Pharmacokinetics and safety of panitumumab in a patient with chronic kidney disease

Baas, Jara M; Guchelaar, Henk‐Jan; Gelderblom, Hans

doi:10.1007/s00280-017-3479-2

Cited by 10 publications

(9 citation statements)

References 10 publications

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“…However, our findings are limited to a small number of CKD model rats investigated herein. The clearance of other antibody drugs (bevacizumab and panitumumab) was similar between the subjects with normal renal function and patients with end-stage renal disease (Garnier-Viougeat et al, 2007;Krens et al, 2018). The difference in the outcomes between the present study and that from the previous study could be attributed to the presence of different types of CKD etiology or pathophysiology, such as the patients with end-stage renal disease undergoing hemodialysis being anuric.…”

Section: Discussioncontrasting

confidence: 53%

Augmented Clearance of Nivolumab Is Associated with Renal Functions in Chronic Renal Disease Model Rats

Taguchi

Hayashi

Ohuchi³

et al. 2021

Drug Metab Dispos

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The clinically approved dose of nivolumab is 240 mg Q2W. However, previous studies have shown that baseline nivolumab clearance (CL) is associated with treatment outcomes in patients with solid cancers, thus motivating researchers to identify prognostic factors and indices influencing nivolumab CL. This study used chronic kidney disease model rats to investigate whether chronic renal impairment affected nivolumab CL and explored the surrogate markers associated with nivolumab CL. We observed that the total CL for nivolumab (CL tot ) was approximately 1.42-times higher in chronic kidney disease model rats than that in sham rats with an increased urinary excretion. Additionally, CL tot showed positive correlation with renal CL for nivolumab (CL R ), but not with extrarenal CL. Furthermore, the baseline levels of creatinine, blood urea nitrogen, creatinine CL, and urinary albumin/creatine ratio based on laboratory data were also significantly correlated with CL R . Our findings suggest that nivolumab CL increases as renal function deteriorates due to an increased excretion of nivolumab in the urine; additionally, laboratory data reflecting renal function may be a feasible index to qualitatively estimate nivolumab CL prior to nivolumab treatment under conditions of renal impairment.

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Section: Discussioncontrasting

confidence: 53%

Augmented Clearance of Nivolumab Is Associated with Renal Functions in Chronic Renal Disease Model Rats

Taguchi

Hayashi

Ohuchi³

et al. 2021

Drug Metab Dispos

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“…By comparison, panitumumab is administered by weight at a dose of 6 mg/kg every 2 weeks; a 60-min infusion time is recommended for total doses ≤ 1,000 mg, and a 90-min infusion time is recommended for total doses > 1,000 mg (7). At this administration schedule, panitumumab's mean half-life is 7.5 days, with a minimum recorded mean serum concentration of 39 μg/mL (18). Studies have indicated that it takes 3 infusions of panitumumab to reach steady state (19), although similar information has not been published for cetuximab.…”

Section: Mode Of Action Against Egfrmentioning

confidence: 99%

Distinguishing Features of Cetuximab and Panitumumab in Colorectal Cancer and Other Solid Tumors

et al. 2019

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Cetuximab and panitumumab are two distinct monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR), and both are widely used in combination with chemotherapy or as monotherapy to treat patients with RAS wild-type metastatic colorectal cancer. Although often considered interchangeable, the two antibodies have different molecular structures and can behave differently in clinically relevant ways. More specifically, as an immunoglobulin (Ig) G1 isotype mAb, cetuximab can elicit immune functions such as antibody-dependent cell-mediated cytotoxicity involving natural killer cells, T-cell recruitment to the tumor, and T-cell priming via dendritic cell maturation. Panitumumab, an IgG2 isotype mAb, does not possess these immune functions. Furthermore, the two antibodies have different binding sites on the EGFR, as evidenced by mutations on the extracellular domain that can confer resistance to one of the two therapeutics or to both. We consider a comparison of the properties of these two antibodies to represent a gap in the literature. We therefore compiled a detailed, evidence-based educational review of the known molecular, clinical, and functional differences between the two antibodies and concluded that they are distinct therapeutic agents that should be considered individually during treatment planning. Available data for one agent can only partly be extrapolated to the other. Looking to the future, the known immune activity of cetuximab may provide a rationale for this antibody as a combination partner with investigational chemotherapy plus immunotherapy regimens for colorectal cancer.

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“…A reference line at y = 0 and local regression smoother trend lines have been included. Panels from the left: ETA3 versus body weight in kg (WT), ETA3 versus ALT concentration in U/L (AST), ETA3 versus AST concentration in U/L (ALT), and ETA3 versus creatinine clearance in mL/min (CL CR ) [11] showed that serum concentrations of panitumumab were within the ranges presented here for renal function subgroups. The patient's CL CR was 11 mL/min (severely impaired renal function); C max was 125 µg/mL (after the 11th and 12th infusions) and C trough was 37 µg/mL (just before the 12th infusion).…”

Section: Discussionmentioning

confidence: 64%

“…Here, we present data from three open-label phase 2 and phase 3 studies in patients with mCRC (NCT00083616, NCT00089635, and NCT00113763) to assess the effect of hepatic and renal impairment on exposure to panitumumab. Additionally, these results are comprehensively evaluated together with the limited real-world evidence available for the pharmacokinetics of panitumumab in patients with mCRC and severe hepatic or renal dysfunction, which is a rare patient population to study [ 11 , 12 ]. The objective of this manuscript was to provide observed panitumumab pharmacokinetics data from mCRC patients with mild-to-moderate hepatic dysfunction and mild-to-moderate renal dysfunction.…”

Section: Introductionmentioning

confidence: 99%

The impact of hepatic and renal function on panitumumab exposures in patients with metastatic RAS wild-type colorectal cancer

Liao

Prenen

Dutta

et al. 2021

Cancer Chemother Pharmacol

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Purpose Panitumumab is a human monoclonal antibody targeting the epidermal growth factor receptor for the treatment of wild-type RAS metastatic colorectal cancer (mCRC). Currently, no dedicated clinical studies have evaluated the effect of organ impairment on the pharmacokinetics of panitumumab. Here, we present data from late phase studies of panitumumab in patients with mCRC and analyses of the effect of hepatic or renal impairment on the exposure of panitumumab. Methods From three multicenter, open-label, phase 2 and phase 3 studies, 349 and 351 patients were included in hepatic and renal function subgroup analyses, respectively. Patients who received IV panitumumab and serum exposures were compared to patients with varying degrees of hepatic and renal organ dysfunction. Results The Cmax and Ctrough values for patients with mild (n = 119) and moderate (n = 4) hepatic impairment were within the range of serum concentrations of panitumumab for the normal hepatic function subgroup. The distributions of serum concentration of panitumumab in patients with mild (n = 85) or moderate (n = 19) renal impairment were similar to the serum concentrations of panitumumab in the normal renal function subgroup. Population pharmacokinetic modeling and covariate analysis results were also consistent with lack of any significant effect of renal or hepatic impairment on the pharmacokinetics of panitumumab. Additionally, real-world evidence from case studies of patients with mCRC and severe hepatic or renal impairment, which is a rare patient population to study, indicated lack of clinically relevant differences in exposure of panitumumab compared with patients with mCRC and normal hepatic or renal function. Conclusions Mild-to-moderate hepatic or renal dysfunction had no clinically meaningful impact on the pharmacokinetics of panitumumab in patients with mCRC. No dose adjustments for panitumumab are warranted in patients with mCRC with mild-to-moderate hepatic or renal dysfunction. Trial registration ClinicalTrials.gov; NCT00083616, NCT00089635, NCT00113763

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Pharmacokinetics and safety of panitumumab in a patient with chronic kidney disease

Cited by 10 publications

References 10 publications

Augmented Clearance of Nivolumab Is Associated with Renal Functions in Chronic Renal Disease Model Rats

Augmented Clearance of Nivolumab Is Associated with Renal Functions in Chronic Renal Disease Model Rats

Distinguishing Features of Cetuximab and Panitumumab in Colorectal Cancer and Other Solid Tumors

The impact of hepatic and renal function on panitumumab exposures in patients with metastatic RAS wild-type colorectal cancer

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