Phase II trial of neoadjuvant camrelizumab and apatinib in resectable NSCLC: 3-year survival outcomes and dynamic circulating tumor DNA analyses.

BACKGROUND

Neoadjuvant camrelizumab plus apatinib has shown a promising major pathological response (primary endpoint) and pathological complete response (a secondary endpoint) in patients with resectable stage IIA-IIIB non-small-cell lung cancer (NSCLC) in a previous single-arm phase 2 trial. Here, we present the 3-year survival outcomes and potential prognostic factors with extended follow-up.

METHODS

This single-arm phase 2 study enrolled patients with resectable stage IIA-IIIB NSCLC (stage IIIB, T3N2 only, according to the eighth edition of the American Joint Commission on Cancer TNM staging classification). Patients received three cycles of neoadjuvant camrelizumab (200 mg, intravenously, q2w) and apatinib (250 mg, orally, qd, for 5 days followed by 2 days off) followed by surgery. At 4-8 weeks after surgery, patients received either adjuvant camrelizumab monotherapy for up to 12 cycles or other strategies at the investigator's discretion.

RESULTS

With the median follow-up of 42.6 months, the 3-year event-free survival (EFS), disease-free survival and overall survival were 58.9 % (95 % CI 46.9-69.1), 61.5 % (95 % CI 48.6-72.1), and 92.3 % (95 % CI 83.6-96.5), respectively. Among the pathological responses, residual viable tumors of ≤ 20 % were more strongly associated with improved EFS (HR 0.30, 95 % CI 0.13-0.72). Additionally, metabolic response on PET/CT after neoadjuvant treatment and ctDNA clearance during the perioperative period were significantly associated with improved EFS (HR 0.23 [95 % CI 0.08-0.62] and HR 0.23 [95 % CI 0.09-0.59], respectively).

CONCLUSIONS

Neoadjuvant camrelizumab plus apatinib provides a potential sustained benefit for patients with resectable stage IIA-IIIB NSCLC. Metabolic response on PET/CT and perioperative ctDNA clearance might be potential biomarkers for predicting survival.