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KRAS as a Prognostic and Predictive Marker in Metastatic Non-Small Cell Lung Carcinoma: A Systematic Review
Sheereen Fatima1, Nirav Pansuriya2, Alisha Lakhani3,4
1Cancer Center, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, IND.
Abstract:
Metastatic non-small cell lung cancer (NSCLC) poses a significant clinical challenge, prompting a focused investigation into the role of KRAS mutations in prognosis and treatment response. Targeted therapies offer promising avenues for intervention, motivating a comprehensive analysis of existing evidence. Conducted in June 2023, our review delved into MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase, Scopus, and the Cochrane Register of Controlled Trials. Rigorous inclusion and exclusion criteria guided the selection of 12 articles, comprising two randomized controlled trials (RCTs) and 10 observational studies. Multiple investigators independently executed data extraction, evaluating prognostic factors (overall and progression-free survival) and predictive outcomes (treatment and objective response). The Newcastle-Ottawa Scale (NOS) and modified Jadad scores were used for study quality assessment of observational studies and RCTs, respectively. From an initial pool of 120 articles, the 12 selected studies, spanning 2013 to 2022, encompassed 2,845 metastatic NSCLC patients. KRAS mutations, particularly the G12C variant, emerged as a pivotal factor influencing treatment response. Notably, KRAS wild type patients displayed enhanced responses to platinum-based chemotherapy, while those with KRAS mutations exhibited favourable outcomes with immune checkpoint inhibitors (ICIs). The role of KRAS mutations as prognostic indicators in metastatic NSCLC is underscored by this systematic review, with implications for both survival and treatment response. The discernment between KRAS wild type and mutant patients offers insights into tailored therapeutic strategies, with platinum-based chemotherapy and immune checkpoint inhibitors emerging as context-dependent options. Nevertheless, more research is required to solidify the predictive role of KRAS and explore the efficacy of KRAS inhibitors and other targeted therapies, paving the way for refined and personalized interventions in the management of metastatic NSCLC.
Insights
KRAS mutations impact metastatic non-small cell lung cancer (NSCLC) outcomes. Wild-type KRAS patients respond better to chemotherapy, while mutant KRAS patients benefit from immune checkpoint inhibitors, guiding personalized NSCLC treatment.
Area of Science:
- Oncology
- Genetics
- Clinical Trials
Background:
- Metastatic non-small cell lung cancer (NSCLC) presents significant challenges.
- KRAS mutations are increasingly recognized as critical in NSCLC.
- Targeted therapies necessitate understanding KRAS mutation roles.
Purpose of the Study:
- To systematically review the prognostic and predictive roles of KRAS mutations in metastatic NSCLC.
- To analyze treatment response based on KRAS mutation status.
- To inform personalized therapeutic strategies for NSCLC patients.
Main Methods:
- Systematic review of MEDLINE, Embase, Scopus, and Cochrane Register (June 2023).
- Inclusion of 12 studies (2 RCTs, 10 observational) from 2013-2022, involving 2,845 patients.
- Data extraction on survival and treatment response; quality assessment using NOS and modified Jadad scores.
Main Results:
- KRAS mutations, especially G12C, significantly influence treatment response in metastatic NSCLC.
- KRAS wild-type patients showed better response to platinum-based chemotherapy.
- KRAS-mutated patients demonstrated favorable outcomes with immune checkpoint inhibitors (ICIs).
Conclusions:
- KRAS mutations are important prognostic indicators in metastatic NSCLC.
- Distinguishing KRAS wild-type and mutant status guides selection of chemotherapy or ICIs.
- Further research on KRAS inhibitors and targeted therapies is needed for personalized NSCLC management.
