Dataset Information

Exposure-response relationship of ramucirumab in patients with advanced second-line colorectal cancer: exploratory analysis of the RAISE trial.

ABSTRACT:

Purpose

To characterize ramucirumab exposure-response relationships for efficacy and safety in patients with metastatic colorectal cancer (mCRC) using data from the RAISE study.

Methods

Sparse pharmacokinetic samples were collected; a population pharmacokinetic analysis was conducted. Univariate and multivariate Cox proportional hazards models analyzed the relationship between predicted ramucirumab minimum trough concentration at steady state (C _min,ss) and survival. Kaplan-Meier analysis was used to evaluate survival from patients in the ramucirumab plus folinic acid, 5-fluorouracil, and irinotecan (FOLFIRI) treatment arm stratified by C _min,ss quartiles (Q). An ordered categorical model analyzed the relationship between C _min,ss and safety outcomes.

Results

Pharmacokinetic samples from 906 patients were included in exposure-efficacy analyses; samples from 905 patients were included in exposure-safety analyses. A significant association was identified between C _min,ss and overall survival (OS) and progression-free survival (PFS) (p < 0.0001 for both). This association remained significant after adjusting for baseline factors associated with OS or PFS (p < 0.0001 for both). Median OS was 11.5, 12.9, 16.4, and 16.7, and 12.4 months for ramucirumab C _min,ss Q1, Q2, Q3, Q4, and placebo group, respectively. Median PFS was 5.4, 4.6, 6.8, 8.5, and 5.2 months for ramucirumab C _min,ss Q1, Q2, Q3, Q4, and placebo group, respectively. The risk of Grade ≥3 neutropenia was associated with an increase in ramucirumab exposure.

Conclusions

Exploratory exposure-response analyses suggested a positive relationship between efficacy and ramucirumab exposure with manageable toxicities in patients from the RAISE study with mCRC over the ranges of exposures achieved by a dose of 8 mg/kg every 2 weeks in combination with FOLFIRI.

SUBMITTER: Cohn AL

PROVIDER: S-EPMC5573752 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Publications

Exposure-response relationship of ramucirumab in patients with advanced second-line colorectal cancer: exploratory analysis of the RAISE trial.

Cohn Allen Lee AL Yoshino Takayuki T Heinemann Volker V Obermannova Radka R Bodoky György G Prausová Jana J Garcia-Carbonero Rocio R Ciuleanu Tudor T Garcia-Alfonso Pilar P Portnoy David C DC Van Cutsem Eric E Yamazaki Kentaro K Clingan Philip R PR Polikoff Jonathon J Lonardi Sara S O'Brien Lisa M LM Gao Ling L Yang Ling L Ferry David D Nasroulah Federico F Tabernero Josep J

Cancer chemotherapy and pharmacology 20170725 3

<h4>Purpose</h4>To characterize ramucirumab exposure-response relationships for efficacy and safety in patients with metastatic colorectal cancer (mCRC) using data from the RAISE study.<h4>Methods</h4>Sparse pharmacokinetic samples were collected; a population pharmacokinetic analysis was conducted. Univariate and multivariate Cox proportional hazards models analyzed the relationship between predicted ramucirumab minimum trough concentration at steady state (C <sub>min,ss</sub>) and survival. Ka ...[more]

PMID: 28744667

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Project description:BackgroundNanoparticle albumin-bound paclitaxel (nab-PTX) has shown non-inferiority to paclitaxel (PTX) as second-line therapy for advanced gastric cancer (AGC) with fewer infusion-related reactions. The efficacy and safety of nab-PTX plus ramucirumab (RAM) was reported in a phase II trial; however, there is no randomized trial comparing this regimen with PTX plus RAM in patients with AGC. This retrospective study aimed to investigate the efficacy and safety of nab-PTX plus RAM versus PTX plus RAM in patients with AGC.MethodsThis study included patients with AGC who received nab-PTX plus RAM from September 2017 to January 2019 or PTX plus RAM from June 2015 to August 2017 as second-line chemotherapy in our hospital.ResultsA total of 113 and 138 patients who received nab-PTX plus RAM and PTX plus RAM, respectively, were analyzed. Median progression-free survival (PFS) was 3.9 months (95% confidence interval [CI]: 3.4-4.3) in the nab-PTX plus RAM group and 3.9 months (95% CI: 3.1-4.7) in the PTX plus RAM group (hazard ratio [HR]: 1.08; 95% CI: 0.83-1.40; P = 0.573). Median overall survival (OS) was 10.9 months (95% CI: 9.3-12.7) in the nab-PTX plus RAM group and 10.3 months (95% CI: 8.5-12.0) in the PTX plus RAM group (hazard ratio: 0.82; 95% CI: 0.61-1.10; P = 0.188). In patients with moderate/massive ascites, favorable outcomes for progression-free survival were observed in the nab-PTX plus RAM group compared with the PTX plus RAM group. Although anemia and fatigue (any grade) were more frequent in the nab-PTX plus RAM group, discontinuation of study treatment was not increased in the nab-PTX plus RAM group. There was no occurrence of hypersensitivity reaction in the nab-PTX plus RAM group, while two patients (1.4%) experienced grade 3 hypersensitivity reactions in the PTX plus RAM group.ConclusionsThe combination of nab-PTX plus RAM showed a similar efficacy and safety profile to PTX plus RAM as second-line treatment for patients with AGC.

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Dataset Information

Exposure-response relationship of ramucirumab in patients with advanced second-line colorectal cancer: exploratory analysis of the RAISE trial.

Purpose

Methods

Results

Conclusions

Publications

Exposure-response relationship of ramucirumab in patients with advanced second-line colorectal cancer: exploratory analysis of the RAISE trial.

Similar Datasets

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