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Imran Ahmad
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-29 - The Correlation Between K-Ras Mutant Subsets with TP53 Mutation and PD-L1 in Non-Small Cell Lung Cancer (NSCLC) (Now Available) (ID 2756)
10:15 - 18:15 | Author(s): Imran Ahmad
- Abstract
Background
Despite its role in non-small cell lung cancer (NSCLC), K-ras gene mutations are considered is a non-targetable with no established predictive value. And so far, programmed death ligand-1 (PD-L1) is the only approved predictive marker for immunotherapy in NSCLC patients and has been associated with smoking, while TP53 mutations has been linked to neoplasms with aggressive nature. Meanwhile, K-ras mutation has been identified with smoking and linked to aggressive NSCLC. Accordingly, we hypothesized that k-ras mutant NSCLC has higher PD-L1 expression which suggests an improved response to immunotherapy in these patients.
Method
The CARIS database from 2016 - 2018 was queried and patients with NSCLC were identified. PD-L1 antibody 22c3 ≥1% was considered positive. PD-L1 expression as well as k-ras and TP53 mutation status were analyzed and correlation between different variables were identified using ANOVA.
Result
Table 1: showing the percentage expression of PD-L1 in each K-ras mutation subtype K-ras mutation sub-type PD-L1 negative (n,%) PD-L1 positive (n,%) Total (n,%) G12V 205 (20.8%)
239 (18%) 444 (19.2%) G12D 142 (14.4%) 194 (14.6%) 336 (14.5%) G12A 56 (5.7%) 72 (5.4%) 128 (5.5%) G12C 337 (34.2%) 566 (42.7%) 903(39.1%) G13C 51 (5.2%) 46 (3.5%) 97 (4.2%) Q6H 54 (5.5%) 67 (5.1%) 121 (5.2%) G12R 18 (1.8%) 18 (1.4%) 36 (1.6%) G12S 18 (1.8%) 16 (1.2%) 34 (1.5%) Non-Specified 104 (10.6%) 108 (8.1%) 212 (9.2%) Total 985 (100%) 1326 (100%) 2311 (100%) We identified 8,471 patients with NSCLC. TP53 mutation was detected in 66% where k-ras mutation in 26.9%. Combined K-ras and TP53 mutations was detected in 12% where 71.48% were PD-L1 positive in this combined category. There was female predominance with a female to male ratio of 1.4:1. We looked for the eight main K-ras mutation subsets and G12C was the most common identified mutation. G12C was associated with a higher occurrence of PD-L1 positivity (42.7%), followed by G12V (18.0%) with a significant difference in PD-L1 expression among K-ras mutations subtypes with P value of 0.004. (table 1). PD-L1 expression in wild type K-ras tumors was 69.4% and although high, wild type K-ras cases showed higher percentage of PD-L1 expression negativity (76.2%).
Conclusion
Patients with G12C, amongst other k-ras mutation subsets, have higher occurrence of PD-L1 expression which is suggestive of improved response to immunotherapy. The subset of combined K-ras and p-53 mutations showed 71.48% positive PD-L1 expression.
