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Gene | RET |
Variant | rearrange |
Impact List | unknown |
Protein Effect | unknown |
Gene Variant Descriptions | RET rearrangement indicates an unspecified rearrangement of the RET gene. |
Associated Drug Resistance | |
Category Variants Paths |
RET mutant RET rearrange |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
RET rearrange | lung non-small cell carcinoma | predicted - sensitive | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, Alecensa (alectinib) treatment resulted in objective radiographic response in 50% (2/4) and stable disease in 25% (1/4) of non-small cell lung carcinoma patients harboring RET rearrangement (PMID: 27544060). | 27544060 |
RET rearrange | lung non-small cell carcinoma | predicted - sensitive | Alectinib | Case Reports/Case Series | Actionable | In a retrospective analysis, Alecensa (alectinib) treatment resulted an intracranial response in 1 of 2 patients with RET-rearranged non-small cell lung cancer (PMID: 30017832). | 30017832 |
RET rearrange | lung non-small cell carcinoma | no benefit | Ponatinib | Case Reports/Case Series | Actionable | In a retrospective analysis, multikinase inhibitor treatment demonstrated suboptimal clinical efficacy in RET-rearranged non-small cell lung cancer patients with measurable baseline brain metastasis, with a confirmed intracranial response rate of 18% (2/11); Iclusig (ponatinib) treatment resulted in no intracranial response in 4 patients with evaluable brain metastasis (PMID: 30017832). | 30017832 |
RET rearrange | papillary thyroid carcinoma | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, Iclusig (ponatinib) decreased proliferation of papillary thyroid carcinoma cells harboring the RET/PTC1 rearrangement in culture (PMID: 23526464). | 23526464 |
RET rearrange | papillary thyroid carcinoma | sensitive | Sorafenib | Preclinical | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited RET phosphorylation and activation of downstream signaling, and decreased growth of papillary thyroid carcinoma cells harboring the RET/PTC1 oncogene in culture (PMID: 17664273). | 17664273 |
RET rearrange | lung non-small cell carcinoma | predicted - sensitive | Sunitinib | Clinical Study | Actionable | In a clinical study, analysis of patients with RET-rearranged non-small cell lung cancer treated with RET inhibitors demonstrated a response rate of 18% (2/9, all partial responses), and stable disease in 33% (3/9) of patients following Sutent (sunitinib) treatment (PMID: 28447912). | 28447912 |
RET rearrange | lung adenocarcinoma | no benefit | Sunitinib | Clinical Study - Cohort | Actionable | In a Phase II trial, Sutent (sunitinib) treatment demonstrated limited clinical efficacy, with no objective responses and stable disease in 71% (5/7) of lung adenocarcinoma patients harboring RET rearrangements (PMID: 32312893; NCT01829217). | 32312893 |
RET rearrange | lung non-small cell carcinoma | sensitive | Vandetanib | Clinical Study | Actionable | In a clinical study, analysis of patients with RET-rearranged non-small cell lung cancer treated with RET inhibitors demonstrated a response rate of 18% (2/11, all partial responses) and stable disease in 27% (3/11) of patients following Caprelsa (vandetanib) treatment (PMID: 28447912). | 28447912 |
RET rearrange | lung non-small cell carcinoma | sensitive | Vandetanib | Phase II | Actionable | In a Phase II trial, treatment with Caprelsa (vandetanib) resulted in an objective response rate of 18% (3/17, all partial responses) and disease control rate of 65% (stable disease in 47% (8/17) + partial response in 18% (3/17)) and median progression-free survival of 4.5 months in patients with RET-rearranged metastatic or recurrent non-small cell lung cancer (PMID: 27803005; NCT01823068). | 27803005 |
RET rearrange | lung non-small cell carcinoma | sensitive | Cabozantinib | Guideline | Actionable | Cometriq (cabozantinib) is in guidelines as a first-line and subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring RET rearrangements (NCCN.org). | detail... |
RET rearrange | lung non-small cell carcinoma | sensitive | Cabozantinib | Clinical Study | Actionable | In a clinical study, analysis of patients with RET-rearranged non-small cell lung cancer treated with RET inhibitors demonstrated a response rate of 37% (7/19), with complete response in 5% (1/19) and partial response in 32% (6/19) of patients, and stable disease in 26% (5/19) of patients following Cometriq (cabozantinib) treatment (PMID: 28447912). | 28447912 |
RET rearrange | lung adenocarcinoma | predicted - sensitive | Cabozantinib | Phase II | Actionable | In a Phase II trial, treatment with Cometriq (cabozantinib) resulted in an overall response rate of 28% (7/25) in patients with RET-rearranged lung adenocarcinoma, with a median duration of response of 7.0 months (PMID: 27825636; NCT01639508). | 27825636 |
RET rearrange | lung non-small cell carcinoma | predicted - sensitive | RXDX-105 | Case Reports/Case Series | Actionable | In a clinical case study, a patient with non-small cell lung cancer harboring a RET rearrangement demonstrated a sustained partial response following treatment with RXDX-105 (CEP-32496) on a Phase Ib clinical trial (PMID: 28011461; NCT01877811). | 28011461 |
RET rearrange | lung non-small cell carcinoma | predicted - sensitive | RXDX-105 | Phase I | Actionable | In a Phase Ib trial, treatment with RXDX-105 (CEP-32496) resulted in an overall response rate of 19% (6/31) and stable disease in 39% (12/31) of patients with treatment-naive non-small cell lung cancer harboring a RET fusion (PMID: 30487236; NCT01877811) | 30487236 |
RET rearrange | Advanced Solid Tumor | sensitive | RXDX-105 | Preclinical - Pdx | Actionable | In a preclinical study, CEP-32496 (RXDX-105) induced tumor regression in patient-derived xenograft models of several advanced solid tumor type with RET rearrangements (2015 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; Abstract A174). | detail... |
RET rearrange | lung non-small cell carcinoma | sensitive | Pralsetinib | Guideline | Actionable | Gavreto (pralsetinib) is included in guidelines as a first-line and subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring RET rearrangements (NCCN.org). | detail... |
RET rearrange | lung non-small cell carcinoma | sensitive | Selpercatinib | Guideline | Actionable | Retevmo (selpercatinib) is in guidelines as a first-line and subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring RET rearrangements (NCCN.org). | detail... |