Neoadjuvant camrelizumab (an anti-PD-1 antibody) plus chemotherapy or apatinib (a VEGFR-2 inhibitor) for initially unresectable stage II-III non-small-cell lung cancer: a multicentre, two-arm, phase 2 exploratory study

Abstract

This multicentre, two-arm, phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II-III non-small-cell lung cancer (NSCLC). Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks (arm A) or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily (arm B), for 2-4 cycles, followed by surgery. The primary endpoint was major pathological response (MPR) rate. Thirty patients in arm A and 21 in arm B were enrolled. Surgery rates were 50.0% (15/30) in arm A and 42.9% (9/21) in arm B, with all patients achieving R0 resections. Of these patients, the MPR and pathological complete response rates were both 20.0% (95% CI 4.3-48.1) in arm A and were 55.6% (95% CI 21.2-86.3) and 11.1% (95% CI 0.3-48.2) in arm B, respectively. The corresponding objective response rates were 33.3% (95% CI 11.8-61.6) and 55.6% (95% CI 21.2-86.3). With a median follow-up of 22.4 months (95% CI 19.0-26.0), the median event-free survival was not reached (NR; 95% CI 13.6-NR) in arm A and 16.8 months (95% CI 8.6-NR) in arm B. Grade 3 or above treatment-related adverse events occurred in eight (26.7%) patients in arm A and three (14.3%) in arm B. Biomarker analysis showed baseline TYROBP expression was predictive of treatment response in arm B. Neoadjuvant camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II-III NSCLC.

Fig. 1

Patient flowchart

Fig. 2

Kaplan–Meier curves for event-free survival (EFS) and overall survival (OS). EFS and OS were assessed in arm A (a, c) and arm B (b, d) in the full analysis population

Fig. 3

Transcriptomic analysis of baseline tumor samples in arm B. Differential expression analysis (a) and GSEA (b) in tumor samples from responders (n = 2) and non-responders (n = 11). c Receiver operating characteristic plots of the predictive values of TYROBP and PILRA expression for response to neoadjuvant treatment. Patients with high TYROBP expression presented with better OS (d) and EFS (e). f Boxplot showing immunescore in baseline tumor samples from responders versus non-responders. g Increasing CD8 + T cells in baseline tumor samples from responders. h Increasing T cell effectors’ expression in baseline tumor samples from responders. Boxplots showing fraction of TCR reads (i) and unique TCR CDR3 (j) in baseline tumor samples from responders versus non-responders. Two-sided Wilcoxon rank sum test was used for comparison in figure (f–j). *P < 0.05; **P < 0.01; ***P < 0.001. ns, not significant