Mutation-Specific Response to Ramucirumab in Mutated Metastatic NSCLC: Insights From Circulating Cell-Free DNA Profiling (Liquid Biopsy Japan Addendum of RELAY Phase 3 Randomized Study).
OpenAlex 토픽 ·
Lung Cancer Treatments and Mutations
Colorectal Cancer Treatments and Studies
Cancer Genomics and Diagnostics
[INTRODUCTION] A previous analysis of the RELAY phase 3 liquid biopsy addendum demonstrated suppressed -activating mutation allele count, increased total cell-free DNA (cfDNA) concentration, and short
- 표본수 (n) 131
APA
Kazuto NISHIO, Kazuko SAKAI, et al. (2026). Mutation-Specific Response to Ramucirumab in Mutated Metastatic NSCLC: Insights From Circulating Cell-Free DNA Profiling (Liquid Biopsy Japan Addendum of RELAY Phase 3 Randomized Study).. JTO clinical and research reports, 7(5), 100963. https://doi.org/10.1016/j.jtocrr.2026.100963
MLA
Kazuto NISHIO, et al.. "Mutation-Specific Response to Ramucirumab in Mutated Metastatic NSCLC: Insights From Circulating Cell-Free DNA Profiling (Liquid Biopsy Japan Addendum of RELAY Phase 3 Randomized Study).." JTO clinical and research reports, vol. 7, no. 5, 2026, pp. 100963.
PMID
42006277
Abstract
[INTRODUCTION] A previous analysis of the RELAY phase 3 liquid biopsy addendum demonstrated suppressed -activating mutation allele count, increased total cell-free DNA (cfDNA) concentration, and shortened cfDNA fragment size with ramucirumab (RAM) plus erlotinib (ERL) versus placebo (PL) plus ERL in patients with mutated NSCLC. We report updated data by mutation subtypes.
[METHODS] Patients were randomized 1:1 to RAM plus ERL or PL plus ERL. Liquid biopsy samples were collected at baseline, during treatment, and at post-progression 30-day follow-up. activating mutation allele count, plasma cfDNA concentration, cfDNA fragment size, and treatment-emergent T790M were analyzed in patients with a valid baseline sample (N = 131) by mutation subgroups (ex19del; L858R).
[RESULTS] Within both ex19del and L858R subgroups, -activating mutation allele count decreased from baseline to cycle 4 in both treatment arms. Total cfDNA concentration significantly increased from baseline to cycle 4 ( 0.0001) and was sustained to follow-up in the RAM plus ERL arm within the L858R subgroup only. cfDNA fragment size decreased from baseline to cycle 4 in the RAM plus ERL arm within both subgroups. T790M rates in the RAM plus ERL and PL plus ERL arms were 22.2% (four of 18) and 52.9% (nine of 17), respectively, in the ex19del subgroup by cycle less than or equal to 155 and 31.8% (seven of 22) and 18.8% (three of 16), respectively, in the L858R subgroup by cycle less than or equal to 176.
[CONCLUSIONS] This updated analysis revealed differences in total cfDNA concentration and T790M mutation rates between ex19del and L858R. RAM plus ERL may exhibit greater antitumor effects on L858R, supporting the favorable survival benefits observed previously in patients with a L858R.
[METHODS] Patients were randomized 1:1 to RAM plus ERL or PL plus ERL. Liquid biopsy samples were collected at baseline, during treatment, and at post-progression 30-day follow-up. activating mutation allele count, plasma cfDNA concentration, cfDNA fragment size, and treatment-emergent T790M were analyzed in patients with a valid baseline sample (N = 131) by mutation subgroups (ex19del; L858R).
[RESULTS] Within both ex19del and L858R subgroups, -activating mutation allele count decreased from baseline to cycle 4 in both treatment arms. Total cfDNA concentration significantly increased from baseline to cycle 4 ( 0.0001) and was sustained to follow-up in the RAM plus ERL arm within the L858R subgroup only. cfDNA fragment size decreased from baseline to cycle 4 in the RAM plus ERL arm within both subgroups. T790M rates in the RAM plus ERL and PL plus ERL arms were 22.2% (four of 18) and 52.9% (nine of 17), respectively, in the ex19del subgroup by cycle less than or equal to 155 and 31.8% (seven of 22) and 18.8% (three of 16), respectively, in the L858R subgroup by cycle less than or equal to 176.
[CONCLUSIONS] This updated analysis revealed differences in total cfDNA concentration and T790M mutation rates between ex19del and L858R. RAM plus ERL may exhibit greater antitumor effects on L858R, supporting the favorable survival benefits observed previously in patients with a L858R.