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Khadeja Khan
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P36 - Pathology - Prognosis (ID 106)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P36.01 - KEAP1 and NRF2 Mutations in Hispanic and Non-Hispanic Patients with NSCLC: Clinicopathologic Characteristics and Prognosis. (ID 3712)
00:00 - 00:00 | Presenting Author(s): Khadeja Khan
- Abstract
Introduction
The KEAP1 is the third most mutated gene in NSCLC, activated in over 20% of both squamous and nonsquamous lung cancers. The KEAP1-NRF2 pathway regulates cellular detoxification and has been associated with poor prognosis, metastases, and treatment resistance in lung cancer. Notably, KEAP1 mutations have been also associated with lack of benefit to chemoimmunotherapy even in patients with good tumor predictive markers such as high PDL1 status. The incidence of KEAP1-NRF2 mutations and potential impact on treatment response for Hispanic patients with lung cancer has not been well characterized.
Methods
A total of 617 patients, 426 Non-Hispanic Whites (NWH) and 181 Hispanics, with a diagnosis of lung cancer and next generation sequencing information available in the University of Miami central genomic database were included. Incidence of KEAP1/NRF2 mutations, clinico-pathologic characteristics, common co-occurring mutations, and treatment response were analyzed. Progression Free Survival (PFS) was defined as the time from therapy initiation to radiologic progression. Overall survival (OS) was defined as time from diagnosis of metastatic disease to death or last contact.
Results
KEAP1/NRF2 gene mutation rate was 8.4% in our lung cancer cohort (52/617). Incidence of KEAP1/NRF2 mutations in Hispanics vs. NHW was (11%, 20/181) vs. (6.6%, 28/426), p= 0.066. Median age was 70 years (range 48-90). Patients presented with advanced (80%) and locally advanced disease (16%). There were 21 women, 30 light smokers (<1pack/day), 18 heavy smokers (>1pack/day) and 4 never smokers. Most patients had adenocarcinoma histology (82.7%), while 15.4% displayed squamous cell carcinoma. Most common co-occurring mutations were KRAS (36/52), TP53 (23/52), and STK11 (17/52). Of twenty-one patients with available PDL1 testing, the majority were PDL1 negative (16/21), and a positive PDL1 expression >1% was seen in 5 patients. There were 12 patients with intermediate and 8 patients with high tumor mutation burden. Median PFS for patients treated with platinum-based chemotherapy (n=21), chemoimmunotherapy (n=8) and immunotherapy (n=4) was 4.6, 2.9 and 2.0 months, respectively. Median OS for patients with KEAP1/NRF2 mutations was 16.6 months for all patients. Median OS was 20 months for Hispanics and 15.4 months for NHWs. (p=0.99).
Conclusion
KEAP1/NRF2 mutations portend poor prognosis and treatment resistance for both Hispanics and NHWs in this cohort. There was no statistical difference in prevalence of KEAP/NRF2 mutations and median overall survival for Hispanics when compared to NHWs with KEAP1/NRF2 mutations.
