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

KRAS-Wild Pancreatic Cancer-More Targets than Treatment Possibilities? (PubMed, Cancers (Basel)) - "Currently, selpercatinib, larotrectinib, and repotrectinib are approved by the FDA for the treatment of certain solid tumors harboring specific gene fusions. Recent studies on zenocutuzumab resulted in the FDA-accelerated approval for NGR1 fusion-positive NSCLC and PDAC. Germline mutations may specifically increase responsiveness to poly(ADP-ribose) polymerase (PARP) inhibitors or platinum-based treatments. Comprehensive genomic profiling, incorporating fusion detection and germline testing, is essential to identify patients who may benefit from precision-based approaches."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ALK • FGFR • KRAS • NRG1 • NTRK • RET • ROS1

Advances in Tissue-Agnostic Targeting in Cancer Therapeutics: Current Approvals, Challenges, and Future Directions. (PubMed, Oncol Res) - "The purpose of this review is to explore the impact, safety, and challenges of tissue-agnostic therapies including pembrolizumab, dostarlimab, larotrectinib, entrectinib, repotrectinib, dabrafenib plus trametinib, selpercatinib, and trastuzumab deruxtecan. We discuss emergence of pan-histological biomarkers, such as neoantigen burden, current updates on trials as well as trial outlining strategies to refining patient selection, while also supporting broader access to biomarker testing. Collectively, these insights underscore the transformative role of tissue-agnostic therapies in precision oncology while emphasizing the ongoing need for research to optimize their application and overcome current barriers."

Biomarker • Journal • Pan tumor • Review • Oncology

Understanding the Impact of Cost-Effectiveness Evaluations on Drug Pricing in Japan: A Case Study of Oncology Therapies (ISPOR-EU 2025) - "Eight oncology therapies (Kymriah, Epikinly, Cabometyx, Retevmo, Enhertu, Polivy, Darzquro, Padcev) have completed HTA reports published on the C2H platform. Japan's HTA system actively uses CEA to reassess high-cost oncology drugs. Although several products faced price revisions, the scope and consistency of these impacts vary. Manufacturers must understand the evolving regulatory, reimbursement, and HTA interplay to navigate Japan's market successfully."

Case study • Clinical • Cost effectiveness • HEOR • Pricing

Stress-Induced Structural Divergence of Selpercatinib, a RET Inhibitor: Application of HRMS and NMR for the Discovery of Unique Degradation Products. (PubMed, Biomed Chromatogr) - "One of the degradation products (DP-2) was isolated and characterised through 1D and 2D NMR experiments. The developed method was validated as per ICH Q2 (R2) guidelines and provides valuable information about the stability of SPB, which can offer a strong foundation for its formulation development, quality control and regulatory compliance in bulk drug and dosage forms."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Review and analysis of clinical trials of selective RET inhibitors for the treatment of thyroid cancer. (PubMed, Front Oncol) - "Selpercatinib and pralsetinib are the most frequently studied RET inhibitors. Notably, research on next-generation RET inhibitors as monotherapy approaches (e.g., LOXO-260, enbezotinib, SY-5007 and TY-1091) is currently underway...While selective RET inhibitors have demonstrated therapeutic potential, concerns regarding drug resistance and toxicity persist. Therefore, future strategies should prioritize the development of next-generation inhibitors and the optimization of combination regimens to improve outcomes for RET-altered thyroid cancer patients."

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

Innovent Announces Inclusion of…Drugs…in China's National Reimbursement Drug List (PRNewswire) - "In the updated NRDL, Retsevmo (selpercatinib) is newly listed for the treatment of: 1) adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a RET gene fusion, 2) adult and pediatric patients 12 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation who require systemic therapy, and 3) adult and pediatric patients 12 years of age and older with advanced or metastatic thyroid cancer with a RET gene fusion who require systemic therapy and who are radioactive iodine-refractory."

Reimbursement • Non Small Cell Lung Cancer • Thyroid Gland Medullary Carcinoma

Chylous Ascites, a Rare Adverse Reaction to Selpercatinib. (PubMed, Cureus) - "Reducing the selpercatinib dose and implementing a low long-chain triglyceride diet led to symptom relief, stable ascites, and maintained tumor response. This case highlights effective management of tyrosine kinase inhibitor (TKI)-induced CA without compromising cancer control."

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

Agnostic Biomarkers in Molecular Pathology. (PubMed, J Clin Pract Res) - "The United States Food and Drug Administration (FDA) has approved pembrolizumab for MSI-high tumors or tumors with a high TMB. Larotrectinib and entrectinib have been approved for the treatment of NTRK gene fusion-positive tumors. Additionally, the combination of dabrafenib and trametinib has been approved for BRAF V600E mutations, and selpercatinib has been approved for RET fusion-positive cancers as of 2022. Positive responses to agnostic therapy, a significant milestone in cancer treatment, depend on the identification of new agnostic biomarkers. Ongoing research is focused on defining additional molecular changes, such as programmed death-ligand 1 (PD-L1), Kirsten rat sarcoma virus (KRAS), neuregulin 1 (NRG1), fibroblast growth factor receptor (FGFR), anaplastic lymphoma kinase (ALK), AKT serine/threonine kinase (AKT), human epidermal growth factor receptor 2 (HER2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and breast cancer..."

Biomarker • IO biomarker • Journal • Review • Tumor mutational burden • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Microsatellite Instability • Oncology • Sarcoma • Solid Tumor • ALK • BRAF • BRCA • FGFR • HER-2 • KRAS • MSI • NRG1 • NTRK • PD-L1 • PIK3CA • RET • TMB

Leptomeningeal carcinomatosis as a first sign of metastatic NSCLC: exceptional outcomes with targeted therapy in two illustrative cases (SNO 2025) - "She initiated systemic therapy with carboplatin, pemetrexed, and pembrolizumab, but declined quickly...She is presently continuing therapy on reduced-dose selpercatinib, and is over 2 years from her diagnosis...She is presently continuing therapy on reduced dose trametinib and is over 2 years from her diagnosis. Her MRI of the brain shows no abnormal enhancement."

Clinical • Metastases • Brain Cancer • CNS Disorders • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Solid Tumor • Ventriculomegaly • KRAS

Use of Multilevel Network Meta Regression (ML-NMR) Model in RET Mutation-Positive Medullary Thyroid Cancer (MTC) (ISPOR-EU 2025) - "This case study demonstrates the feasibility of using ML-NMR for comparing time to event outcomes across studies. The findings suggest that selpercatinib is more efficacious than cabozantinib, vandetanib, and placebo for MTC."

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

Selpercatinib plus cemiplimab in RET positive medullary thyroid cancer patient with skin cancers. (PubMed, Tumori) - "The combination of selpercatinib and cemiplimab was possible, with no new safety signals observed."

Journal • Basal Cell Carcinoma • Genetic Disorders • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • RET

RET Receptor Tyrosine Kinase Promotes Breast Cancer Metastasis to the Brain and RET Inhibitors Pralsetinib and Selpercatinib Suppress Breast Cancer Brain Metastases. (PubMed, bioRxiv) - "Using two mouse studies that model multi-organ metastases and breast tumor formation in the brain, we observed that RET inhibition significantly prevented the circulating tumor cells from forming brain metastases and suppressed the growth of intracranially implanted tumor cells, but did not significantly inhibit the progression of well-established brain metastases. Together, our findings demonstrated that RET is highly activated in BCBM and functioning as a novel mediator of BCBM, and that RET plays a new role as a viable therapeutic target for BCBM."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • CTCs • HER-2 • RET

Government to speed new drug coverage in Korea after 46-month delay (Chosun Biz) - "This is part of a public petition calling for the swift inclusion of Eli Lilly and Company’s lung cancer targeted therapy 'Retevmo' in health insurance coverage."

Reimbursement • Non Small Cell Lung Cancer • Thyroid Gland Carcinoma

Preoperative selpercatinib induces major pathological response in a patient with stage IIIA, RET fusion-positive non-small cell lung cancer: A case report. (PubMed, Medicine (Baltimore)) - "This case highlights the potential of selpercatinib in the perioperative setting, suggesting that it induces tumor regression and enabling of curative surgery in early-stage RET fusion-positive NSCLC. Our findings support the further investigation of selpercatinib in early stages and provide a rationale for future treatment strategies of early-stage RET fusion-positive NSCLC patients."

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

PRAC adopted an extension of indication for RETSEVMO to include pediatric patients ≥2 years with advanced RET fusion-positive thyroid cancer, RET-mutant medullary thyroid cancer, and RET fusion-positive solid tumors lacking effective RET-targeted options. The update is supported by final data from the Phase 1/2 LIBRETTO-121 study (J2G-OX-JZJJ). SmPC sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1, 5.2… (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC) Minutes of meeting on 29 Sep - 2 Oct 2025: [AI generated summary]

PRAC • Oncology • Thyroid Gland Carcinoma

Multicenter retrospective study of selpercatinib treatment for advanced or recurrent RET fusion-positive non-small cell lung cancer in Japan. (PubMed, Invest New Drugs) - "In Japanese patients treated with selpercatinib, efficacy in whole patients was similar to the worldwide population, whereas AEs (especially liver dysfunction) was more severe than worldwide population. This result highlights the need for careful dose management strategies for Japanese patients."

Clinical • Journal • Retrospective data • Hepatology • Liver Failure • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • RET

Selpercatinib-induced Acalculous Cholecystitis in an Elderly Patient with RET Fusion-positive Non-small Cell Lung Cancer: A Case Report. (PubMed, Intern Med) - "This is the first reported case of selpercatinib-induced acalculous cholecystitis in a patient. The report highlighted the potential efficacy of selpercatinib in elderly patients while underscoring the risk of severe adverse events and emphasizing monitoring and personalized dose management."

Journal • Gastroenterology • Geriatric Disorders • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KIF5B • RET

A Patient's Journey Toward a Cure: Drugging the Medullary Thyroid Cancer Surfaceome with T Cell Engagers Targeting CEA, GFRA4 and DLL3 as Monotherapy and In Combination with TKIs (SITC 2025) - "In the setting of progressive metastatic MTC, TKIs (selpercatinib, cabozantinib and vandetanib) can prolong survival for some patients, at the expense of side effects and cumulative toxicities.1–3 In particular, daily selpercatinib administration resulted in a robust overall survival (OS) benefit in MTC patients harboring RET mutations.2 However, no randomized trial has demonstrated any OS benefit in RET wild-type patients...Eric Tran (EACRI) and Jena French (UC-Denver) for many thoughtful discussions over the years. They have both gone out of their way to support and inspire."

Clinical • Combination therapy • Monotherapy • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • DLL3 • IFNG • RET

Leptomeningeal carcinomatosis as a first sign of metastatic NSCLC: exceptional outcomes with targeted therapy in two illustrative cases (WFNOS 2025) - "She initiated systemic therapy with carboplatin, pemetrexed, and pembrolizumab, but declined quickly...She is presently continuing therapy on reduced-dose selpercatinib, and is over 2 years from her diagnosis...She is presently continuing therapy on reduced dose trametinib and is over 2 years from her diagnosis. Her MRI of the brain shows no abnormal enhancement."

Clinical • Metastases • Brain Cancer • CNS Disorders • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Solid Tumor • Ventriculomegaly • KRAS

HTA Readiness for Tumor-Agnostic Therapies: Lessons From Analogues Across Major Markets (ISPOR-EU 2025) - "HTA outcomes and payer perceptions were analysed for pembrolizumab, entrectinib, larotrectinib and selpercatinib across 6 key global markets (Australia, Canada, England, France, Germany and Scotland) to determine commonalities and differences in payer reviews and constructive suggestions provided to the manufacturers by the payers. The evidence package for these tumor-agnostic drugs comprised of pooled results from multiple single arm trials. Tumor-agnostic therapies have faced payer scrutiny owing to evidence issues however, there were some signals that payers are willing to engage with manufacturers to provide patient access even without a robust evidence package. It is imperative for the manufacturers and the global market access teams to adopt a tumor-agnostic approach in evidence generation, such as pooled analysis of tumor types."

Pan tumor • Oncology

Selpercatinib Increases Radioactive Iodine Avidity in RET-Fusion Pediatric Thyroid Carcinoma. (PubMed, Pediatrics) - "We describe 2 adolescents with RET-fusion and noniodine avid metastatic PTC who both achieved increased iodine avidity after treatment with selpercatinib, a selective inhibitor of RET, allowing for the successful use of RAI. These cases highlight the potential to include targeted therapy to optimize the treatment with RAI in pediatric patients with noniodine avid advanced PTC."

Journal • Oncology • Pediatrics • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • BRAF • NTRK • RET

Selpercatinib Before Surgery for the Treatment of RET-Altered Thyroid Cancer (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Nov 2025 ➔ Nov 2027 | Trial primary completion date: Nov 2025 ➔ Nov 2027

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Squamous Cell Carcinoma • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • Thyroid Gland Papillary Carcinoma • RET

The Impact of Clinical Evidence on the Inclusion of Non-Small Cell Lung Cancer Drugs in Brazil's Supplementary Healthcare System (ISPOR-EU 2025) - "Favorable recommendations were issued for brigatinib, lorlatinib as first-line treatment, and osimertinib, all supported by Phase 3 trials, with network meta-analyses for brigatinib and lorlatinib. Unfavorable decisions were observed for lorlatinib as a second-line treatment, tepotinib, and selpercatinib, which relied primarily on Phase 2 data, although selpercatinib also included some Phase 3 evidence... Regulatory decisions by ANS are influenced by the robustness of clinical trial evidence. These findings suggest that submissions relying solely on early-phase studies may face greater barriers to approval. This analysis provides valuable insights for optimizing future drug submission strategies within Brazil's supplementary healthcare system."

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

Launch Price Dynamics of Targeted Therapies in NSCLC: Dissecting the Cost and Value Across Biomarker Segments (ISPOR-EU 2025) - "The variation was evident even within mutation types highlighting potential discrepancies in value (e.g., ROS1: $7,760 [taletrectinib] to $9,693 [repotrectinib] to $13,019 [entrectinib]; RET: $11,393 [selpercatinib] to $15,859[pralsetinib]). Despite relatively consistent monthly costs, cost per mPFS month varies significantly within mutation groups. First-line therapies demonstrate superior value, supporting early biomarker testing. Emerging targeted therapies show potential for further improving value propositions through enhanced clinical outcomes."

Biomarker • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • EGFR • KRAS • ROS1

Dual targeting of RET and SRC synergizes in RET fusion-positive cancer cells. (PubMed, Mol Oncol) - "Our results show that the multitargeted SRC TKI dasatinib significantly enhanced the efficacy of RET TKIs in RET fusion-positive (RET+) NSCLC and PTC cells...Importantly, synergy was also observed with eCF506 (NXP900), a next-generation clinical SRC inhibitor. Finally, both SRC TKIs restored sensitivity in selpercatinib-resistant RET+ PTC cells. These results elucidate RET and SRC signaling crosstalk in RET+ NSCLC and PTC, suggesting that co-inhibiting SRC has clinical potential in TKI-naïve and -resistant RET+ cancers."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • RET • RPS6