Effect of ALK-TKI in ALK-Rearranged versus ALK-Rearranged With PD-L1 Positive NSCLC: A Target Trial Emulation Study
Author(s)
Yijin Qiu, MS1, Yexin Chen, student2, Yunwu Zhong, student2, Tiantian Zhang, professor2.
1PhD.Student, Jinan University, Guangzhou, China, 2Jinan University, Guang zhou, China.
1PhD.Student, Jinan University, Guangzhou, China, 2Jinan University, Guang zhou, China.
OBJECTIVES: ALK inhibitors are standard treatment for ALK-positive NSCLC, but their efficacy in patients with concurrent PD-L1 expression remains uncertain. This study compared outcomes of first-line alectinib in ALK-rearranged NSCLC patients with or without PD-L1 positivity.
METHODS: This retrospective study conducted target trial emulation to compared progression-free survival (PFS) and overall survival (OS) in patients had ALK-rearranged NSCLC with or without PD-L1 positivity receiving alectinib, based on the Flatiron Health database (2004-2025). Inverse probability of treatment weighting (IPTW) balanced baseline characteristics. Time-to-first-event analysis was performed using Cox proportional hazards and Kaplan-Meier survival analysis, with the hazard ratio and 95% confidence interval calculated.
RESULTS: 320 ALK-rearranged NSCLC patients were enrolled, with 75 in PD-L1-negative group (average age was 60.7[30.0-85.0] years; 39 were male; 54 were White, 4 were Black or African American, 5 were Asian, and 12 were other races; 24 had history of smoking; 51 were ECOG performance status 0 through 1) and 245 in PD-L1-positive group (average age was 61.4[28.0-85.0] years; 103 were male; 147 were White, 16 were Black or African American, 21 were Asian, and 61 were other races; 103 had history of smoking; 150 were ECOG performance status 0 through 1). After IPTW, median 5-year PFS was 30.6 months (PD-L1-negative) versus 33.8 months (PD-L1-positive). Median 5-year OS was not reached in PD-L1-negative patients versus 50.1 months in PD-L1-positive patients. PD-L1-negative status showed a non-significant trend toward improved OS (HR 0.75, 95% CI 0.44-1.26, p=0.274) with similar PFS between groups (HR 1.01, 95% CI 0.68-1.51, p=0.955). Subgroup analysis revealed that among patients aged <60 years, PD-L1-negative status was associated with significantly better OS outcomes
CONCLUSIONS: Alectinib as first-line treatment in ALK-positive NSCLC with PD-L1 positivity demonstrates no significant difference in efficacy compared to ALK-positive and PD-L1 negative patients, and it remains an effective treatment option.
METHODS: This retrospective study conducted target trial emulation to compared progression-free survival (PFS) and overall survival (OS) in patients had ALK-rearranged NSCLC with or without PD-L1 positivity receiving alectinib, based on the Flatiron Health database (2004-2025). Inverse probability of treatment weighting (IPTW) balanced baseline characteristics. Time-to-first-event analysis was performed using Cox proportional hazards and Kaplan-Meier survival analysis, with the hazard ratio and 95% confidence interval calculated.
RESULTS: 320 ALK-rearranged NSCLC patients were enrolled, with 75 in PD-L1-negative group (average age was 60.7[30.0-85.0] years; 39 were male; 54 were White, 4 were Black or African American, 5 were Asian, and 12 were other races; 24 had history of smoking; 51 were ECOG performance status 0 through 1) and 245 in PD-L1-positive group (average age was 61.4[28.0-85.0] years; 103 were male; 147 were White, 16 were Black or African American, 21 were Asian, and 61 were other races; 103 had history of smoking; 150 were ECOG performance status 0 through 1). After IPTW, median 5-year PFS was 30.6 months (PD-L1-negative) versus 33.8 months (PD-L1-positive). Median 5-year OS was not reached in PD-L1-negative patients versus 50.1 months in PD-L1-positive patients. PD-L1-negative status showed a non-significant trend toward improved OS (HR 0.75, 95% CI 0.44-1.26, p=0.274) with similar PFS between groups (HR 1.01, 95% CI 0.68-1.51, p=0.955). Subgroup analysis revealed that among patients aged <60 years, PD-L1-negative status was associated with significantly better OS outcomes
CONCLUSIONS: Alectinib as first-line treatment in ALK-positive NSCLC with PD-L1 positivity demonstrates no significant difference in efficacy compared to ALK-positive and PD-L1 negative patients, and it remains an effective treatment option.
Conference/Value in Health Info
2025-09, ISPOR Real-World Evidence Summit 2025, Tokyo, Japan
Value in Health Regional, Volume 49S (September 2025)
Code
RWD134
Topic Subcategory
Health & Insurance Records Systems
Disease
SDC: Oncology