Real-world evidence of first-or second-line immune checkpoint inhibitors versus chemotherapy in advanced NSCLC: A prospective pragmatic multicenter Korean study

초록

Background: Immune checkpoint inhibitors (ICIs) have revolutionized advanced non-small cell lung cancer (NSCLC) treatment, but real-world evidence in Korean patients is limited. Methods: We conducted a nationwide, prospective, pragmatic multicenter study in Korea, enrolling patients with metastatic or locally advanced NSCLC treated between Jan 2017-Dec 2022. Patients who received ICI with or without chemotherapy (ICI+/-C) as first-line (since 2018) or second-line (since 2017-2018) were compared with historical controls who received chemotherapy alone. Co-primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety. Results: Among 1,501 patients, 1,219 received first-line therapy (ICI+/-C n=522, chemotherapy n=697). Median PFS was 8.1 vs. 5.1 months (HR 0.64, 95% confidence interval (CI) 0.56-0.74, p<0.0001); OS was 20.1 vs. 9.0 months (HR 0.49, 95% CI 0.41-0.58, p<0.0001). Both showed significant benefit with ICI+/-C. 1-year ORR was 40.6% vs. 11.6%. In the PD-L1 ≥50% subgroup, ICI+/-C significantly improved outcomes: PFS 11.9 vs. 5.0 months (HR 0.35, 95% CI 0.27-0.46) and OS 23.9 vs. 9.0 months (HR 0.42, 95% CI 0.32-0.55). At 12 months, PFS benefit was also seen in PD-L1 1–49% subgroup. OS benefit was consistent regardless of PD-L1 or smoking. EGFR wild-types and steroid non-users were associated with greater benefit from ICI therapy. In the second-line group (n=282), OS was significantly prolonged with ICI (10.8 vs. 5.9 months; HR 0.60, 95% CI 0.38-0.93) despite comparable PFS. Smokers had longer OS with ICI, without PFS gain. No PFS differences were observed by PD-L1 expression, EGFR mutation, or steroid use. Conclusions: This prospective, pragmatic real-world data confirms that ICI+/-chemotherapy significantly improved PFS and OS over chemotherapy alone in first-line NSCLC, across all levels of PD-L1 expression and smoking status. The survival benefit was notable in patients with EGFR wild-type tumors and steroid non-users. In the second-line setting, ICI treatment was associated with survival benefit despite no difference in PFS.