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Panitumumab in Metastatic Colorectal Cancer: The Importance of Tumour RAS Status.

Peeters M, Karthaus M, Rivera F, Terwey JH, Douillard JY - Drugs (2015)

Bottom Line: Continued cycles of hypothesis generation and biomarker testing in retrospective, prospective-retrospective and prospective analyses from studies of the epidermal growth factor (EGFR)-targeted monoclonal antibodies (mAbs), panitumumab and cetuximab, have resulted in improved patient selection in mCRC.Here, we review key clinical data for panitumumab in mCRC across the lines of treatment, assessing in detail the impact of more comprehensive RAS selection on patient outcomes.Panitumumab data across first- to third-line therapy consistently demonstrate that by testing tumour RAS status, it is possible to select patients more likely to benefit from treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium, Marc.Peeters@uza.be.

ABSTRACT
Tumour biomarker status is being used more and more frequently to guide treatment decisions in patients with metastatic colorectal cancer (mCRC). Continued cycles of hypothesis generation and biomarker testing in retrospective, prospective-retrospective and prospective analyses from studies of the epidermal growth factor (EGFR)-targeted monoclonal antibodies (mAbs), panitumumab and cetuximab, have resulted in improved patient selection in mCRC. Initial data suggested EGFR-targeted mAb treatment should be limited to patients with KRAS exon 2 wild-type (WT) tumours, but the availability of tumour samples from large phase III studies permitted evaluation of additional potential biomarkers of activity for these agents. Subsequent analyses further refined the target population to those patients whose tumours were WT for KRAS and NRAS exons 2, 3 and 4 (i.e., those with RAS WT status). Here, we review key clinical data for panitumumab in mCRC across the lines of treatment, assessing in detail the impact of more comprehensive RAS selection on patient outcomes. Panitumumab data across first- to third-line therapy consistently demonstrate that by testing tumour RAS status, it is possible to select patients more likely to benefit from treatment.

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The cycle of hypothesis generation/testing to refine the target metastatic colorectal cancer population for panitumumab treatment. ASCO American Society of Clinical Oncology, NCCN National Comprehensive Cancer Network, NGS next-generation sequencing, PCR polymerase chain reaction, PRA prospective–retrospective analysis
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Related In: Results  -  Collection


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Fig1: The cycle of hypothesis generation/testing to refine the target metastatic colorectal cancer population for panitumumab treatment. ASCO American Society of Clinical Oncology, NCCN National Comprehensive Cancer Network, NGS next-generation sequencing, PCR polymerase chain reaction, PRA prospective–retrospective analysis

Mentions: Tumour biomarker status is increasingly used to guide treatment decisions in patients with cancer and has been a rapidly developing area of research in metastatic colorectal cancer (mCRC). Improved patient selection through the use of biomarkers is likely to be particularly beneficial in mCRC because of the heterogeneity of response amongst these patients and the costs and toxicities associated with the available targeted therapies [2]. Approximately 27–43 % of mCRC tumours harbour KRAS exon 2 mutations that lead to constitutive activation of downstream signalling pathways [3]. Results of several uncontrolled [4, 5] and phase II [6] studies led to the hypothesis that the presence of KRAS exon 2 mutations might be associated with a lack of response to the epidermal growth factor receptor (EGFR)-targeted monoclonal antibodies (mAbs) panitumumab and cetuximab (Fig. 1) [6–15]. Initial analyses from the 408 study comparing panitumumab + best supportive care (BSC) with BSC alone in patients with mCRC receiving predominantly third-line treatment, supported the use of KRAS as a biomarker [13].Fig. 1


Panitumumab in Metastatic Colorectal Cancer: The Importance of Tumour RAS Status.

Peeters M, Karthaus M, Rivera F, Terwey JH, Douillard JY - Drugs (2015)

The cycle of hypothesis generation/testing to refine the target metastatic colorectal cancer population for panitumumab treatment. ASCO American Society of Clinical Oncology, NCCN National Comprehensive Cancer Network, NGS next-generation sequencing, PCR polymerase chain reaction, PRA prospective–retrospective analysis
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4419154&req=5

Fig1: The cycle of hypothesis generation/testing to refine the target metastatic colorectal cancer population for panitumumab treatment. ASCO American Society of Clinical Oncology, NCCN National Comprehensive Cancer Network, NGS next-generation sequencing, PCR polymerase chain reaction, PRA prospective–retrospective analysis
Mentions: Tumour biomarker status is increasingly used to guide treatment decisions in patients with cancer and has been a rapidly developing area of research in metastatic colorectal cancer (mCRC). Improved patient selection through the use of biomarkers is likely to be particularly beneficial in mCRC because of the heterogeneity of response amongst these patients and the costs and toxicities associated with the available targeted therapies [2]. Approximately 27–43 % of mCRC tumours harbour KRAS exon 2 mutations that lead to constitutive activation of downstream signalling pathways [3]. Results of several uncontrolled [4, 5] and phase II [6] studies led to the hypothesis that the presence of KRAS exon 2 mutations might be associated with a lack of response to the epidermal growth factor receptor (EGFR)-targeted monoclonal antibodies (mAbs) panitumumab and cetuximab (Fig. 1) [6–15]. Initial analyses from the 408 study comparing panitumumab + best supportive care (BSC) with BSC alone in patients with mCRC receiving predominantly third-line treatment, supported the use of KRAS as a biomarker [13].Fig. 1

Bottom Line: Continued cycles of hypothesis generation and biomarker testing in retrospective, prospective-retrospective and prospective analyses from studies of the epidermal growth factor (EGFR)-targeted monoclonal antibodies (mAbs), panitumumab and cetuximab, have resulted in improved patient selection in mCRC.Here, we review key clinical data for panitumumab in mCRC across the lines of treatment, assessing in detail the impact of more comprehensive RAS selection on patient outcomes.Panitumumab data across first- to third-line therapy consistently demonstrate that by testing tumour RAS status, it is possible to select patients more likely to benefit from treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium, Marc.Peeters@uza.be.

ABSTRACT
Tumour biomarker status is being used more and more frequently to guide treatment decisions in patients with metastatic colorectal cancer (mCRC). Continued cycles of hypothesis generation and biomarker testing in retrospective, prospective-retrospective and prospective analyses from studies of the epidermal growth factor (EGFR)-targeted monoclonal antibodies (mAbs), panitumumab and cetuximab, have resulted in improved patient selection in mCRC. Initial data suggested EGFR-targeted mAb treatment should be limited to patients with KRAS exon 2 wild-type (WT) tumours, but the availability of tumour samples from large phase III studies permitted evaluation of additional potential biomarkers of activity for these agents. Subsequent analyses further refined the target population to those patients whose tumours were WT for KRAS and NRAS exons 2, 3 and 4 (i.e., those with RAS WT status). Here, we review key clinical data for panitumumab in mCRC across the lines of treatment, assessing in detail the impact of more comprehensive RAS selection on patient outcomes. Panitumumab data across first- to third-line therapy consistently demonstrate that by testing tumour RAS status, it is possible to select patients more likely to benefit from treatment.

Show MeSH
Related in: MedlinePlus