Individual chemotherapy based on the determination of molecular biomarkers of chemosensitivity is a new way to treat patients with NSCLC. Promising markers for chemosensitivity are monoresistance genes such as BRCA1, RRM1, ERCC1, TOP1, TOP2α, TUBB3, TYMS, and ABCC5.
We enrolled and analyzed 62 patients with stage III NSCLC. All the patients have received 2 courses of neoadjuvant chemotherapy vinorelbine/carboplatin and surgery. Then patients were randomly assigned (1:1 ratio) to either the personalized adjuvant chemotherapy arm (main group) or the adjuvant chemotherapy vinorelbine/carboplatin arm (control group). In the main group, carboplatin-containing doublets were assigned based on monoresistance gene expression levels ABCC5, RRM1, ERCC1, BRCA1, TOP1, TOP2α, TUBB3 and TYMS. RNA was extracted from tumor after neoadjuvant chemotherapy using “RNeasy Plus Mini Kit” (QIAGEN, Germany). The analysis of monoresistance genes expression was done by qRT-PCR method. A χ2 test was used to analyze gene expression in relation to clinicopathological parameters. The survival rates were calculated by the Kaplan-Meier method.
The follow-up period was 4 - 76 months. In the main group, the disease progression was observed in 6 patients (19.4%), in the control group - 15 patients (48.4%). Three-year disease-free survival in the main group was 80.7% (median DFS not achieved), in the control group - 51.6%, median DFS - 34 months (HR: 2.56, 95% CI: 1.09 - 6,03); differences are statistically significant: Log-Rank test χ2=4.196, p = 0.041. There was no difference in three-year overall survival (main group: 87.1%, control group: 67.7%, HR: 2.27, 95% CI: 0.79 - 6,47).
Personalized postoperative chemotherapy based on the determination of monoresistance gene expression after neoadjuvant chemotherapy allows significant increase of patients 3-year disease-free survival by 29.1%.
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Legal entity responsible for the study
Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia.
Has not received any funding.
All authors have declared no conflicts of interest.