Molecular Profile Detail

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Profile Name RET fusion
Gene Variant Detail

RET fusion (unknown)

Relevant Treatment Approaches RET Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET mutant Advanced Solid Tumor sensitive Ponatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Iclusig (ponatinib) inhibited proliferation of cancer cell lines harboring RET mutations in cultured and in cell line xenograft models (PMID: 23526464). 23526464
RET mutant cancer sensitive Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited wild-type RET and RET mutations to prevent cell proliferation in cell culture (PMID: 17664273). 17664273
RET mutant colorectal cancer sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) demonstrated efficacy in RET mutant positive colorectal cancer cell lines (PMID: 23811235). 23811235
RET rearrange thyroid gland papillary 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 thyroid gland papillary 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 mutant thyroid gland medullary carcinoma sensitive Everolimus Phase II Actionable In a Phase II trial, Afinitor (everolimus) treatment resulted in stable disease in 71% (5/7) of medullary thyroid cancer patients, including patients harboring RET mutations, with median progression-free survival of 33 weeks (PMID: 26294908; NCT01118065). 26294908
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 mutant thyroid gland medullary carcinoma sensitive Cabozantinib Phase III Actionable In a Phase III trial, Cometriq (cabozantinib) treatment resulted in improved progression free survival (60 vs 20 weeks) compared to placebo in thyroid medullary carcinoma patients harboring RET mutations (PMID: 27525386). 27525386
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 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 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 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 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 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 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 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 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 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 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 mutant thyroid gland medullary carcinoma sensitive Selpercatinib FDA approved 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), with five complete and 33 partial responses, in adult and pediatric patients of 12 years and older with medullary thyroid cancer harboring RET mutations who were previously treated, while patients who had not been previously treated demonstrated an ORR of 73% (64/88), with ten complete and 54 partial responses (PMID: 32846061; NCT03157128). detail... detail... 32846061
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...
RET mutant pheochromocytoma predicted - sensitive Sunitinib Case Reports/Case Series Actionable In a Phase II trial (SNIPP), a patient with pheochromocytoma harboring a germline RET mutation achieved a partial response to treatment with Sutent (sunitinib), and demonstrated a 64% reduction in tumor volume and remained on treatment for over 7 years (PMID: 31105270). 31105270
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 mutant thyroid gland medullary carcinoma sensitive Pralsetinib FDA approved Actionable In a Phase I/II trial (ARROW) that supported FDA approval, Gavreto (pralsetinib) treatment was well-tolerated and resulted in an overall response rate (ORR) of 60% (3/55) in patients with advanced or metastatic medullary thyroid cancer harboring RET mutations who received prior treatments, ORR was 60% (32/53) in patients with prior therapies and 71% (15/21) in treatment-naive patients (PMID: 34118198; NCT03037385). 34118198 detail...
RET mutant lung non-small cell carcinoma unknown unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective clinical study, patients with non-small cell lung cancer harboring rare targetable drivers (RTD) (BRAF, ERBB2/3, RET, MET, ROS1, NTRK) who received immune checkpoint inhibitors (ICI) achieved longer median overall survival (mOS) (32 vs 13 mo, p=0.01) compared to those who did not receive ICI, mOS was 44.9 mo in a patient harboring RET mutation, although RTD type was not associated with OS in a univariate analysis (PMID: 30268448). 30268448
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 mutant thyroid gland medullary carcinoma sensitive Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines for adult or pediatric patients 12 years or older with advanced or metastatic medullary thyroid gland carcinoma harboring RET mutations (PMID: 31549998, PMID: 35491008; ESMO.org). 31549998 detail... 35491008
RET mutant thyroid gland medullary carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for adult or pediatric patients 12 years or older with advanced medullary thyroid gland carcinoma harboring RET mutations (PMID: 31549998, PMID: 35491008; ESMO.org). 31549998 detail... 35491008
RET mutant thyroid gland medullary carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with medullary thyroid carcinoma harboring RET mutations (NCCN.org). detail...
RET mutant thyroid gland medullary carcinoma sensitive Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines (category 2B) for patients with medullary thyroid carcinoma harboring RET mutations (NCCN.org). detail...
RET mutant Advanced Solid Tumor predicted - sensitive EP0031 Phase Ib/II Actionable In a Phase I/II trial (KL400-I/II-01), EP0031 treatment was well tolerated and demonstrated preliminary activity in patients with advanced solid tumors harboring mutations in RET, resulting in an objective response rate of 64%, with responses being observed in patients with non-small cell lung cancer, medullary thyroid cancer and pancreatic cancer (J Clin Oncol 41, 2023 (suppl 16; abstr 3007); NCT05265091). detail...
RET mutant lung non-small cell carcinoma predicted - sensitive EP0031 Phase Ib/II Actionable In a Phase I/II trial (KL400-I/II-01), EP0031 treatment was well tolerated in non-small cell lung cancer (NSCLC) patients harboring RET mutations, and resulted in an objective response rate (ORR) of 63% (20/32, 1 complete response (CR)) and disease control rate (DCR) of 91% in pretreated patients, and an ORR of 76% (19/25, 1 CR) and DCR of 92% with median duration of response not reached in treatment-naive patients, and an overall CNS DCR of 100% (J Clin Oncol 41, 2023 (suppl 16; abstr 3007); NCT05265091). detail...