Retevmo is the first precision oncology treatment approved specifically for patients with certain RET-driven cancers1,2
Selpercatinib (Retevmo) is a National Comprehensive Cancer Network® (NCCN®)-recommended treatment option for certain patients with RET-positive metastatic non-small cell lung cancer (NSCLC) and RET-positive advanced or metastatic thyroid carcinoma3,4*
*See the NCCN Guidelines for NSCLC for detailed recommendations, including other preferred treatment options.
See NCCN Guidelines® recommendationsNCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
The clinical data for Retevmo were from LIBRETTO-001, a phase I/II, multicohort, open-label, single-arm clinical trial.1,5
Click here to explore clinical trial design.
All results reviewed by an independent review committee (IRC).1,6
Retevmo demonstrated a robust and durable response in certain RET-driven cancers1
In treatment-naive patients with metastatic RET fusion-positive NSCLC (n=39)1:
Median DoR not yet reached (95% CI: 12, NE)1
Median follow-up: 7.4 months1,6
In previously treated† patients with metastatic RET fusion-positive NSCLC (n=105)1:
Median DoR 17.5 months (95% CI: 12, NE)1
Median follow-up: 12.1 months1,6
In systemic therapy-naive‡ patients with advanced or metastatic RET fusion-positive thyroid cancer (non-medullary thyroid cancer (non-MTC))§ (n=8)1:
Median DoR not yet reached (95% CI: NE, NE)1
Median follow-up: 8.8 months1,6
In previously treatedǁ patients with advanced or metastatic RET fusion-positive thyroid cancer (non-MTC) (n=19)1:
Median DoR 18.4 months (95% CI: 7.6, NE)1
Median follow-up: 17.5 months1,6
In cabozantinib/vandetanib treatment-naive patients with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) (n=88)1:
Median DoR 22.0 months (95% CI: NE, NE)1
Median follow-up: 7.8 months1,6
In patients previously treated¶ with cabozantinib and/or vandetanib with advanced or metastatic RET-mutant MTC (n=55)1:
Median DoR not yet reached (95% CI: 19.1, NE)1
Median follow-up: 14.1 months1,6
ORR was defined as CR + PR and was assessed by IRC according to RECIST v1.1.1
Take action on RET. First, test. Then treat.
An FDA-approved test for the detection of RET gene fusions and RET gene mutations is not currently available for Retevmo.1
Select Important Safety Information
The labeling for Retevmo contains Warnings and Precautions for hepatotoxicity, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, tumor lysis syndrome (TLS), risk of impaired wound healing, and embryo-fetal toxicity. Monitor alanine aminotransferase (ALT) and aspartate aminotransferase (AST) prior to initiating Retevmo, every 2 weeks during the first 3 months of treatment, then monthly thereafter and as clinically indicated. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly, and as clinically indicated. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage. If hypersensitivity occurs, withhold Retevmo and begin corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). See full Prescribing Information for further management instructions and dosage modifications for adverse reactions. Closely monitor patients that may be at risk of TLS (rapidly growing tumors, a high tumor burden, renal dysfunction or hydration) and consider appropriate prophylaxis including hydration. Withhold Retevmo for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. Based on data from animal reproduction studies and its mechanism of action, Retevmo can cause fetal harm when administered to a pregnant woman. Advise females and males with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for at least 1 week after the final dose. Serious adverse reactions occurred in 33% of patients who received Retevmo. The most frequent serious adverse reaction (≥2%) was pneumonia. Fatal adverse reactions occurred in 3% of patients; fatal adverse reactions which occurred in >1 patient included sepsis (n=3), cardiac arrest (n=3) and respiratory failure (n=3). Most common adverse reactions, including laboratory abnormalities, (≥25%) were increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), increased glucose, decreased leukocytes, decreased albumin, decreased calcium, dry mouth, diarrhea, increased creatinine, increased alkaline phosphatase, hypertension, fatigue, edema, decreased platelets, increased total cholesterol, rash, decreased sodium, and constipation.
LIBRETTO-001 Trial Design
The phase I/II, multicohort, open-label, single-arm, multicenter LIBRETTO-001 trial evaluated the efficacy of Retevmo in a population of 702 patients with metastatic RET fusion-positive NSCLC (n=332),# advanced or metastatic RET fusion-positive thyroid cancer (non-MTC)** (n=38), advanced or metastatic RET-mutant MTC (n=306), and certain other advanced solid tumors with RET alterations (n=26).†† The study enrolled the following cohorts: systemic therapy-naive patients (n=39‡‡) and previously treated (n=105†‡‡) patients who had progressed on platinum-based chemotherapy with metastatic RET fusion-positive NSCLC; systemic therapy-naive (n=8‡ ‡‡) and previously treated (n=19‖‡‡) patients with advanced or metastatic RET fusion-positive thyroid cancer (non-MTC), and treatment-naive (n=88‡‡) and previously treated (n=55¶‡‡) patients with advanced or metastatic RET-mutant MTC. Major efficacy outcomes were ORR and DoR. In phase II, the dose for Retevmo was 160 mg PO BID.1,5,7§§
†Efficacy was evaluated in 105 adult patients with metastatic RET fusion-positive NSCLC who were previously treated with platinum chemotherapy enrolled into a cohort of LIBRETTO-001. All 105 patients received systemic therapy (with a median of 3 prior systemic regimens). 58 of the 105 patients received prior anti-PD-1/PD-L1 therapy, and 50 of the 105 patients received a prior multikinase inhibitor (MKI).1,7
‡Patients in this cohort received no prior systemic therapy other than radioactive iodine (RAI).1
§Primary tumor histologies included papillary thyroid cancer, poorly differentiated thyroid cancer, anaplastic thyroid cancer, and Hurthle cell thyroid cancer.1
‖Patients in this cohort received a prior systemic therapy (including sorafenib, lenvatinib, or both) other than RAI.1
¶The efficacy of Retevmo was evaluated in 55 patients with RET-mutant advanced MTC who were previously treated with cabozantinib or vandetanib enrolled into a cohort of LIBRETTO-001.1
#Patients with advanced or metastatic RET fusion-positive NSCLC who had progressed on platinum-based chemotherapy and those without prior systemic therapy were enrolled in separate cohorts.1
**Non-MTC by histology included papillary (n=31), poorly differentiated (n=4), anaplastic (n=2), and Hurthle cell (n=1).1,7
††Other tumors included pancreatic cancer (n=7), colon cancer (n=5), and adrenal gland carcinoma (n=3).7
‡‡Number of patients included in the initial efficacy analysis. Efficacy was based on patients who had at least 6 months of follow-up.1
§§Patients with RET-mutant NSCLC and RET-mutant thyroid cancer (non-MTC) were not enrolled in the trial since RET is not the driver of tumor growth in these cancers.1,8
BID=twice daily; CI=confidence interval; CR=complete response; DoR=duration of response; NE=not estimable; NSCLC=non-small cell lung cancer; ORR=objective response rate; PO=orally; PR=partial response; RECIST=Response Evaluation Criteria in Solid Tumors; RET=rearranged during transfection.
See full trial resultsReferences: 1. Retevmo (selpercatinib) [package insert]. Indianapolis, IN: Eli Lilly and Company; 2021. 2. Drilon A, Hu ZI, Lai GGY, et al. Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes. Nat Rev Clin Oncol. 2018;15(3):151-167. 3. Referenced with permission from The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V5.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed June 15, 2021. To view the most recent and complete version of the guidelines, go online to https://www.nccn.org. 4. Referenced with permission from The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Thyroid Carcinoma V1.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed April 9, 2021. To view the most recent and complete version of the guidelines, go online to https://www.nccn.org. 5. Phase 1/2 study of LOXO-292 in patients with advanced solid tumors, RET fusion-positive solid tumors, and medullary thyroid cancer (LIBRETTO-001). https://clinicaltrials.gov/ct2/show/NCT03157128. Updated July 2, 2020. Accessed July 16, 2020. 6. Data on File, Lilly USA, LLC, DOF-SE-US-0032. 7. Data on File, Lilly USA, LLC, DOF-SE-US-0033. 8. Mulligan LM. GDNF and the RET receptor in cancer: new insights and therapeutic potential. Front Physiol. 2019;9:1873.