Retevmo (selpercatinib) / Pfizer, Eli Lilly, Innovent Biologics - LARVOL DELTA

A Case of Micro-medullary Thyroid Carcinoma Presenting as Cancer of Unknown Primary. (PubMed, Cureus) - "Given the rapidly progressive disease, vandetanib was initiated while awaiting molecular testing for rearranged during transfection (RET)-alteration. Following the detection of the RET M918T mutation, treatment was switched to selpercatinib, and rapid tumor response and endocrine symptom resolution were observed. This case highlights the importance of evaluating serum calcitonin, specifically in patients with neuroendocrine carcinoma of unknown primary, where MTC should be considered as a critical differential diagnosis. Thyroid ultrasound should be performed to identify even small lesions of medullary thyroid carcinoma (micro-MTC). Identification of MTC not only leads to targeted therapies that may improve prognosis, but also allows for genetic risk assessment and early intervention in family members when multiple endocrine neoplasia type 2 (MEN2) is suspected."

Journal • Cushing’s Disease • Endocrine Cancer • Endocrine Disorders • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • RET

LC-MS/MS method development and validation for novel targeted anticancer therapies adagrasib, capmatinib, ensartinib, entrectinib, larotrectinib, lorlatinib, pralsetinib, selpercatinib and sotorasib. (PubMed, J Pharm Biomed Anal) - "After the validation, 74 plasma samples were measured in the application phase and all results but one fell within the validated ranges. This assay allows simultaneous quantification of nine novel targeted therapies and supports therapeutic drug monitoring."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Targeting RET in medullary thyroid cancer. (PubMed, Endocr Relat Cancer) - "Multikinase inhibitors such as vandetanib and cabozantinib were the first few effective inhibitors which have been shown to slow disease progression in the treatment of advanced MTC. In more recent years, these have been followed by highly-selective RET inhibitors selpercatinib and pralsetinib which have made their way into the clinic, demonstrating high efficacy and a more favourable side-effect profile due to their reduction in off-target effects. In spite of these successes, there remains a continued need to develop strategies to overcome treatment resistance."

Journal • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • RET

Inhibitory Effects of Vandetanib on Catecholamine Synthesis in Rat Pheochromocytoma PC12 Cells. (PubMed, Int J Mol Sci) - "Recently, TKIs, namely, sunitinib and selpercatinib, which were clinically used to target PPGLs, have been reported to decrease catecholamine levels without reducing tumor size. Moreover, both an MEK inhibitor U0126 and a PI3K/AKT inhibitor LY294002 suppressed catecholamine synthesis without decreasing viable cells. This study in rat pheochromocytoma PC12 cells reveals the direct inhibitory effects of vandetanib on catecholamine synthesis via the suppression of RET-ERK and RET-AKT signaling."

Journal • Preclinical • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • RET

RET-fusion metastatic colon cancer responding to selpercatinib-a case report. (PubMed, Oxf Med Case Reports) - "Our patient survived 21 months following initial diagnoses of metastatic recurrence including nine months of selpercatinib. This case underscores the importance of molecular tumor board meetings and the use of next-generation sequencing WES to detect rare and targetable mutations, ultimately improving patient outcomes."

Journal • Tumor mutational burden • Brain Cancer • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • NCOA4 • RET • TMB

Comprehensive genomic profiling to guide personalized targeted and immunotherapy in gastrointestinal tumors: Subgroup analysis of the ROME trial (ESMO-GI 2025) - P2 | "Funding: Erlotinib, Pertuzumab, Vemurafenib, Trastuzumab Emtansine, Alectinib, Vismodegib, Cobimetinib, Atezolizumab, Trastuzumab, Ipatasertib (GDC-0068), Entrectinib and Pralsetinib were provided by Roche; Everolimus, Lapatinib, Alpelisib were provided by Novartis, Palbociclib and Talazoparib were provided by Pfizer, Ipilimumab and Nivolumab were provided by Bristol Myers Squibb (BMS); Brigatinib was provided by Takeda Pharmaceutical Co.; Ponatinib, Itacitinib (INCB039110), Pemigatinib (INCB054828) were provided by Incyte; Selpercatinib was provided by Eli Lilly; Tepotinib was provided by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). CGP with MTB-guided TT may identify patients with GI cancer who benefit from targeted therapies not routinely available in clinical practice. The roles of TMB and potential disease-specific thresholds deserve further investigation."

IO biomarker • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • TMB

Multicenter Retrospective Study of Selpercatinib Treatment for Advanced or Recurrent RET Fusion-Positive NSCLC in Japan (IASLC-WCLC 2025) - "Abstract is embargoed at this time."

Metastases • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • RET

Activation of the AKT-mTOR pathway confers selpercatinib resistance in thyroid cancer cells harboring the CCDC6-RET fusion gene. (PubMed, Biochem Biophys Rep) - "We investigated the growth-inhibitory effects of everolimus, an mTOR inhibitor, and found that TPC-1, TPC-1/SELR, and CUTC48 cells were highly sensitive to the drug. Our results suggest the involvement of AKT-mTOR pathway activation in selpercatinib resistance in thyroid cancer and that inhibition of the AKT-mTOR pathway may have therapeutic potential to overcome selpercatinib resistance."

Journal • Oncology • Solid Tumor • Thyroid Gland Carcinoma • CCDC6 • EGFR • RET

Selpercatinib in Pediatric and Adolescent Patients with RET-Altered Solid Tumors: Safety and Efficacy Results from the Phase 1/2 LIBRETTO-121 Study (ENDO 2025) - P1/2 | "No MTC or PTC pts had PD through data cut off.Conclusions With a median follow-up of 30 months selpercatinib continues to show durable efficacy in pediatric and adolescent pts with RET-altered thyroid cancer and is well tolerated with easily identifiable and manageable toxicities. These results further support the need to identify and target RET alterations with selpercatinib in pediatric and adolescent pts."

Clinical • P1/2 data • Anemia • Cardiovascular • Constipation • Cough • Endocrine Cancer • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hypertension • Oncology • Pain • Pediatrics • Respiratory Diseases • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • Thyroid Gland Papillary Carcinoma • NCOA4 • RET

A Case Report on Pericardial Effusion Associated With Selpercatinib in the First Patient With Rearranged During Transfection (RET) Fusion-Positive Lung Cancer. (PubMed, Cureus) - "Since selpercatinib was approved relatively recently in 2021, the long-term adverse effects of its administration remain unclear. Long-term treatment with selpercatinib may potentially be associated with fluid accumulation, including pericardial effusion, although further studies are needed to clarify this relationship."

Journal • Cardiovascular • Hepatology • Hypertension • Immunology • Liver Failure • Lung Cancer • Oncology • Solid Tumor • RET

Neoadjuvant Treatment With Selpercatinib for RET-Altered Thyroid Cancer: A Multicenter Phase 2 Clinical Trial (ATA 2025) - No abstract available

Clinical • P2 data • Oncology • Solid Tumor • Thyroid Gland Carcinoma

LUNG-MAP Sub-Study: Targeted Treatment for RET Fusion-Positive Advanced Non-Small Cell Lung Cancer (A LUNG-MAP Treatment Trial) (clinicaltrials.gov) - P2 | N=124 | Active, not recruiting | Sponsor: SWOG Cancer Research Network | Trial completion date: Dec 2025 ➔ Mar 2026 | Trial primary completion date: Jun 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • KRAS • MET • RET • ROS1

Selpercatinib in the treatment of thyroid cancer. (PubMed, Future Oncol) - "With approvals from the U.S. FDA and EMA, selpercatinib is recommended as a first-line therapy for advanced RET-mutant MTC and as a second-line option for RAIR DTC. This review explores the molecular underpinnings of thyroid cancer, highlights the therapeutic landscape, and delves into the clinical performance of selpercatinib."

Journal • Review • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • Thyroid Gland Papillary Carcinoma • RET

Sporadic medullary thyroid carcinoma with a rare RET transmembrane domain mutation (A641R) that responds to selpercatinib. (PubMed, Oncologist) - "This case also emphasizes the importance of comprehensive genomic profiling in identifying rare but actionable RET alterations that are undetectable by targeted sequencing companion diagnostic tests. Selpercatinib may represent an effective therapeutic option for patients with medullary thyroid carcinoma driven by uncommon RET mutations, including mutations in the transmembrane domain."

Journal • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • CEACAM5 • RET

Retsevmo: “Extension application to introduce a new pharmaceutical form (film-coated tablets) associated with new strengths (40 mg, 80 mg, 120 mg and 160 mg). The RMP (version 7.1) is updated in accordance” (European Medicines Agency) - CHMP Final Minutes of the meeting on 24 - 27 Feb 2025: “The committee adopted a positive opinion by consensus together with the CHMP assessment report and translation timetable”

CHMP • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma

selpercatinib (Retsevmo) is accepted for restricted use within NHSScotland (Scottish Medicines Consortium) - "Indication under review: as monotherapy for the treatment of adults and adolescents 12 years and older with advanced RET fusion-positive thyroid cancer who are radioactive iodine-refractory (if radioactive iodine is appropriate). SMC restriction: patients who require systemic therapy who have not previously received systemic therapy. In an open-label, single-arm, phase I/II study in adult patients with RET fusion-positive thyroid cancer, 89% of patients who received selpercatinib achieved an objective response."

Reimbursement • Thyroid Gland Carcinoma

“A full HTA is recommended to assess the clinical effectiveness and cost effectiveness of selpercatinib compared with the current standard of care, on the basis of the proposed price relative to currently available therapies” [For rearranged during transfection (RET)-mutant medullary thyroid cancer] (National Centre for Pharmacoeconomics, Ireland)

HEOR • Oncology • Thyroid Gland Medullary Carcinoma

“A full HTA is recommended to assess the clinical effectiveness and cost effectiveness of selpercatinib compared with the current standard of care.” [For advanced RET fusion-positive thyroid cancer who are radioactive iodine-refractory] (National Centre for Pharmacoeconomics, Ireland)

HEOR • Oncology • Thyroid Gland Carcinoma

Overcoming Antibody-Drug Conjugate Resistance in HER2-Positive Breast Cancer: Insights into Molecular Mechanisms and Targeted Therapeutic Approaches (EACR 2025) - "Second-generation antibody-drug conjugates (ADC) trastuzumab deruxtecan (T-DXd; Enhertu®) and trastuzumab duocarmazine (SYD985) have shown effectiveness in HER2-positive and HER2-low metastatic breast cancer...BT-474 and MDA-MB-361 resistant cells retained sensitivity to the ADC trastuzumab emtansine and the tyrosine kinase inhibitors neratinib and lapatinib... Our study provides insight into the molecular basis of ADC resistance, identifying potential targets to overcome resistance and enhance ADC efficacy in HER2-positive breast cancer. The identification of RET downregulation in resistant cells and the observed synergy between T-DXd and selpercatinib highlight a potential strategy for limiting T-DXd resistance."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • IFNG

Dynamic risk stratification-guided management of medullary thyroid carcinoma: integrating surgical precision with RET-targeted therapies and molecular surveillance. (PubMed, Int J Surg) - "Multi-kinase inhibitors (e.g. vandetanib and cabozantinib) have shown increased survival outcomes for metastatic MTCs and are approved as effective treatment options. More recently, selective RET inhibitors like selpercatinib and pralsetinib have demonstrated higher efficacy and better tolerability. Despite these advances, challenges persist in managing MTCs, including addressing biochemical recurrence, determining surgical scope, considering immunotherapy, and treating advanced cases. Personalized medicine approaches, incorporating genetic screening, and innovative therapies, are essential for improving survival and quality of life in MTC patients."

Journal • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • CEACAM5

Patient-Reported Outcomes From LIBRETTO-431: First-Line Selpercatinib Versus Chemotherapy With Pembrolizumab in RET Fusion-Positive NSCLC. (PubMed, JTO Clin Res Rep) - "The selpercatinib group reported better tolerability, as measured by GP5, with a lower proportion bothered by side effects compared with control (22.6% versus 39.7%, OR = 0.58, 95% CI: 0.33-0.99). These PROs, combined with the established efficacy and safety profile of selpercatinib, further support the use of first-line selpercatinib as a standard of care and highlight the importance of early and comprehensive genomic testing in patients with RET fusion-positive NSCLC."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • RET

Case Report: Histological Transformation to Atypical Carcinoid in RET Fusion-positive NSCLC Following Immune Therapy Resistance (PubMed, Zhongguo Fei Ai Za Zhi) - "Subsequent targeted therapy with Selpercatinib after histological transformation demonstrated favorable efficacy, suggesting a potential therapeutic strategy for atypical carcinoid patients with co-occurring rare driver mutations. This case provides a potential therapeutic option for atypical carcinoid patients with rare mutations.."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • RET

An updated patent review of rearranged during transfection (RET) kinase inhibitors (2022-present). (PubMed, Expert Opin Ther Pat) - "While selective RET inhibitors such as selpercatinib have shown clinical success and expanded indications, their use is limited by adverse events and emerging resistance mechanisms. Next-generation RET inhibitors that address these limitations represent a critical frontier in drug development."

Journal • Review • Oncology • RET

Modeling acquired TKI resistance and effective combination therapeutic strategies in murine RET+ lung adenocarcinoma. (PubMed, bioRxiv) - "The tyrosine kinase inhibitors (TKIs) selpercatinib and pralsetinib are approved therapies for RET+ lung cancers and have markedly improved clinical outcomes in these patients, but acquired resistance remains a hurdle to their durable management. By contrast, upfront treatment with selpercatinib and crizotinib in orthotopic tumors yielded complete elimination of 78% of TR.1 tumors and a prolonged duration of response in TR.2 tumors. The findings highlight the failings inherent in treating acquired resistance mechanisms at progression and the potential therapeutic impact of predicting and targeting dominant mechanisms of resistance prior to or early after initiating oncogene-targeting TKI treatment in RTK-driven LUAD."

Journal • Preclinical • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Transplantation • ERBB4 • GAB1 • HER-2 • NRG1 • NRP1 • PTPN11 • RET • TRIM24

Successful surgical management of a patient with osteoradionecrosis of the jaw with RET fusion-positive advanced thyroid cancer: A case report. (PubMed, Exp Ther Med) - "The present case study reported on a patient with advanced PTC who developed ORN during lenvatinib treatment; extensive surgical treatment with submandibular dissection for ORN provided a favorable outcome...CGP identified a CCDC6-RET fusion, prompting selpercatinib treatment, which achieved a partial response...In addition, submandibular dissection is warranted in selected patients, particularly when thyroid cancer exhibits an aggressive phenotype with occult metastases. Furthermore, this report highlights the importance of integrating personalized medicine in the management of advanced cancer cases and emphasizes the availability of genomic profiling to guide treatment decisions."

Journal • Endocrine Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • CCDC6 • RET