Abstract 1164P
Background
Neo-adjuvant therapy (NAT) could increase the pathological complete response (pCR) rate of patients with surgical NSCLC, which may improve long-term survival. However, the methods for predicting the efficacy of NAT and postoperative recurrence monitoring are still lacking. Analysis of ctDNA may provide a solution.
Methods
To design a ctDNA monitor for NSCLC, we started with including all exons covering known driver genes from the COSMIC database. Then, using in-house sequencing data from 1577 patients with NSCLC profiled by 3D medicines, we applied an iterative algorithm to maximize the coverage of patients while controlling panel size. NATs for patients included chemotherapy (C), nivolumab plus chemotherapy (NC) or nivolumab plus ipilimumab (NI). Blood samples were collected at baseline, during the NAT phase and the postoperative phase. Categorical variables were compared by Fisher exact test. Kaplan-Meier curves of recurrence-free survival (RFS) was analyzed by a Log-rank test with the hazard ratio (HR) determined from a Cox proportional hazards regression model with SPSS 24.0. Significant difference was defined as p<0.05.
Results
A total of 25 patients were included for analysis, including 20 (80%) males and five (20%) females. Eight patients received C, 12 patients received NC and five patients received NI as NATs, respectively. 22 patients received surgery and were followed for up to two years. A total of 117 blood samples were sequenced. Patients without detectable ctDNA (ctDNA-) after NATs achieved better ORR (100% vs. 53.3%, p=0.02), pCR (55.6% vs. 15.4%, p=0.07) and major pathological response (MPR) (66.7% vs 23.1%, p=0.08) compared with patients with detectable ctDNA (ctDNA+). Patients with ctDNA- at one-week after surgeries showed an improved RFS (not reach (NR) vs. 8.47 months; HR, 5.37; 95%CI, 1.27-22.67; p=0.01) compared with patients with ctDNA+. Patients with ctDNA- at three-month after surgeries showed an even better RFS (NR vs. 8.63 months; HR, 13.01; CI, 1.49-113.23; p<0.01) than patients with ctDNA+.
Conclusions
Analysis of ctDNA could effectively predict the efficacy of neo-adjuvant therapy and monitor recurrence.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
L. Cui: Financial Interests, Institutional, Full or part-time Employment: 3D Medicines. S. Song: Financial Interests, Institutional, Full or part-time Employment: 3D Medicines. J. Wang: Financial Interests, Institutional, Full or part-time Employment: 3D Medicines. X. Zhang: Financial Interests, Institutional, Full or part-time Employment: 3D Medicines. X. Zhao: Financial Interests, Institutional, Full or part-time Employment: 3D Medicines. All other authors have declared no conflicts of interest.