Perioperative immune checkpoint blockades improve prognosis of resectable non-small cell lung cancer.

OBJECTIVES: Immune checkpoint blockades (ICB) have been proven to improve prognosis of non-small cell lung (NSCLC) in the neoadjuvant setting, while whether its perioperative use could bring extra benefit remained unidentified. We aimed to demonstrate the prognostic benefit of perioperative ICB over preoperative-only use and investigate who could benefit from this "sandwich ICB therapy".

METHODS: Patients undergoing neoadjuvant therapy followed by surgery from 2018 to 2022 was retrospectively reviewed, and were divided into four groups based on the perioperative regimens: pre-ICB + post-CT, pre-ICB-only, pre-CT + post-ICB, and pre-CT-only. Treatment-related adverse events, surgical outcomes, therapeutic response, recurrence-free survival (RFS) and overall survival (OS) were compared.

RESULTS: Of 214 enrolled patients with preoperative therapy, 108 underwent immunochemotherapy and 106 underwent platinum-based chemotherapy. Compared with preoperative chemotherapy, preoperative immunochemotherapy was demonstrated with significantly higher major pathologic response (MPR, 57/108 vs 12/106) and pathologic complete response (pCR, 35/108 vs 4/106) rates with comparable adverse events. Regarding survival, perioperative ICB significantly improved the RFS (vs pre-CT-only HR, 0.15; 95% CI, 0.09-0.27; vs pre-ICB-only HR, 0.36; 95% CI, 0.15-0.88) and OS (vs pre-CT-only HR, 0.24; 95% CI, 0.08-0.68). In patients without MPR, perioperative ICB was observed to decrease the risk of recurrence (HR, 0.31; 95% CI 0.11-0.83) compared with preoperative ICB, and was an independent prognostic factor (p < 0.05) for RFS.

CONCLUSIONS: Perioperative ICB showed promising efficacy in improving pathological response and survival outcomes of resectable NSCLC. For patients without MPR after resection followed by preoperative ICB, sequential ICB treatment could be considered.