Molecular Risk Stratification is Independent of EGFR Mutation Status in Identifying Early-Stage Non-Squamous Non-Small Cell Lung Cancer Patients at Risk for Recurrence and Likely to Benefit From Adjuvant Chemotherapy

Gavitt A Woodard; Johannes R Kratz; Greg Haro; Matthew A Gubens; Collin M Blakely; Kirk D Jones; Michael J Mann; David M Jablons

doi:10.1016/j.cllc.2021.08.008

Molecular Risk Stratification is Independent of EGFR Mutation Status in Identifying Early-Stage Non-Squamous Non-Small Cell Lung Cancer Patients at Risk for Recurrence and Likely to Benefit From Adjuvant Chemotherapy

Clin Lung Cancer. 2021 Nov;22(6):587-595. doi: 10.1016/j.cllc.2021.08.008. Epub 2021 Aug 20.

Authors

Gavitt A Woodard¹, Johannes R Kratz², Greg Haro², Matthew A Gubens³, Collin M Blakely³, Kirk D Jones⁴, Michael J Mann², David M Jablons²

Affiliations

¹ Department of Surgery, Division of Adult Cardiothoracic Surgery, University of California, San Francisco, CA. Electronic address: gavitt.woodard@yale.edu.
² Department of Surgery, Division of Adult Cardiothoracic Surgery, University of California, San Francisco, CA.
³ Division of Hematology and Oncology, University of California, San Francisco, CA.
⁴ Department of Pathology, University of California, San Francisco, CA.

PMID: 34544620
DOI: 10.1016/j.cllc.2021.08.008

Abstract

Background: A clinically-certified gene expression profile improved survival in a cohort of stage I-IIA NSCLC patients by identifying those likely to benefit from adjuvant intervention. EGFR mutation status has not provided this type of predictive risk discrimination in stage IA NSCLC, and overtreatment of low-risk stage IB patients may have limited the overall benefit seen recently in the adjuvant application of a third-generation TKI. We compared EGFR mutation data to molecular risk stratification in a prospective, early-stage cohort.

Materials and methods: Two hundred fifty eligible stage I-IIA non-squamous NSCLC patients underwent prospective molecular risk stratification by the 14-gene prognostic assay. Platinum doublet adjuvant chemotherapy (AC) was recommended for molecular high-risk (MHR). Differences in freedom from recurrence (FFR) and disease-free survival (DFS) were evaluated.

Results: At 29 months, prospective molecular testing yielded an estimated FFR of 94.6% and 72.4% in low-risk and untreated MHR patients, respectively, and 97.0% among MHR patients receiving AC (P < .001). In contrast, there was no association between EGFR status and recurrence, while molecular risk predicted survival and response to AC within both the EGFR mutation(+) and mutation(-) populations. Sixty-seven percent of EGFR(+) and 49% of EGFR(-) patients were molecular low-risk.

Conclusion: This prospective study demonstrates the utility of the 14-gene assay independent of EGFR mutation. Basing adjuvant intervention in early-stage NSCLC on EGFR status alone may undertreat up to 51% of EGFR(-) patients likely to benefit from adjuvant intervention, and overtreat as many as 67% of EGFR(+) patients more likely to be free of residual disease.

Keywords: Lung adenocarcinoma; Plainum-doublet chemotherapy; Prognostic/predictive risk stratification; Stage IA; Surgery.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Carcinoma, Non-Small-Cell Lung / pathology*
Chemotherapy, Adjuvant*
Early Detection of Cancer
ErbB Receptors / genetics*
Female
Humans
Lung Neoplasms / pathology*
Male
Mutation / genetics*
Neoplasm Staging*
Prospective Studies
Risk Assessment / methods*

Substances

ErbB Receptors