Retsevmo ® ▼ (selpercatinib)

This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information.For current prescribing information for all Lilly products, including Summaries of Product Characteristics, Patient Information Leaflets and Instructions for Use, please visit: (England, Scotland, Wales) or (Northern Ireland).

What is the Mechanism of Resistance to Retsevmo® ▼ (selpercatinib) in Some Heavily Pre-treated Patients?

Solvent front rearranged during transfection (RET) G810 mutations, leading to loss of activity, have been identified in heavily pre-treated patients who had disease progression after initial response to selpercatinib.


LIBRETTO-001 Plasma Analysis of Patients Who Progressed

Plasma analyses were performed for patients who had progressed after selpercatinib response.1

Solvent front RET G810 mutations were identified in 2 of 3 patients with medullary thyroid cancer (MTC), and one of 6 patients with NSCLC compared to their detectable ctDNA samples at baseline.1

Pre-Clinical Study

RET G810R mutations were identified in a coiled-coil domain containing 6 (CCDC6)-RET fusion-positive NSCLC patient-derived xenograft acquired resistance to selpercatinib model.1

The model prediction that RET binding could be affected by G810 mutations was confirmed by in vitro experiments that demonstrated loss of activity for an anti-RET multikinase inhibitor (MKI) and selective RET tyrosine kinase inhibitors (TKIs).1

Study Limitations

The authors noted that the actual number of acquired front solvent RET mutations is not represented due to the small number of patients with acquired resistance studied, and that analysis of other biopsy samples will likely uncover additional mechanisms of resistance to selective RET TKIs.1

The LIBRETTO-001 Study

The efficacy of selpercatinib was evaluated in a phase 1/2, multicenter, open-label, single-arm clinical trial in patients with advanced RET fusion-positive NSCLC, RET-mutant MTC, RET fusion-positive thyroid cancer, and RET fusion-positive tumors other than lung or thyroid: Study LIBRETTO-001 (NCT03157128).2-6


1Solomon BJ, Tan L, Lin JJ, et al. RET solvent front mutations mediate acquired resistance to selective RET inhibition in RET-driven malignancies. J Thorac Onc. 2020;15(4):541-549.

2Drilon A, Oxnard GR, Tan DSW, et al. Efficacy of selpercatinib in RET fusion–positive non–small-cell lung cancer. N Engl J Med. 2020;383(9):813-824.

3Wirth LJ, Sherman E, Robinson B, et al. Efficacy of selpercatinib in RET-altered thyroid cancers. N Engl J Med. 2020;383(9):825-835.

4Drilon A, Subbiah V, Gautschi O, et al. Selpercatinib in patients with RET fusion–positive non–small-cell lung cancer: updated safety and efficacy from the registrational LIBRETTO-001 phase I/II trial. J Clin Oncol. 2022. Published online September 19, 2022. https//

5Phase 1/2 study of LOXO-292 in patients with advanced solid tumors, RET fusion-positive solid tumors, and medullary thyroid cancer (LIBRETTO-001). identifier: NCT03157128. Updated August 8, 2022. Accessed September 19, 2022.

6Retsevmo [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Date of Last Review: 21 September 2022

Contact Lilly

Call or Email us

If you want to ask a Medical Information question or you want to report an adverse event or product complaint you can call us or email us at

Available Mon - Fri, 10am - 4pm, excluding Bank Holidays

Or you can

Chat with Us

Click to Chat is Offline

If you have a question, you can chat online with a Lilly Medical Information professional.

Submit a request