LRP1b Loss Predicts Sensitivity to Immunotherapy in Patients with NSCLC: An Analysis of the Phase III CheckMate-026 Randomized Trial.
무작위 임상시험
1/5 보강
PICO 자동 추출 (휴리스틱, conf 2/4)
유사 논문P · Population 대상 환자/모집단
환자: LRP1b alterations had a statistically significant improvement in objective response rate to nivolumab versus LRP1b wild-type patients (OR 3
I · Intervention 중재 / 시술
추출되지 않음
C · Comparison 대조 / 비교
추출되지 않음
O · Outcome 결과 / 결론
[CONCLUSIONS] LRP1b mutations are a candidate predictive biomarker for immune checkpoint inhibition versus chemotherapy in NSCLC. Further mechanistic characterization of LRP1b and prospective validation are warranted and might enable future clinical use.
[PURPOSE] Low-density lipoprotein receptor-related protein 1b (LRP1b) is a cell surface receptor, commonly altered in many cancers and associated with improved responses, progression-free survival (PF
- 표본수 (n) 18,369
- p-value P = 0.014
- p-value P = 0.0006
APA
Armstrong AJ, Dietz H, et al. (2025). LRP1b Loss Predicts Sensitivity to Immunotherapy in Patients with NSCLC: An Analysis of the Phase III CheckMate-026 Randomized Trial.. Clinical cancer research : an official journal of the American Association for Cancer Research, 31(24), 5198-5210. https://doi.org/10.1158/1078-0432.CCR-25-0952
MLA
Armstrong AJ, et al.. "LRP1b Loss Predicts Sensitivity to Immunotherapy in Patients with NSCLC: An Analysis of the Phase III CheckMate-026 Randomized Trial.." Clinical cancer research : an official journal of the American Association for Cancer Research, vol. 31, no. 24, 2025, pp. 5198-5210.
PMID
41065506
Abstract
[PURPOSE] Low-density lipoprotein receptor-related protein 1b (LRP1b) is a cell surface receptor, commonly altered in many cancers and associated with improved responses, progression-free survival (PFS), and overall survival with immune checkpoint inhibition.
[EXPERIMENTAL DESIGN] LRP1b alterations were determined by whole-exome sequencing and associated with PFS and objective response rates in patients with non-small cell lung cancer (NSCLC) in a post hoc analysis of the randomized controlled phase III CheckMate-026 (CM026) trial (NCT02041533) examining chemotherapy compared with nivolumab, adjusting for tumor mutational burden (TMB) and clinical features. We separately evaluated a deidentified nationwide (US-based) NSCLC clinico-genomic database for associations of LRP1b alterations and PFS with anti-PD-1 immunotherapy.
[RESULTS] In the clinico-genomic database cohort of patients with NSCLC (N = 18,369), LRP1b mutations were positively associated with TP53/KRAS alterations and inversely with EGFR/RET/MET/ERBB2 alterations and significantly improved PFS with PD-1 inhibition (n = 1,569; adjusted HR, 0.86; P = 0.014). In CheckMate-026, patients with LRP1b alterations had a statistically significant improvement in objective response rate to nivolumab versus LRP1b wild-type patients (OR 3.5; 95% confidence interval, 1.71-7.13; P = 0.0006) but not with chemotherapy (OR 0.63; 95% confidence interval, 0.32-1.26; P = 0.19), adjusting for TMB, age, gender, histology, smoking, and performance status. LRP1b mutations were associated with improved PFS with nivolumab (HR, 0.66; P = 0.04) but not chemotherapy (HR, 1.26; P = 0.25), also maintained in multivariate and TMB-adjusted analyses.
[CONCLUSIONS] LRP1b mutations are a candidate predictive biomarker for immune checkpoint inhibition versus chemotherapy in NSCLC. Further mechanistic characterization of LRP1b and prospective validation are warranted and might enable future clinical use.
[EXPERIMENTAL DESIGN] LRP1b alterations were determined by whole-exome sequencing and associated with PFS and objective response rates in patients with non-small cell lung cancer (NSCLC) in a post hoc analysis of the randomized controlled phase III CheckMate-026 (CM026) trial (NCT02041533) examining chemotherapy compared with nivolumab, adjusting for tumor mutational burden (TMB) and clinical features. We separately evaluated a deidentified nationwide (US-based) NSCLC clinico-genomic database for associations of LRP1b alterations and PFS with anti-PD-1 immunotherapy.
[RESULTS] In the clinico-genomic database cohort of patients with NSCLC (N = 18,369), LRP1b mutations were positively associated with TP53/KRAS alterations and inversely with EGFR/RET/MET/ERBB2 alterations and significantly improved PFS with PD-1 inhibition (n = 1,569; adjusted HR, 0.86; P = 0.014). In CheckMate-026, patients with LRP1b alterations had a statistically significant improvement in objective response rate to nivolumab versus LRP1b wild-type patients (OR 3.5; 95% confidence interval, 1.71-7.13; P = 0.0006) but not with chemotherapy (OR 0.63; 95% confidence interval, 0.32-1.26; P = 0.19), adjusting for TMB, age, gender, histology, smoking, and performance status. LRP1b mutations were associated with improved PFS with nivolumab (HR, 0.66; P = 0.04) but not chemotherapy (HR, 1.26; P = 0.25), also maintained in multivariate and TMB-adjusted analyses.
[CONCLUSIONS] LRP1b mutations are a candidate predictive biomarker for immune checkpoint inhibition versus chemotherapy in NSCLC. Further mechanistic characterization of LRP1b and prospective validation are warranted and might enable future clinical use.
MeSH Terms
Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Female; Male; Middle Aged; Mutation; Biomarkers, Tumor; Aged; Immunotherapy; Receptors, LDL; Prognosis; Nivolumab; Immune Checkpoint Inhibitors; Adult
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