P76.33 Concurrent EGFR and KRAS Mutations in Lung Adenocarcinoma: A Single Institution Case Series

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Lung adenocarcinomas with molecular mutations in both the EGFR and KRAS genes are a distinct group of patients. EGFR mutant lung cancers most commonly occur in nonsmokers, respond well to tyrosine kinase inhibitor (TKI) therapy, and have a higher relative overall survival rate. In contrast, KRAS mutant lung cancers occur more commonly in patients with smoking history, do not respond to TKI therapy, and have a lower overall relative survival rate. Historically, EGFR and KRAS mutations were thought to be mutually exclusive however in this case series we present multiple cases of lung adenocarcinoma with both EGFR and KRAS mutations. From a single institution database of patients with non-small cell lung cancer (NSCLC) from 2010 – 2019, cases with concurrent EGFR and KRAS mutations were extracted. Clinical characteristics of these patient cases were reviewed, including sex, age, smoking history, stage, treatment. In addition, pathologic features were evaluated including mutations and histologic features. Follow up data including treatment was recorded. From this database 92 out of 1025 (9%) patients had EGFR mutations and 4 out of the 92 EGFR mutated cancers had both KRAS and EGFR mutations (4%). All 4 patients were between ages 55 and 67, and 3 out of 4 (75%) patients were male. 2 out of 4 (50%) patients presented with metastatic disease, while the remainder presented with localized disease. All 4 patients had KRAS mutations on codon 12 (c.34_35delinsAA and p.G12N, c.35G>A and p.G12D, p.G12S, c.34G>A and p.G12S), and 2 of these had additional mutations on exon 13 (c.38_39delinsCT and p.G13A, and p.G13D). Two patients had EGFR exon 21 mutation (c.2573T>G, p.L858R, and c.2573T>G, p.L858R), one patient had exon 19 mutation (c.2240_2254del, p.L747_T751del), and one patient had exon 18 mutation (c.2180A>G, p.Y727C). Two patients had an additional MET amplification. One patient (25%) had PDL-1 expression >1%. One of the 2 patients with localized disease had lobectomy, while the other patient underwent radiation therapy. Both patients are alive and have no recurrence of disease. One of the 2 patients with metastatic disease underwent resection of brain metastases and SBRT, while the other underwent conservative management for bone metastases. Due to patient preference, neither patient received chemotherapy or immunotherapy. One patient died and the other remains in hospice care. Patients with concomitant EGFR and KRAS mutations may be a distinct subset of lung adenocarcinoma. EGFR and KRAS should no longer be considered mutually exclusive mutations. Clinical questions remain on the efficacy of treating concomitant EGFR and KRAS mutations with TKI therapy. Further studies are necessary to determine the most effective therapeutic strategies to address this unique subset of lung cancer patients. KRAS inhibitors are currently under study.