment for lung cancer patients with KRAS mutations who have not received previous treatment. The role of KRAS in affecting the response to immunotherapy in non-small-cell lung cancer has not been fully elucidated. The purpose of this review was to summarize the impact of KRAS mutations, a highly heterogeneous group, on immunotherapy to provide clinicians and researchers with relevant information that can help guide decision-making.

Keywords::

• co-mutation status
• immunotherapy
• KRAS
• mutation subtypes
• non-small-cell lung cancer

Author contributions

HS Li, CM Liu and Y Wang have each made substantial contributions to the conception and design of the study, acquisition of data and analysis and interpretation of data; drafting the article and revising it critically for important intellectual content; and final approval of the version submitted.

Acknowledgments

The authors would like to thank L-L Yang for her help in writing the draft and Editage (www.editage.cn) for English-language editing.

Financial & competing interests disclosure

This work was supported the National Natural Science Foundation of China (grant no. 82072590) and the Beijing Health Promotion Association (grant no. 2021-053-ZZ). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Funded writing assistance was provided by Editage (www.editage.cn) in the form of English-language editing.

Data availability statement

All data included in this study are available upon request by contact with the corresponding author.

Additional information

Funding

This work was supported the National Natural Science Foundation of China (grant no. 82072590) and the Beijing Health Promotion Association (grant no. 2021-053-ZZ). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.