COMPARATIVE EFFICACY AND SAFETY OF FIRST-LINE ALK INHIBITORS FOR ADVANCED ALK-POSITIVE NON-SMALL CELL LUNG CANCER: A SYSTEMATICREVIEW AND NETWORK META-ANALYSIS...
Author(s)
Mingye Zhao, PhD1, Zhou Ke Jia, Master2, Yunong Jiang, Master2, Yutong Xu, Master1, Ying Xing, Master1, Wenxi Tang, PhD2.
1Nanjing, China Pharmaceutical University, Nanjing, China, 2China Pharmaceutical University, Nanjing, China.
1Nanjing, China Pharmaceutical University, Nanjing, China, 2China Pharmaceutical University, Nanjing, China.
OBJECTIVES: Several anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are available for first-line treatment of advanced ALK-positive non-small cell lung cancer (NSCLC), but head-to-head comparative evidence remains limited. We conducted a network meta-analysis (NMA) to compare the efficacy and safety of first-line ALK-TKIs.
METHODS: A systematic MEDLINE search identified randomized controlled trials evaluating first-line therapies for advanced or metastatic ALK-positive NSCLC. Nine eligible trials were included. Independent review committee-assessed progression-free survival (PFS) and overall survival (OS) were analyzed using hazard ratios (HRs) and restricted mean survival time (RMST). Safety outcomes included any-grade adverse events (AEs), grade ≥3 AEs, selected toxicities, treatment discontinuation, and dose reduction.
RESULTS: Nine randomized controlled trials were included, covering 1 first-generation, 6 second-generation, and 1 third-generation ALK TKIs, plus chemotherapy. PFS findings were consistent between HR- and RMST-based analyses. Compared with conteltinib, lorlatinib (HR 0.30, 95% CrI 0.20-0.47) and iruplinalkib (0.54, 0.34-0.86) showed significantly improved PFS, whereas chemotherapy (3.53, 2.47-5.04), ceritinib (1.94, 1.23-3.05), and crizotinib (1.59, 1.25-2.01) showed significantly worse PFS. No significant PFS differences were observed between conteltinib and alectinib, brigatinib, ensartinib, or envonalkib. For OS, neither HR- nor RMST-based analyses identified significant differences between conteltinib and any comparator. Conteltinib was associated with a significantly lower risk of grade ≥3 AEs than brigatinib (OR 3.00, 95% CrI 1.59-5.62), crizotinib (1.67, 1.13-2.46), envonalkib (2.38, 1.26-4.48), iruplinalkib (1.93, 1.06-3.55), and lorlatinib (2.82, 1.55-5.17). Conteltinib showed the most favorable profile among all TKIs for treatment discontinuation and dose reduction, and analyses of hepatic and hematologic toxicities supported its favorable tolerability profile.
CONCLUSIONS: Conteltinib demonstrated PFS comparable to commonly used first-line second-generation ALK-TKIs. No significant OS differences were observed across treatments. Conteltinib showed a favorable safety and tolerability profile, particularly for grade ≥3 AEs, treatment discontinuation, and dose reduction, supporting its role as a first-line treatment option for advanced ALK-positive NSCLC.
METHODS: A systematic MEDLINE search identified randomized controlled trials evaluating first-line therapies for advanced or metastatic ALK-positive NSCLC. Nine eligible trials were included. Independent review committee-assessed progression-free survival (PFS) and overall survival (OS) were analyzed using hazard ratios (HRs) and restricted mean survival time (RMST). Safety outcomes included any-grade adverse events (AEs), grade ≥3 AEs, selected toxicities, treatment discontinuation, and dose reduction.
RESULTS: Nine randomized controlled trials were included, covering 1 first-generation, 6 second-generation, and 1 third-generation ALK TKIs, plus chemotherapy. PFS findings were consistent between HR- and RMST-based analyses. Compared with conteltinib, lorlatinib (HR 0.30, 95% CrI 0.20-0.47) and iruplinalkib (0.54, 0.34-0.86) showed significantly improved PFS, whereas chemotherapy (3.53, 2.47-5.04), ceritinib (1.94, 1.23-3.05), and crizotinib (1.59, 1.25-2.01) showed significantly worse PFS. No significant PFS differences were observed between conteltinib and alectinib, brigatinib, ensartinib, or envonalkib. For OS, neither HR- nor RMST-based analyses identified significant differences between conteltinib and any comparator. Conteltinib was associated with a significantly lower risk of grade ≥3 AEs than brigatinib (OR 3.00, 95% CrI 1.59-5.62), crizotinib (1.67, 1.13-2.46), envonalkib (2.38, 1.26-4.48), iruplinalkib (1.93, 1.06-3.55), and lorlatinib (2.82, 1.55-5.17). Conteltinib showed the most favorable profile among all TKIs for treatment discontinuation and dose reduction, and analyses of hepatic and hematologic toxicities supported its favorable tolerability profile.
CONCLUSIONS: Conteltinib demonstrated PFS comparable to commonly used first-line second-generation ALK-TKIs. No significant OS differences were observed across treatments. Conteltinib showed a favorable safety and tolerability profile, particularly for grade ≥3 AEs, treatment discontinuation, and dose reduction, supporting its role as a first-line treatment option for advanced ALK-positive NSCLC.
Conference/Value in Health Info
2026-09, ISPOR Asia Pacific 2026, Bangkok, Thailand
Value in Health, Volume 55, Issue S1
Code
CO15
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment
Disease
SDC: Oncology