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| Gene | RET |
| Variant | fusion |
| Impact List | fusion |
| Protein Effect | unknown |
| Gene Variant Descriptions | RET fusion indicates a fusion of the RET gene, but the fusion partner is unknown. |
| Associated Drug Resistance | |
| Category Variants Paths |
RET mutant RET rearrange RET fusion |
| 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 | 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 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 | 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 | 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 | 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 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 | 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 | 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 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 | 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 | 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 | 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 | 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 mutant | medullary thyroid 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 mutant | medullary thyroid 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 | medullary thyroid 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 | medullary thyroid carcinoma | sensitive | Selpercatinib | FDA approved - Has Companion Diagnostic | Actionable | In a Phase I/II trial (LIBRETTO-121) that supported FDA approval, Retevmo (selpercatinib) treatment was safe in pediatric patients of 2 years or older with solid tumors (8 medullary thyroid cancer, 2 papillary thyroid cancer, 1 osteosarcoma) harboring RET fusion (n=2) or mutations (n=9), and resulted in unconfirmed partial responses in 4 patients, stable disease in 6 patients (two lasting >/=16 weeks) (JCO 39, 10009-10009(2021); NCT03899792). | detail... detail... detail... |
| RET mutant | medullary thyroid carcinoma | sensitive | Selpercatinib | FDA approved - Has 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), 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 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 mutant | medullary thyroid 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 | medullary thyroid carcinoma | sensitive | Pralsetinib | Phase Ib/II | Actionable | In a Phase I/II trial (ARROW), 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 |
| RET mutant | medullary thyroid 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 | medullary thyroid 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 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 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 | 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 | 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 | 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 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... |