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. 2020 Sep;12(9):5086-5095.
doi: 10.21037/jtd.2020.04.18.

Role of immunotherapy and co-mutations on KRAS-mutant non-small cell lung cancer survival

Idoroenyi Amanam  1 , Isa Mambetsariev  1 , Rohan Gupta  1 , Srisairam Achuthan  2 , Yingyu Wang  2 , Rebecca Pharaon  1 , Erminia Massarelli  1 , Marianna Koczywas  1 , Karen Reckamp  1 , Ravi Salgia  1
Affiliations

Role of immunotherapy and co-mutations on KRAS-mutant non-small cell lung cancer survival

Idoroenyi Amanam et al. J Thorac Dis. 2020 Sep.

Abstract

Background: KRAS mutations reported in non-small cell lung cancer (NSCLC) represent a significant percentage of patients diagnosed with NSCLC. However, there still remains no therapeutic option designed to target KRAS. In an era with immunotherapy as a dominant treatment option in metastatic NSCLC, the role of immunotherapy in.

Kras: mutated patients is not clear.

Methods: Eligible patients diagnosed with NSCLC and found to have a KRAS mutation were identified in an institutional lung cancer database. Demographic, clinical, and molecular data was collected and analyzed.

Results: A total of 60 patients were identified for this retrospective analysis. Majority of patients were Caucasian (73%), diagnosed with stage IV (70%) adenocarcinoma (87%), and had a KRAS codon 12 mutation (78%). Twenty percent of patients were treated with immunotherapy. Median overall survival was 28 months in the cohort and patients who received immunotherapy were found to have better survival versus those who did not (33 vs. 22 months, P=0.31). Furthermore, there was an association between high survival and patients who received immunotherapy (P=0.007).

Conclusions: Patients with KRAS mutations have a unique co-mutation phenotype that requires further investigation. Immunotherapy seems to be an effective choice of treatment for KRAS positive patients in any treatment-line setting and yields better outcomes than conventional chemotherapy. The relationship between immunotherapy and KRAS mutations requires further studies to confirm survival advantage.

Keywords: KRAS; Lung cancer; co-mutations; immunotherapy; molecular testing.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd.2020.04.18). The authors have no conflicts of interest to declare. The series “Role of Precision Imaging in Thoracic Disease” was commissioned by the editorial office without any funding or sponsorship.

Figures

Figure 1
Figure 1
Patient characteristics. (A) Starburst plot of patient demographics according to their smoking history, age, and race; (B) distribution of KRAS mutant subtypes according to demographic groups by codons 12, 13, and 61.
Figure 2
Figure 2
Frequency of mutations in the KRAS cohort. (A) A heatmap of co-occurring mutations according to their mutation type including frameshift, exon loss, splice site, rearrangement, truncation, insertion, loss, deletion, amplification and substitution; (B) a heatmap showing up to 5 lines of therapy that the patients received during the course of their care. (C) the presence of co-occurring mutations in patients who were treated with immunotherapy versus patients who received no immunotherapy treatment. RET mutated co-occurrence was the only unique instance in immunotherapy patients.
Figure 3
Figure 3
KRAS mutations and outcomes. (A) Kaplan-Meier survival curve showing the complete OS of all of the 60 KRAS mutated patients with a median OS of 28 months; (B) Kaplan-Meier survival curve showing improved median OS of 33 months in patients who received immunotherapy versus 22 months in patients who did not received immunotherapy. OS, overall survival.
Figure S1
Figure S1
Immunotherapy and outcomes. In patients who received immunotherapy, there was observed a correlation with higher survival (P=0.007).
See this image and copyright information in PMC

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