The ORR, was 70.2% (95% CI: 56.5%-84.0%) met the pre-specified primary endpoint. There were 33 patients received surgery after neoadjuvant treatment. The MPR, pCR, pathological downstaging, and R0 rates were 9.1%, 3.0%, 57.6%, and 87.9%, respectively.
All participants (100%) experienced TRAEs, but no grade 5 TRAEs were observed. Grade 3/4 TRAEs occurred in 3 patients (6.4%), including diarrhea, interstitial pneumonia, and hepatic impairment, respectively. Discontinuation of Afatinib was observed in only one patient due to grade 4 diarrhea. The most common TRAEs during NAT were diarrhea (78.7%), rash (78.7%). Surgery-related complications occurred in 4 patients, including prolonged air leakage (9.1%) and bronchopleural fistula (3.0%). No surgery-related death occurred within 90 days postoperatively.
Efficacy Associated Molecular Characteristics for Afatinib
By IHC score, the expression of programmed cell death 1 ligand 1 (PD-L1) in primary tumor after NAT was significantly higher than those in baseline (p = 0.013), and this trend was validated in the evaluation of 5 paired samples before and after Afatinib treatment. By RNA-seq, “T cell receptor signaling” pathway was significantly enriched in responsive tumor samples, indicating T-cell activation and CD8+ T-cells infiltration after Afatinib treatment in responsive patients. Additionally, an increasing tendency of B-cells was observed after Afatinib treatment drainage lymph node samples in responsive patients. Finally, the changes in the tumor microenvironment (TME) between different response groups after Afatinib treatment were observed. Several immune cells including T-cells, cytotoxic lymphocytes, B-cells, and NK cells were higher in responders.
Afatinib as a single-agent neoadjuvant therapy for stage III EGFR-mutant NSCLC offers a favorable objective tumor response and has an acceptable toxicity profile in clinical practice. Dynamic changes in TME are observed, particularly in responders, which may have implications for identifying predictive markers for EGFR-TKI treatment and guiding the future clinical trials.
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