In rNSCLC, pathological response after NEO-AT has been shown to be associated with long-term outcomes such as event-free survival (EFS) and overall survival (OS). Our objective was to systematically identify and meta-analyze the magnitude of the association from the available literature.
MEDLINE, EMBASE and CENTRAL were searched from database inception to March 2019. Eligible studies included randomized-controlled trials (RCTs), non-randomized trials, and cohorts of patients with rNSCLC treated with NEO-AT reporting OS or EFS by pathological complete response (pCR) status or major pathological response (MPR) status. Study design, baseline characteristics, treatment, and endpoints were extracted and validated. Kaplan-Meier curves were digitized and individual-patient data reconstructed to calculate hazard ratios (HR). HR for OS and HR for EFS by pathologic response status (i.e. pCR vs no-pCR; MPR vs no-MPR) were meta-analyzed using a random-effects model. Subgroup analyses according to endpoint definitions, population, treatment type, and study design were performed.
Among 7,200 records screened, 33 studies were included. Studies were RCTs (n=2), single-arm trials (n=3) or cohorts (n=28), with sample sizes from 26 to 1,750 patients. In all studies, NEO-AT consisted of platinum-based chemotherapy regimens ± radiotherapy. For OS by pCR status, the HRs ranged from 0.13 to 0.78, and the meta-analyzed HR across 21 studies (6,672 patients) was 0.49 (95% CI 0.43-0.56). For EFS by pCR status, the HRs ranged from 0.26 to 0.76, and the meta-analysed HR across 12 studies (2,297 patients) was 0.50 (95% CI 0.40-0.62). The magnitude of the HRs by MPR status were similar to the results by pCR status. Findings were consistent across subgroup analyses.
A strong association between pathological response and survival has been consistently shown in patient-level analyses across studies in the NEO-AT rNSCLC setting. Further research is needed to evaluate how treatment effects on the depth of pathological response relate to estimated treatment effects on survival-based endpoints.
Clinical trial identification
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All authors have declared no conflicts of interest.