Adjuvant Chemotherapy Guided by Molecular Profiling and Improved Outcomes in Early Stage, Non-Small-Cell Lung Cancer

Gavitt A Woodard; Sue X Wang; Johannes R Kratz; Clara T Zoon-Besselink; Chun-Yuan Chiang; Matthew A Gubens; Thierry M Jahan; Collin M Blakely; Kirk D Jones; Michael J Mann; David M Jablons

doi:10.1016/j.cllc.2017.05.015

Adjuvant Chemotherapy Guided by Molecular Profiling and Improved Outcomes in Early Stage, Non-Small-Cell Lung Cancer

Clin Lung Cancer. 2018 Jan;19(1):58-64. doi: 10.1016/j.cllc.2017.05.015. Epub 2017 May 31.

Affiliations

¹ Division of Adult Cardiothoracic Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA.
² Hong Kong Institute of Cell and Molecular Medicine, Hong Kong.
³ Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA.
⁴ Department of Pathology, University of California, San Francisco, San Francisco, CA.
⁵ Division of Adult Cardiothoracic Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA. Electronic address: david.jablons@ucsf.edu.

PMID: 28645632
DOI: 10.1016/j.cllc.2017.05.015

Abstract

Introduction: Many early stage non-small-cell lung cancer (NSCLC) patients who are not considered candidates for adjuvant treatment according to current guidelines do harbor occult metastasis, and have disease recurrence despite complete resection. Although National Comprehensive Cancer Network (NCCN) guidelines suggest clinicopathologic characteristics to identify high-risk patients for adjuvant intervention, molecular profiling more accurately predicts 5-year survival. Early evidence of clinical benefit from application of this molecular-based management strategy, however, has not been reported.

Patients and methods: An internationally validated, prognostic, 14-gene quantitative polymerase chain reaction expression assay was used to stratify risk prospectively in 100 consecutive patients with stage IA, IB, and IIA nonsquamous NSCLC. Kaplan-Meyer estimates, log rank analysis, and Cox regression were used to compare disease-free survival (DFS) between high-risk patients who did or did not elect adjuvant chemotherapy.

Results: Forty-eight patients (48%) were deemed high-risk according to molecular testing and 36 (36%) met NCCN high-risk criteria; risk designations were discordant in 34 (34%) of all patients. Estimated 5-year DFS was 48.9% among molecular high-risk patients who did not undertake adjuvant chemotherapy, 93.8% among untreated molecular low-risk patients, and 91.7% in molecular high-risk patients who did undergo chemotherapy (P = .004). In contrast, DFS was only 75.2% in untreated NCCN low-risk patients, and 61.9% in untreated NCCN high-risk patients (P = .183).

Conclusion: This prospective, nonrandomized study provides initial evidence that high-risk designation according to the 14-gene prognostic assay also predicts benefit from adjuvant chemotherapy for very early stage NSCLC, and further supports the superiority of molecular stratification over current NCCN criteria at identifying high-risk patients.

Keywords: Cisplatin-based adjuvant therapy; NCCN guidelines; Prognostic genetic signature; Risk stratification; Tumor genetic profile.

MeSH terms

Aged
Carcinoma, Non-Small-Cell Lung / drug therapy
Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Non-Small-Cell Lung / mortality
Chemotherapy, Adjuvant*
Drug Resistance, Neoplasm / genetics
Female
Humans
Lung Neoplasms / drug therapy
Lung Neoplasms / genetics*
Lung Neoplasms / mortality
Male
Neoplasm Staging
Pathology, Molecular / methods*
Practice Guidelines as Topic
Predictive Value of Tests
Prognosis
Risk
Survival Analysis