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: www.medicines.org.uk (England, Scotland, Wales) or www.emcmedicines.com/en-GB/northernireland/ (Northern Ireland).

What is the incidence of hypertension using Retsevmo® ▼ (selpercatinib)?

Approximately 28% of the LIBRETTO-001 population experienced selpercatinib-related hypertension. One patient discontinued selpercatinib due to hypertension.

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Incidence of Hypertension in LIBRETTO-001

As of data cut-off June 2021 (N=796), 326 patients (41%) of the LIBRETTO-001 safety population experienced hypertension (Hypertension in the LIBRETTO-001 Trial).1

Overall, 7 patients (1%) experienced a serious adverse event (SAE) of hypertension, including 5 SAEs (1%) which were considered related to study drug.2

The composite term of hypertension included the preferred terms of hypertension, blood pressure increased, and blood pressure abnormal.2

Hypertension in the LIBRETTO-001 Trial1,2

Hypertension severity, n (%)ab

MTC2
(N=319)

NSCLC1
(N=356)

TC2
(N=54)

Safety Population1 (N=796)

Overall incidence

All grades

143 (45)

141 (40)

22 (41)

326 (41)

Grade ≥3

69 (22)

68 (19)

9 (17)

157 (20)

Related to selpercatinib

All grades

102 (32)

95 (27)

15 (28)

224 (28)

Grade ≥3

46 (14)

49 (14)

4 (7)

105 (13)

Abbreviations: MTC = medullary thyroid cancer; NSCLC = non-small cell lung cancer; TC = thyroid cancer.

aData cutoff June 2021.

bThe composite term of hypertension included the preferred terms of hypertension, blood pressure increased, and blood pressure abnormal.

Time to Onset of Hypertension in LIBRETTO-001

As part of a post-hoc safety analysis of LIBRETTO-001 data cutoff 16December2019 (N=702), time to onset of selected treatment-emergent adverse events (TEAEs) was evaluated. Hypertension was analyzed based on a patient's prior medical history before trial enrollment.

The median time for onset for patients with a prior history of hypertension was 2.5 weeks, with a range of 0.1 to 83 weeks. The median time of for onset in patients without a prior history of hypertension was 2.2 weeks, with a range of 0.1 to 60 weeks.3

Dose Modifications Due to Hypertension in LIBRETTO-001 

As of data cut-off June 2021 (N=796), hypertension led to dose interruptions in 6% of patients and dose reductions in 1% of patients. One patient (<1%) discontinued study drug due to hypertension.2

Antihypertensive Therapy Use During LIBRETTO-001

Treatment-emergent hypertension was successfully managed through the addition or adjustment of concomitant antihypertensive medications and selpercatinib dose modifications. Most patients tolerated continued therapy while receiving concomitant antihypertensive therapy such as amlodipine.2

The decision to add antihypertensive medication(s) should be made in accordance with institutional guidelines and incorporating clinical judgment. Eli Lilly and Company does not have any recommendation regarding which antihypertensive medications should be used to treat hypertension while on selpercatinib.

Hypertension Warnings and Precautions for Selpercatinib

Blood pressure should be optimized prior to starting selpercatinib. Do not initiate selpercatinib in patients with uncontrolled hypertension.4

Monitor blood pressure during selpercatinib treatment and treat as needed with standard anti-hypertensive therapy.4

Dosing Modifications for Hypertension With Selpercatinib

Initiate or adjust antihypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue selpercatinib based on the severity (Dose Management for Hypertension).4

Dose Management for Hypertension4

Grade

Dose Modification

1 or 2

No action required.

3

Patient blood pressure should be controlled before starting treatment.

Selpercatinib should be suspended temporarily for medically significant hypertension until controlled with antihypertensive therapy.

Dosing should be resumed at the next lower dose if clinically indicated.

4

Selpercatinib should be discontinued permanently if medically significant hypertension cannot be controlled

Hypertension Mechanism of Action with Selpercatinib

Hypertension is a result of off-target vascular endothelial growth factor (VEGF) inhibition by selpercatinib. The inhibition of VEGF induces vasoconstriction and hypertension.5

Definition of Hypertension in the LIBRETTO-001 Clinical Trial 

The efficacy of selpercatinib was evaluated in a phase 1/2, multicenter, open-label, single-arm clinical trial in patients with advanced rearranged during transfection (RET) fusion-positive non-small cell lung cancer, RET-mutant medullary thyroid cancer, RET fusion-positive thyroid cancer, and RET fusion-positive tumors other than lung or thyroid: Study LIBRETTO-001 (NCT03157128).4,6-8

In the study, adverse events (AEs) were coded using the Medical Dictionary for Regulatory Activities (MedDRA), Version 21 and graded using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03.2

Hypertension was defined as

  • a sustained increase in blood pressure from baseline on ≥2 readings on ≥2 separate occasions, or
  • a clinically significant elevation requiring acute treatment.2

The NCI-CTCAE grade definitions for the AE term “hypertension” are shown in NCI-CTCAE v 4.03 Grade Definitions for Hypertension.

NCI-CTCAE v 4.03 Grade Definitions for Hypertension9

Grade

Definition

1

Prehypertension (SBP 120-139 mmHg or DBP 80-89 mmHg)

2

Stage I HTN (SBP 140-159 mmHg or DBP 90-99 mmHg), medical intervention indicated; recurrent or persistent (≥24 hours), symptomatic increase by >20 mmHg (diastolic) or to >140/90 mmHg if previously WNL, monotherapy indicated

3

Stage 2 HTN (SBP ≥160 mmHg or DBP ≥100 mmHg); medical intervention indicated; more than one drug or more intensive therapy than previously used indicated

4

Life-threatening consequences (eg, malignant HTN, transient or permanent neurologic deficit, hypertensive crisis); urgent intervention indicated

5

Death

Abbreviations: DBP = diastolic blood pressure; HTN = hypertension; NCI-CTCAE = National Cancer Institute-Common Terminology Criteria for Adverse Events; SBP = systolic blood pressure; WNL = within normal limits.

References

1Drilon A, Subbiah V, Gautschi O, et al. Durability of efficacy and safety with selpercatinib in patients with RET fusion+ non-small-cell lung cancer: LIBRETTO-001. Poster presented at European Lung Cancer Congress (ELCC Virtual) 2022; March 30-April 2, 2022.

2Data on file, Eli Lilly and Company and/or one of its subsidiaries.

3Bauer TM, Besse B, Loong HHF, et al. Safety of selpercatinib for RET-altered advanced solid tumors: a post hoc analysis of LIBRETTO-001. Poster presented at: American Association for Cancer Research (AACR/Virtual); April 10-15, 2021. Accessed April 22, 2021. https://assets.ctfassets.net/mpejy6umgthp/2UXgfmZkQecRWJdCbhCpzm/1c617b0391d07ba4a9c37106d8622b75/AACR2021_DV816_Bauer_JZJA.pdf

4Retsevmo [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

5Eskens FA, Verweij J. The clinical toxicity profile of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) targeting angiogenesis inhibitors; a review. European J Cancer. 2006;42(18):3127-39. https://doi.org/10.1016/j.ejca.2006.09.015.

6Drilon 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. https://dx.doi.org/10.1056/NEJMoa2005653

7Wirth LJ, Sherman E, Robinson B, et al. Efficacy of selpercatinib in RET-altered thyroid cancers. N Engl J Med. 2020;383(9):825-835. https://dx.doi.org/10.1056/NEJMoa2005651

8Phase 1/2 study of LOXO-292 in participants with advanced solid tumors, RET fusion-positive solid tumors, and medullary thyroid cancer (LIBRETTO-001). ClinicalTrials.gov identifier: NCT03157128. Updated August 8, 2022. Accessed August 31, 2022. https://www.clinicaltrials.gov/ct2/show/NCT03157128

9US Department of Health and Human Services; National Institutes of Health and National Cancer Institute. Common terminology criteria for adverse events (CTCAE). Version 4.03. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf. Published May 28, 2009. Updated June 14, 2010. Accessed January 30, 2020.

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: 04 April 2022


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