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Mahir Khan
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P33 - Pathology - Immunotherapy Biomarker (ID 101)
- 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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P33.11 - Immunotherapy Outcomes in KRAS Mutated vs KRAS Wild-Type Advanced Lung Adenocarcinoma (ID 2006)
00:00 - 00:00 | Author(s): Mahir Khan
- Abstract
Introduction
KRAS is the most frequent oncogene driver mutation found in NSCLC in Western countries with the majority of KRAS mutations occurring in lung adenocarcinoma. Patients with KRAS-mutated NSCLC generally have poorer outcomes with chemotherapy and tyrosine kinase inhibitors. However, the predictive role of KRAS status in patients with NSCLC receiving immune checkpoint inhibitors (ICI) remains unclear. We sought to compare outcomes of advanced lung adenocarcinoma treated with ICI based on KRAS status.
Methods
From a single institution database of patients diagnosed with NSCLC from January 2016 to December 2018, we conducted a retrospective analysis of cases of stage IV lung adenocarcinoma who received treatment with ICI. A standard form was used to extract clinical characteristics including age, sex, race, treatment type, mutation status, PDL1 expression, disease control rate (DCR), partial response (PR), progression-free survival (PFS), and overall survival (OS).
Results
We identified 41 cases of stage IV lung adenocarcinoma treated with ICI, 8 were excluded due to insufficient data, 33 were included for analysis. The median age was 63 years, 19 (58%) of the patients were female, and 20 (61%) of the patients were black. 19 (58%) of the patients were treated with pembrolizumab, 7 (21%) with nivolumab, 5 (15%) with atezolizumab, and 2 (6%) with durvalumab. 16 patients (43%) had KRAS mutations, of which 3 (19%) had a concurrent MET mutation and 1 (6%) had a concurrent ALK mutation. The most common KRAS mutation was G12C with 7 (44%) cases. In the KRAS wild-type population, 10 (59%) patients had PDL1 expression >1% and DCR was 65% with 47% PR. In the KRAS mutated population, 14 (88%) of patients had PDL1 expression >1% and DCR was 75% with 63% PR. There was no difference in PFS (13.2mo vs 15.2mo, p = 0.47) or OS (16mo vs 16.7mo, p = 0.85) between KRAS wild-type vs KRAS mutated populations treated with ICI.
Conclusion
KRAS mutated advanced lung adenocarcinoma had similar PFS and OS compared with KRAS-wild type advanced lung adenocarcinoma treated with ICI despite numerically higher DCR and PDL1 expression in KRAS-mutants. Larger studies are needed to clarify the predictive role of KRAS mutational status in advanced lung adenocarcinoma treated with ICI.
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P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P76.33 - Concurrent EGFR and KRAS Mutations in Lung Adenocarcinoma: A Single Institution Case Series (ID 1668)
00:00 - 00:00 | Presenting Author(s): Mahir Khan
- Abstract
Introduction
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.
Methods
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.
Results
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.
Conclusion
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.
