In:
Cancer Chemotherapy and Pharmacology, Springer Science and Business Media LLC, Vol. 90, No. 2 ( 2022-08), p. 137-148
Abstract:
In RELAY, ramucirumab plus erlotinib (RAM + ERL) improved progression-free survival (PFS) in patients with untreated, metastatic, EGFR-mutated, non-small cell lung cancer (NSCLC). Here, we present the exposure–response relationship of RAM from RELAY. Methods Patients received ERL (150 mg/day) with either RAM (10 mg/kg) or placebo (PBO + ERL) every 2 weeks (Q2W). A population pharmacokinetic model predicted RAM minimum concentration after first dose ( C min,1 ), and at steady state ( C min, ss ), which were used to evaluate correlation between RAM exposure and efficacy and safety. The Kaplan–Meier method and Cox regression analyses were utilized to evaluate exposure–efficacy by C min,1 quartile. Exposure–safety was evaluated by assessing incidence rates for safety parameters by C min, ss quartile, with ordered categorical analysis used for ALT/AST only. Results Analyses included 216 patients treated with RAM + ERL and 225 patients treated with PBO + ERL. Adjusting for significant baseline covariates, no exposure–efficacy relationship was identified in RELAY: PFS hazard ratio (mean, 95% confidence intervals) for the C min,1 quartiles were 0.67 (0.45–0.99), 0.77 (0.53–1.12), 0.57 (0.38–0.84), and 0.50 (0.33–0.76). No apparent exposure–safety relationship was observed for selected safety endpoints, including Grade ≥ 3 hypertension, diarrhea, and dermatitis acneiform, and any grade hypertension, any grade and Grade ≥ 3 proteinuria, and any grade ALT/AST increased within liver failure/liver injury. Conclusions No association was observed between RAM exposure and response, suggesting that the RELAY regimen of RAM 10 mg/kg Q2W with ERL is an optimized, efficacious, and safe first-line treatment for patients with untreated, metastatic, EGFR-mutated NSCLC. Trial registration: ClinicalTrials.gov, NCT02411448.
Type of Medium:
Online Resource
ISSN:
0344-5704
,
1432-0843
DOI:
10.1007/s00280-022-04447-x
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
1458488-8
SSG:
15,3
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