Retsevmo ® (selperkatinib)

För fullständig produktresumé för Retsevmo se FASS.

Denna information är endast avsedd för sjukvårdspersonal verksam i Sverige och som svar på din fråga. Informationen nedan är på engelska

Kan hemorragiska händelser inträffa med Retsevmo® ▼ (selperkatinib)?

I LIBRETTO-001-studien ansågs ingen av de tre fatala blödningshändelserna vara relaterade till selperkatinib.

Warnings and Precautions

Serious including fatal hemorrhagic events can occur with selpercatinib. Permanently discontinue selpercatinib in patients with severe or life-threatening hemorrhage.1

Dosing Modifications for Hemorrhagic Events

Modification guidelines for hemorrhagic events are provided in Table 1.1

Table 1. Dose Management for Hemorrhagic Events1

Grade

Dose Modification

Grade 1 or 2

  • No dose modification is required.

Grade 3 or 4

  • Hold dose until toxicity resolves .

  • Discontinue selpercatinib for severe or life-threatening hemorrhagic events.

Selpercatinib and Hemorrhagic Events

Clinical Trial Experience

LIBRETTO-001 is a multicenter, open-label, phase 1/2 study of selpercatinib administered orally to patients with RET fusion-positive solid tumors, RET-mutant MTC, and other tumors with RET activation.1-4

Serious including fatal hemorrhagic events can occur with selpercatinib. Grade ≥3 hemorrhagic events occurred in 2% of patients treated with selpercatinib including 3 (0.4%) patients with fatal hemorrhagic events of

  • cerebral hemorrhage (1)

  • tracheostomy site hemorrhage (1), and

  • hemoptysis (1).1

Overall, 17% of the LIBRETTO-001 population experienced a grade ≤4 hemorrhagic event with 2% of the events being grades 3/4. Of the grades 3/4 events, there was one grade 4 event of hematemesis.1,5

Forty-one preferred terms were included in the hemorrhage analysis. The grade 1/2 events (%) that occurred in ≥1% of the population were  

  • epistaxis (5)

  • hematuria (3)

  • contusion (2)

  • hemoptysis (2)

  • rectal hemorrhage (1), and

  • vaginal hemorrhage (1).5

Of the grade 1/2 events (%) that occurred in ≥1% of the population, those considered related to selpercatinib were

  • epistaxis (8)

  • contusion (2)

  • hematuria (3), and

  • vaginal hemorrhage.5

Grade ≥3 hemorrhagic events occurred in 2% of patients treated with selpercatinib including 3 (0.4%) patients with fatal hemorrhagic events, as seen in Table 2.1,5

Table 2. Grade ≥3 Hemorrhagic Events in the LIBRETTO-001 (N=746)5

 

Severity by Gradea

Event, n (%)b

Grade 3

Grade 4

Grade 5

Gastric hemorrhage

1 (0.1)

NA

NA

Abdominal wall hemorrhage

1 (0.1)

NA

NA

Anal hemorrhage

1 (0.1)

NA

NA

Contusion

1 (0.1)

NA

NA

Cerebral hemorrhage

1 (0.1)

NA

1 (0.1)

Diverticulum intestinal hemorrhagic

1 (0.1)

NA

NA

GI hemorrhage

1 (0.1)

NA

NA

Hematemesis

N/A

1 (0.1)

NA

Hemorrhage intracranial

1 (0.1)

NA

NA

Hemoptysis

1 (0.1)

NA

1 (0.1)

Intra-abdominal hemorrhage

1 (0.1)

NA

NA

Pelvic hematoma

1 (0.1)

NA

NA

Postprocedural hemorrhage

N/A

NA

1 (0.1)

Retroperitoneal hematoma

1 (0.1)

NA

NA

Subdural hemorrhage

1 (0.1)

NA

NA

Traumatic hematoma

1 (0.1)

NA

NA

Upper GI hemorrhage

1 (0.1)

NA

NA

Abbreviations: CTCAE = Common Terminology Criteria for Adverse Events; GI = gastrointestinal; NA = not applicable.

a Severity grade assignment based on CTCAE (v4.03): grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening/debilitating), and grade 5 (fatal).

b Data cut-off March 2020.

Of the grade 3/4 TEAEs that occurred in LIBRETTO-001, hemorrhage intracranial (1 patient) and retroperitoneal hematoma (1 patient) were considered related to selpercatinib.5

Serious Adverse Events

Of the reported hemorrhagic TEAEs, those considered serious and related were hemorrhage intracranial (2 patients) and retroperitoneal hematoma (1 patient).5

Fatal Hemorrhagic Events

The fatal hemorrhagic events reported in LIBRETTO-001 were 

  • cerebral hemorrhage

  • hemoptysis, and

  • postprocedure hemorrhage.1

None of the fatal events were considered to be related to selpercatinib.5

Dosing Modification

Selpercatinib-related dose reductions occurred due to eye hemorrhage (1 patient) and hemorrhage intracranial (1 patient). One patient discontinued selpercatinib due to retroperitoneal hematoma considered related to study drug.5

References

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

2. Phase 1/2 study of LOXO-292 in patients with advanced solid tumors, RET fusion-positive solid tumors, and medullary thyroid cancer (LIBRETTO-001). ClinicalTrials.gov identifier: NCT03157128. Updated July 2, 2020. Accessed January 25, 2020. https://www.clinicaltrials.gov/ct2/show/NCT03157128

3. Wirth 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

4. Drilon 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

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

Glossary

MTC = medullary thyroid cancer

RET = rearranged during transfection

TEAE = treatment-emergent adverse event

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.

Datum fӧr senaste ӧversyn 2021 M01 08


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