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Profile Name RET D898_E901del
Gene Variant Detail

RET D898_E901del (gain of function)

Relevant Treatment Approaches RET Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET D898_E901del Advanced Solid Tumor sensitive RET Inhibitor Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited Erk phosphorylation and growth of transformed cells expressing RET D898_E901del in culture (PMID: 32284345). 32284345
RET D898_E901del Advanced Solid Tumor sensitive RET Inhibitor Pralsetinib Preclinical - Cell culture Actionable In a preclinical study, Gavreto (pralsetinib) inhibited Erk phosphorylation and growth of transformed cells expressing RET D898_E901del in culture (PMID: 32284345). 32284345
RET D898_E901del medullary thyroid carcinoma predicted - resistant RET Inhibitor Vandetanib Case Reports/Case Series Actionable In a clinical case study, a patient with metastatic medullary thyroid carcinoma harboring RET D898_E901del demonstrated primary resistance to Caprelsa (vandetanib) treatment (PMID: 37535881). 37535881
RET D898_E901del medullary thyroid carcinoma sensitive RET Inhibitor Selpercatinib Case Reports/Case Series Actionable In a clinical case study, Retevmo (selpercatinib) treatment resulted in a 61% reduction in the sum of the diameters of the target lesions in a patient with metastatic medullary thyroid carcinoma harboring RET D898_E901del, with treatment lasting 1 year (PMID: 37535881). 37535881
RET D898_E901del Advanced Solid Tumor sensitive RET Inhibitor Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited Ret phosphorylation and proliferation in a transformed cell line expressing RET D898_E901del in culture (PMID: 37535881). 37535881
RET D898_E901del Advanced Solid Tumor resistant RET Inhibitor Cabozantinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing RET D898_E901del were resistant to Cometriq (Cabometyx, cabozantinib) in culture (PMID: 37535881). 37535881
RET D898_E901del Advanced Solid Tumor predicted - sensitive RET Inhibitor Vandetanib Preclinical - Cell culture Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret phosphorylation and proliferation in a transformed cell line expressing RET D898_E901del, but to a lesser degree than cells expressing RET C634R in culture (PMID: 37535881). 37535881
RET D898_E901del medullary thyroid carcinoma sensitive RET Inhibitor Selpercatinib Case Reports/Case Series Actionable In a Phase I/II trial (LIBRETTO-001), Retevmo (selpercatinib) treatment resulted in a clinical response after one month, with a partial response in liver lesions and abdominal lymph nodes that was maintained for 24 months, in a patient with metastatic medullary thyroid carcinoma harboring RET D898_E901del (PMID: 38438731; NCT03157128). 38438731
RET D898_E901del medullary thyroid carcinoma sensitive RET Inhibitor Selpercatinib FDA approved - On Companion Diagnostic Actionable In a Phase I/II trial (LIBRETTO-001) that supported FDA approval, Retevmo (selpercatinib) treatment resulted in an objective response rate (ORR) of 69% (38/55, 5 complete and 33 partial responses) in previously treated adult and pediatric patients of 12 years and older with medullary thyroid cancer harboring RET mutations as detected by an approved test, including RET D898_E901del; ORR was 73% (64/88) in treatment naive patients (PMID: 32846061; NCT03157128). detail... detail... 32846061