Molecular Profile Detail

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Profile Name POLE P286R
Gene Variant Detail

POLE P286R (loss of function)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
POLE P286R colorectal cancer predicted - sensitive Nivolumab Case Reports/Case Series Actionable In a Phase II trial, Opdivo (nivolumab) resulted in a complete response in a colorectal cancer patient harboring POLE P286R, along with high tumor mutational burden and CD8-positive high tumor infiltrating lymphocytes, and a partial response in a different colorectal cancer patient also harboring POLE P286R, along with high tumor mutational burden (PMID: 35398880; NCT03012581). 35398880
POLE P286R endometrial cancer predicted - sensitive Nivolumab Case Reports/Case Series Actionable In a Phase II trial, Opdivo (nivolumab) resulted in stable disease in an endometrial cancer patient harboring POLE P286R, along with high tumor mutational burden (PMID: 35398880; NCT03012581). 35398880
POLE P286R melanoma sensitive unspecified CTLA4 antibody Preclinical Actionable In a preclinical study, a murine anti-CTLA4 antibody inhibited tumor growth and improved survival in a syngeneic mouse model of melanoma expressing POLE P286R (PMID: 35817971). 35817971
POLE P286R melanoma sensitive unspecified PD-1 antibody Preclinical Actionable In a preclinical study, a murine anti-PD1 antibody inhibited tumor growth and improved survival in a syngeneic mouse model of melanoma expressing POLE P286R (PMID: 35817971). 35817971
POLE P286R melanoma sensitive unspecified CTLA4 antibody + unspecified PD-1 antibody Preclinical Actionable In a preclinical study, the combination of a murine anti-CTLA4 antibody and a murine anti-PD1 antibody inhibited tumor growth and improved survival in a syngeneic mouse model of melanoma expressing POLE P286R (PMID: 35817971). 35817971
POLE P286R colorectal cancer sensitive unspecified CTLA4 antibody Preclinical Actionable In a preclinical study, a murine anti-CTLA4 antibody inhibited tumor growth in a syngeneic mouse model of colorectal cancer expressing POLE P286R (PMID: 35817971). 35817971
POLE P286R colorectal cancer sensitive unspecified PD-1 antibody Preclinical Actionable In a preclinical study, a murine anti-PD1 antibody inhibited tumor growth in a syngeneic mouse model of colorectal cancer expressing POLE P286R (PMID: 35817971). 35817971
POLE P286R colorectal cancer sensitive unspecified CTLA4 antibody + unspecified PD-1 antibody Preclinical Actionable In a preclinical study, the combination of a murine anti-CTLA4 antibody and a murine anti-PD1 antibody inhibited tumor growth in a syngeneic mouse model of colorectal cancer expressing POLE P286R (PMID: 35817971). 35817971
POLE P286R colorectal cancer predicted - sensitive Ipilimumab + Nivolumab Case Reports/Case Series Actionable In a retrospective study, treatment with immune checkpoint inhibitors resulted in an overall response rate of 89% (22/29) and a disease control rate of 92% in metastatic colorectal cancer patients harboring pathogenic POLE/POLD1 variants, including a partial response in 4 patients and a complete response in 1 patient, all harboring POLE P286R and treated with Yervoy (ipilimumab) plus Opdivo (nivolumab) (PMID: 38777726). 38777726
POLE P286R colorectal cancer predicted - sensitive Pembrolizumab Case Reports/Case Series Actionable In a retrospective study, treatment with immune checkpoint inhibitors resulted in an overall response rate of 89% (22/29) and a disease control rate of 92% in metastatic colorectal cancer patients harboring pathogenic POLE/POLD1 variants, including a partial response in 2 patients and complete response in 2 patients out of 5 patients harboring POLE P286R and treated with Keytruda (pembrolizumab) (PMID: 38777726). 38777726
POLE P286R colorectal cancer predicted - sensitive Nivolumab Case Reports/Case Series Actionable In a retrospective study, treatment with immune checkpoint inhibitors resulted in an overall response rate of 89% (22/29) and a disease control rate of 92% in metastatic colorectal cancer patients harboring pathogenic POLE/POLD1 variants, including a complete response in a patient harboring POLE P286R treated with Opdivo (nivolumab) (PMID: 38777726). 38777726