Dataset Information

Controversies in the treatment of RAS wild-type metastatic colorectal cancer.

ABSTRACT:

Objective

To provide guidance for the management of RAS wild-type (wt) metastatic colorectal cancer (mCRC) in daily practice.

Methods

Nominal group and Delphi techniques were used. A steering committee of seven experts analyzed the current management of RAS wt mCRC, through which they identified controversies, critically analyzed the available evidence, and formulated several guiding statements for clinicians. Subsequently, a group of 30 experts (the expert panel) was selected to test agreement with the statements, through two Delphi rounds. The following response categories were established in both rounds: 1 = totally agree, 2 = basically agree, 3 = basically disagree, 4 = totally disagree. Agreement was defined if ≥ 75% of answers were in categories 1 and 2 (consensus with the agreement) or 3 and 4 (consensus with the disagreement).

Results

Overall, 71 statements were proposed, which incorporated the following areas: (1) overarching principles; (2) tumor location; (3) triplets; (4) maintenance; (5) second-line and beyond treatments; (6) Rechallenge and liquid biopsy. After the two Delphi rounds, only six statements maintained a lack of clear consensus.

Conclusions

This document aims to describe the expert's attitude when dealing with several common clinical questions regarding patients with RAS wt mCRC.

SUBMITTER: Vera R

PROVIDER: S-EPMC7979622 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposePanitumumab 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.MethodsFrom 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.ResultsThe 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.ConclusionsMild-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 registrationClinicalTrials.gov; NCT00083616, NCT00089635, NCT00113763.