The efficacy of immunotherapy in non-small cell lung cancer with KRAS mutation: a systematic review and meta-analysis
Abstract Purpose The KRAS mutation is highly prevalent in NSCLC and is associated with poor efficacy of immunotherapy. Nevertheless, the impact of KRAS mutation, mutation subtypes, and co-mutations on the effectiveness of immunotherapy remains uncertain. This study aimed to assess the influence of t...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-11-01
|
| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-024-03498-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850179708689317888 |
|---|---|
| author | Rui Zhao Yang Shu Wei Xu Fengxian Jiang Pancen Ran Liying Pan Jingliang Wang Weihao Wang Jing Zhao Yahui Wang Guobin Fu |
| author_facet | Rui Zhao Yang Shu Wei Xu Fengxian Jiang Pancen Ran Liying Pan Jingliang Wang Weihao Wang Jing Zhao Yahui Wang Guobin Fu |
| author_sort | Rui Zhao |
| collection | DOAJ |
| description | Abstract Purpose The KRAS mutation is highly prevalent in NSCLC and is associated with poor efficacy of immunotherapy. Nevertheless, the impact of KRAS mutation, mutation subtypes, and co-mutations on the effectiveness of immunotherapy remains uncertain. This study aimed to assess the influence of the KRAS mutation on the effectiveness of immunotherapy in NSCLC, specifically examining different subtypes of KRAS mutations and co-mutations. Methods We performed an extensive search of multiple databases, covering the period from January 1, 2000, to December 5, 2023. A total of 24 articles met our inclusion criteria and were included in this study. A comparative analysis assessed the influence of different subgroups, including KRAS mutation, KRAS wild-type, KRAS G12C mutation, KRAS G12D mutation, and KRAS with co-mutations in NSCLC with immunotherapy. The study outcomes include HR, with corresponding 95% CI and P-values for OS and PFS using Review Manager 5.4 software for the meta-analysis. Result The KRAS mutation appears to have a more beneficial impact on OS (HR 0.54 [95% CI: 0.41–0.71]; P < 0.00001) and PFS (HR 0.63 [95% CI: 0.53–0.76]; P < 0.00001) in NSCLC patients receiving immunotherapy compared to those without immunotherapy. The presence of KRASG12C mutation has been found to have a positive impact on PFS (HR 0.39 [95% CI: 0.25–0.62]; P < 0.0001) in NSCLC patients who undergo immunotherapy, compared to those who did not receive immunotherapy. KRAS non-G12D mutation is considerably associated with longer OS (HR 1.52 [95% CI: 1.10–2.10]; P = 0.01). The clinical benefit in OS between patients without STK11 co-mutation and those who have KRAS mutation with STK11 is significant (HR 1.46 [95% CI: 1.10–1.93]; P = 0.008). Comparing the impact of OS patients without KEAP1/NFE2L2 mutation to those with KRAS and KEAP1/NFE2L2 co-mutations showed a significant impact (HR 1.89 [95% CI: 1.33–2.68]; P = 0.0004). Conclusion The KRAS mutation and KRAS G12C mutation confer benefits that impact OS and PFS in NSCLC patients treated with immunotherapy. However, the KRAS G12D mutation negatively impacts OS compared to the KRAS non-G12D mutation. Furthermore, KRAS co-mutations involving STK11 and KEAP1/NFE2L2 are associated with a negative impact on the efficacy of immunotherapy in NSCLC patients. |
| format | Article |
| id | doaj-art-856f91f3fa3240f6addacce2db4a42fd |
| institution | OA Journals |
| issn | 1475-2867 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-856f91f3fa3240f6addacce2db4a42fd2025-08-20T02:18:25ZengBMCCancer Cell International1475-28672024-11-0124111710.1186/s12935-024-03498-9The efficacy of immunotherapy in non-small cell lung cancer with KRAS mutation: a systematic review and meta-analysisRui Zhao0Yang Shu1Wei Xu2Fengxian Jiang3Pancen Ran4Liying Pan5Jingliang Wang6Weihao Wang7Jing Zhao8Yahui Wang9Guobin Fu10Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityShandong UniversityShandong University of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineThe Clinical Medical College, Shandong First Medical University, (Shandong Academy of Medical Sciences)The Clinical Medical College, Shandong First Medical University, (Shandong Academy of Medical Sciences)Shandong University of Traditional Chinese MedicineDepartment of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityAbstract Purpose The KRAS mutation is highly prevalent in NSCLC and is associated with poor efficacy of immunotherapy. Nevertheless, the impact of KRAS mutation, mutation subtypes, and co-mutations on the effectiveness of immunotherapy remains uncertain. This study aimed to assess the influence of the KRAS mutation on the effectiveness of immunotherapy in NSCLC, specifically examining different subtypes of KRAS mutations and co-mutations. Methods We performed an extensive search of multiple databases, covering the period from January 1, 2000, to December 5, 2023. A total of 24 articles met our inclusion criteria and were included in this study. A comparative analysis assessed the influence of different subgroups, including KRAS mutation, KRAS wild-type, KRAS G12C mutation, KRAS G12D mutation, and KRAS with co-mutations in NSCLC with immunotherapy. The study outcomes include HR, with corresponding 95% CI and P-values for OS and PFS using Review Manager 5.4 software for the meta-analysis. Result The KRAS mutation appears to have a more beneficial impact on OS (HR 0.54 [95% CI: 0.41–0.71]; P < 0.00001) and PFS (HR 0.63 [95% CI: 0.53–0.76]; P < 0.00001) in NSCLC patients receiving immunotherapy compared to those without immunotherapy. The presence of KRASG12C mutation has been found to have a positive impact on PFS (HR 0.39 [95% CI: 0.25–0.62]; P < 0.0001) in NSCLC patients who undergo immunotherapy, compared to those who did not receive immunotherapy. KRAS non-G12D mutation is considerably associated with longer OS (HR 1.52 [95% CI: 1.10–2.10]; P = 0.01). The clinical benefit in OS between patients without STK11 co-mutation and those who have KRAS mutation with STK11 is significant (HR 1.46 [95% CI: 1.10–1.93]; P = 0.008). Comparing the impact of OS patients without KEAP1/NFE2L2 mutation to those with KRAS and KEAP1/NFE2L2 co-mutations showed a significant impact (HR 1.89 [95% CI: 1.33–2.68]; P = 0.0004). Conclusion The KRAS mutation and KRAS G12C mutation confer benefits that impact OS and PFS in NSCLC patients treated with immunotherapy. However, the KRAS G12D mutation negatively impacts OS compared to the KRAS non-G12D mutation. Furthermore, KRAS co-mutations involving STK11 and KEAP1/NFE2L2 are associated with a negative impact on the efficacy of immunotherapy in NSCLC patients.https://doi.org/10.1186/s12935-024-03498-9KRAS mutationKRAS mutation subtypeKRAS co-mutationImmunotherapyNSCLCMeta-analysis |
| spellingShingle | Rui Zhao Yang Shu Wei Xu Fengxian Jiang Pancen Ran Liying Pan Jingliang Wang Weihao Wang Jing Zhao Yahui Wang Guobin Fu The efficacy of immunotherapy in non-small cell lung cancer with KRAS mutation: a systematic review and meta-analysis Cancer Cell International KRAS mutation KRAS mutation subtype KRAS co-mutation Immunotherapy NSCLC Meta-analysis |
| title | The efficacy of immunotherapy in non-small cell lung cancer with KRAS mutation: a systematic review and meta-analysis |
| title_full | The efficacy of immunotherapy in non-small cell lung cancer with KRAS mutation: a systematic review and meta-analysis |
| title_fullStr | The efficacy of immunotherapy in non-small cell lung cancer with KRAS mutation: a systematic review and meta-analysis |
| title_full_unstemmed | The efficacy of immunotherapy in non-small cell lung cancer with KRAS mutation: a systematic review and meta-analysis |
| title_short | The efficacy of immunotherapy in non-small cell lung cancer with KRAS mutation: a systematic review and meta-analysis |
| title_sort | efficacy of immunotherapy in non small cell lung cancer with kras mutation a systematic review and meta analysis |
| topic | KRAS mutation KRAS mutation subtype KRAS co-mutation Immunotherapy NSCLC Meta-analysis |
| url | https://doi.org/10.1186/s12935-024-03498-9 |
| work_keys_str_mv | AT ruizhao theefficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT yangshu theefficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT weixu theefficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT fengxianjiang theefficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT pancenran theefficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT liyingpan theefficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT jingliangwang theefficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT weihaowang theefficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT jingzhao theefficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT yahuiwang theefficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT guobinfu theefficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT ruizhao efficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT yangshu efficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT weixu efficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT fengxianjiang efficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT pancenran efficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT liyingpan efficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT jingliangwang efficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT weihaowang efficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT jingzhao efficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT yahuiwang efficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis AT guobinfu efficacyofimmunotherapyinnonsmallcelllungcancerwithkrasmutationasystematicreviewandmetaanalysis |