Survival outcome comparison of neoadjuvant and perioperative ICI-based therapies in patients with non-small cell lung cancer achieving MPR or pCR: a systematic review and meta-analysis

Abstract

Objectives: This study aims to compare the survival benefits of perioperative versus neoadjuvant immune checkpoint inhibitors (ICI)-based therapy in patients with resectable non-small cell lung cancer (NSCLC), focusing specifically on those who achieve major pathological response (MPR) or pathological complete response (pCR) following neoadjuvant ICI-based treatment.

Method: s: A systematic literature review was performed using PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases. A trial-level proportional meta-analysis was conducted to compare the two treatment modalities. A patient-level-based analysis was also conducted to obtain more evidence of different perioperative treatment regimens. Cox regression and accelerated failure time models were used to analyze the survival benefits in patients who achieved MPR or pCR for the proper treatment modality.

Results: Twenty-three studies were included in the trial-level proportional meta-analysis, wherein no statistical significance was observed in the 1-, 2-, and 3-year event-free survival (EFS) rates between patients with MPR and pCR receiving perioperative or neoadjuvant ICI-based therapy. The pooled median EFS (mEFS) was 40.1 and 32.1 months in patients with MPR receiving perioperative and neoadjuvant ICI-based therapies, respectively. Meanwhile, the pooled mEFS was 35.4 and 34.2 months in patients with pCR receiving perioperative and neoadjuvant ICI-based therapies, respectively. Multivariable Cox analysis showed that perioperative chemoimmunotherapy was a favorable prognostic factor compared with neoadjuvant chemoimmunotherapy in MPR patients (P = 0.038), but not in those with pCR (P = 0.408).

Conclusions: The EFS were similar among patients with NSCLC who received neoadjuvant and perioperative ICI-based treatment and achieved MPR or pCR. Multivariable Cox analysis indicated that perioperative chemoimmunotherapy was a favorable prognostic factor in patients who achieved MPR after neoadjuvant chemoimmunotherapy, but not in those who reached pCR.

Keywords: Accelerated failure time model; Major pathological response; Neoadjuvant chemoimmunotherapy; Non-small cell lung cancer; Pathological complete response; Perioperative chemoimmunotherapy.