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

Vilka var de vanligaste hematologiska biverkningarna med Retsevmo® ▼ (selperkatinib)?

De flesta av de onormala laboratorievärdena och hematologiska biverkningarna var av svårighetsgrad 1 eller 2.

LIBRETTO-001 Clinical Trial

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

Inclusion Criteria

Criteria for trial participation included adequate hematologic status for at least 7 days prior to treatment defined as

  • ANC ≥ 1.0 × 109/L not requiring growth factor support

  • platelet count ≥ 75 × 109/L not requiring transfusion support, and

  • Hgb ≥ 9 g/dL not requiring transfusion support or erythropoietin.5

Patients were not allowed to receive concomitant hematopoietic growth factors for prophylaxis in cycle 1.5

Hematologic Treatment-Emergent Adverse Events

Hematologic TEAEs that occurred in ≥1% of the safety population are presented in Table 1.

Table 1. Hematologic TEAEs by Grade and Relatedness in ≥1% of the LIBRETTO-001 Safety Population (N=746)5 

TEAE, %

Any Grade (Related)

Grade 3/4 (Related)

Thrombocytopenia

14 (10)

3 (2)

Leukopenia

11 (7)

1 (1)

Lymphopenia

11 (5)

4 (1)

Anemia

9 (3)

2 (<1)

Neutropenia

9 (6)

2 (2)

Thrombocytosis

1 (1)

0 (<1 )

Polycythemia

1 (0)

0 (0)

TEAE = treatment-emergent adverse event.

Serious hematologic TEAEs deemed to be related to selpercatinib were thrombocytopenia in 2 patients and lymphopenia in 1 patient.5

Laboratory Abnormalities

Table 2 provides the abnormal chemistry values in LIBRETTO-001. The majority of these events were grade 1 in severity.5

Table 2. Laboratory Abnormalities That Occurred in ≥1% of the Overall LIBRETTO-001 Clinical Trial Population (N=746)5

Chemistry, %

Any Grade

Grades 3-4

Increased AST

33

8

Increased ALT

33

10

Increased creatinine

21

<1

Increased alkaline phosphatase

12

1

Increased bilirubin

10

1

Increased total cholesterol

4

0

Decreased magnesium

1

<1

Increased glucose

1

0

Decreased albumin

1

0

Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase.

Serious selpercatinib-related changes in serum chemistry were increased AST and increased ALT in 9 patients each.5

Dose Modifications

Hematologic TEAEs

Two patients (<1%) permanently discontinued selpercatinib due to thrombocytopenia.5 Events that occurred in ≥1% of the population and led to dose modification in the LIBRETTO-001 clinical trial are presented in Table 3

Table 3. Dose Modifications Due to TEAEs in ≥1% of the LIBRETTO-001 Safety Population (N=746) 5

TEAE, n (%)

Dose Interrupted

Dose Reduced

Thrombocytopenia

9 (1)

11 (2)

Neutropenia

5 (1)

5 (1)

Anemia

4 (1)

N/Aa

Abbreviations: N/A = not applicable; TEAE = treatment-emergent adverse event.

a 1 (<1%) patient had a dose reduction due to anemia.

Abnormal Serum Chemistry Values

Permanent discontinuation of selpercatinib due to abnormal laboratory values occurred in

  • 3 patients due to ALT increased

  • 2 patients due to AST increased, and

  • 1 patient due to blood bilirubin increased.5

Dose modifications due to abnormal laboratory values in ≥1% of the LIBRETTO-001 population are presented in Table 4.

Table 4. Dose Modifications Due to Abnormal Laboratory Values in ≥1% of the LIBRETTO-001 Safety Population (N=746)5

TEAE, n (%)

Dose Interrupted

Dose Reduced

ALT increased

42 (6)

53 (7)

AST increased

37 (5)

48 (6)

Blood creatinine increased

0

7 (1)

Blood bilirubin increased

11 (2)

4 (1)

Alkaline phosphatase increased

6 (1)

4 (1)

Liver function test increased

N/Aa

4 (1)

Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; N/A = not applicable; TEAE = treatment-emergent adverse event.

a 3 patients (<1%) had dose interruptions due to increased liver function test.

References

1. 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

2. 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

3. 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

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

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

Glossary

ALT = alanine aminotransferase 

ANC = absolute neutrophil count

AST = aspartate aminotransferase

Hgb = hemoglobin

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 28


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