Adjuvant chemotherapy guided by molecular profiling and improved outcomes in early stage, non-small cell lung cancer

• Published in: Clinical lung cancer 2018-01, Vol.19 (1), p.58-64
• Main Authors: Woodard, Gavitt A., MD, Wang, Sue X., BS, Kratz, Johannes R., MD, Zoon-Besselink, Clara T., BS, Chiang, Chun-Yuan, MBBS, Gubens, Matthew A., MD, MS, Jahan, Thierry M., MD, Blakely, Collin M., MD, PhD, Jones, Kirk D., MD, Mann, Michael J., MD, Jablons, David M., MD
• Format: Article
• Language: English
• Subjects: Aged; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Chemotherapy, Adjuvant; Cisplatin-based adjuvant therapy; Drug Resistance, Neoplasm - genetics; Female; Hematology, Oncology and Palliative Medicine; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Male; NCCN guidelines; Neoplasm Staging; Pathology, Molecular - methods; Practice Guidelines as Topic; Predictive Value of Tests; Prognosis; Prognostic genetic signature; Pulmonary/Respiratory; Risk; Risk stratification; Survival Analysis; Tumor genetic profile
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2017.05.015

Structured Abstract Introduction Many early stage non-small cell lung cancer (NSCLC) patients who are not considered candidates for adjuvant treatment by current guidelines do harbor occult metastasis, and recur despite complete resection. While 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. Methods An internationally validated, prognostic, 14-gene quantitative PCR expression assay stratified risk prospectively in 100 consecutive patients with stage IA, IB and IIA non-squamous 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 by molecular testing and 36 met NCCN high-risk criteria; risk designations were discordant in 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 = 0.004). In contrast, DFS was only 75.2% in untreated NCCN low-risk patients, and 61.9% in untreated NCCN high-risk patients (P = 0.183). Discussion This prospective, non-randomized study provides initial evidence that high-risk designation by 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.