Perioperative toripalimab in non-small cell lung cancer: Clinical outcomes and safety from a large prospective real-world study.

Abstract

8010 Background: The phase III NEOTORCH trial demonstrated that perioperative toripalimab significantly improved event-free survival in stage IIIA–IIIB driver-gene-negative NSCLC, along with a favorable overall survival trend. However, the generalizability of randomized controlled trial (RCT) results to broader, more heterogeneous, real-world populations is uncertain. This study aimed to evaluate the effectiveness and safety of this regimen in routine clinical practice, providing essential evidence for treatment decisions. Methods: This nationwide, prospective, observational study in China consecutively enrolled patients with stage II-III NSCLC planned for perioperative treatment containing toripalimab. The primary endpoint was real-world event-free survival (rwEFS). Secondary endpoints included pathological complete response (pCR) rate, major pathological response (MPR) rate, objective response rate (ORR), R0 resection rate, real-world disease-free survival (rwDFS), real-world overall survival (rwOS), and safety. Results: Between December 9, 2024, and January 14, 2026, 1727 patients were enrolled from 221 tertiary and secondary hospitals across 28 provinces in China. Baseline characteristics: 82.8% male; 51.4% aged ≥65 years; ECOG PS 0/1/2 in 43.2%/54.4%/2.4%. Histology: 71.4% squamous, 18.3% nonsquamous, 10.3% NSCLC not otherwise specified. Clinical stage distribution: IIA (1.7%), IIB (10.4%), IIIA (52.8%), IIIB (33.0%), IIIC (2.1%). Of all enrolled patients, 542 (31.4%) were pending preoperative assessment. Surgery was not performed in 634 patients (36.7%); reasons included: other causes (64.9%), patient refusal (15.7%), surgical ineligibility (9.3%), disease progression (8.2%), and adverse events (1.9%). Ultimately, 551 patients (31.9%) underwent resection, with 503 having postoperative pathological assessment. The MPR rate was 67.0% (337/503) and the pCR rate was 39.6% (199/503). As of the data-cutoff, investigators reported 20 (1.2%) grade ≥3 or clinically significant treatment-emergent adverse events, with hematologic toxicities being most common. Immune-related adverse events were infrequent (four events: three grade 1–2 pneumonitis, one grade 3 rash). Conclusions: This is the largest prospective real-world study of perioperative immunotherapy in NSCLC to date. Its extensive geographic coverage and diverse patient population-including higher proportions of elderly patients, those with ECOG PS 1, and varied histologies-validate the effectiveness and manageable safety of perioperative toripalimab in routine practice beyond RCT settings. The significant pathological response rates observed support the clinical benefit of this regimen for a broad spectrum of stage II-III NSCLC patients, providing crucial evidence for real-world decision-making. Clinical trial information: ChiCTR2400091457.