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Peter J. Kneuertz
P3.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 982)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Presentations: 1
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
P3.16-06 - Does Comprehensive Mutation Analysis Add Prognostic Value in Resected Early Stage Lung Adenocarcinoma? (ID 13410)
12:00 - 13:30 | Presenting Author(s): Peter J. Kneuertz
Recent efforts have been directed to enhance staging of non-small cell lung cancer by including common or targetable mutations. However, the predictive value of isolated mutations has been inconsistent between studies, possibly related to mutation interactions, confounding, and heterogeneous patient cohorts. We sought to determine the prognostic role of common mutations in resected early stage lung adenocarcinoma patients.a9ded1e5ce5d75814730bb4caaf49419 Method
Lung cancer mutation panel (PULMOL) using next generation sequencing was routinely obtained on tumors of 317 patients who underwent lobectomy and mediastinal lymphadenectomy for stage I-II adenocarcinoma from 2011-2017. Frequency of mutations was determined, and association with disease-free survival (DFS) and overall survival (OS) following complete resection was tested using Cox regression analysis.4c3880bb027f159e801041b1021e88e8 Result
At total of 248 (78%) patients had at least one mutation, 20% had two or more detected mutations. KRAS and EGFR genes were most frequently affected, in 39% and 24% of patients. EGFR mutations were almost exclusively seen in KRAS-negative patients, except for nine KRAS+/EGFR+ patients. TP53 mutation was the most common co-existing mutation in 59% of cases. Other frequent mutations were MET (6%), BRAF (5%), HRAS (4%), and ALK rearrangement (3%). KRAS mutation, and presence of two or more mutations were the only molecular predictors of decreased DFS and OS on univariate analysis (Figure). In a multivariate model, adjusting for pathologic stage, smoking status, histologic subtype, tumor factors and adjuvant therapy, KRAS and EGFR mutations were independently associated with decreased DFS (KRAS, HR 2.84 [95%CI:1.28-6.30]; EGFR, HR 3.24 [95%CI:1.40-7.48]) and OS (KRAS, HR 2.95 [95%CI:1.35-6.42]; EGFR, HR 2.87 [95%CI:1.25-6.61]).
Routine mutation analysis may yield important prognostic information in patients with completely resected early stage lung adenocarcinoma and may enhance staging when accounting for other known prognostic factors. KRAS mutation was the strongest predictor of worse survival. The prognostic value of EGFR should be further explored in KRAS-negative tumors.6f8b794f3246b0c1e1780bb4d4d5dc53
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