The link you clicked on will take you to a site maintained by a third party, which is solely responsible for its content. Eli Lilly and Company does not control, influence, or endorse this site, and the opinions, claims or comments expressed on this site should not be attributed to Eli Lilly and Company. Eli Lilly and Company is not responsible for the privacy policy of any third party websites. We encourage you to read the privacy policy of every website you visit.
Tips for searching:
• You have to select a product and type at least 2 words to activate the search
• Use only words that are specific to the information you are looking for
• Avoid typing questions or sentences
Please do not use this field to report adverse events or product complaints. Adverse events and product complaints should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow card in the Google play or Apple app store. Adverse events and product complaints should also be reported to Lilly: please call Lilly UK on 01256 315 000.
This information is intended for UK registered healthcare professionals only in response to your search for information. For current information for all Lilly products, including Summaries of Product Characteristics, Patient Information Leaflets and Instructions for Use, please visit: www.medicines.org.uk
Hypersensitivity is a common, serious side effect of selpercatinib, which requires immediate suspension of selpercatinib and initiation of corticosteroid treatment. Section 4.2 of the summary of product characteristics (SmPC) provides full information on management.1
Section 4.8 of the SmPC provides further details regarding the frequency and the time to onset.1
For complete information, please consult the Retsevmo Summary of Product Characteristics, particularly:
Below is additional data from clinical trials, including information on incidence, severity, management, and mechanism of action of hypersensitivity reactions. A full description of the clinical studies referenced is available in Section 5.1 of the SmPC.1
Incidence of hypersensitivity with selpercatinib
Impact of prior immuno-oncology therapy on hypersensitivity reactions with selpercatinib
Patients with prior immune checkpoint inhibitor treatment in LIBRETTO-001
Anaphylactic reactions in selpercatinib-treated patients
Selpercatinib dosing modifications in clinical studies due to hypersensitivity
Mechanism of action of hypersensitivity reactions
Hypersensitivity is a composite term that includes hypersensitivity and drug hypersensitivity.2
In LIBRETTO-001, drug hypersensitivity was defined as, “a constellation of symptoms and findings characterized by a maculopapular rash, often preceded by fever with associated arthralgias or myalgias, followed by at least one or more of the following signs and symptoms:
Hypersensitivity occurred in 6% of patients receiving selpercatinib in LIBRETTO-001, including grade 3 hypersensitivity in 1.9%. The median time to onset was typically between days 7-21 of therapy.2
LIBRETTO-001 was a single arm phase 1/2 study that included patients with prior treatments as well as those who were treatment naïve.3,4
LIBRETTO-431 was a randomized phase 3 study in patients with treatment naïve NSCLC. The control arm was a regimen of a platinum agent plus pemetrexed with or without pembrolizumab., Patients on the control arm were given the option to crossover to selpercatinib if disease progression had occurred. A total of 36 patients who had received pembrolizumab (approximately 60%) crossed over to receive selpercatinib.5
Across LIBRETTO-001 and LIBRETTO-431, 17% of selpercatinib-treated patients with a history of immune checkpoint inhibitor (ICI) therapy experienced hypersensitivity. Hypersensitivity in Selpercatinib-Treated Patients With a History of Prior Immune Checkpoint Inhibitor Therapy presents an overview of hypersensitivity reactions in patients who received selpercatinib in LIBRETTO-001 or in the intent-to-treat pembrolizumab group.2
Hypersensitivity severity, n (%)a |
LIBRETTO-001b |
|
Overall incidencee |
||
All grades |
26 (15) |
8 (22) |
Grade ≥3 |
7 (4) |
5 (14) |
aHypersensitivity is a composite term that includes hypersensitivity and drug hypersensitivity.
bJune 2023 data cutoff.
cMay 2023 data cutoff.
dThirty-six patients in the intent-to-treat pembrolizumab group crossed over to selpercatinib therapy.
eNo grade 4 or 5 events of hypersensitivity reported.
In LIBRETTO-001, patients pretreated with an ICI may be at increased risk of hypersensitivity reactions with selpercatinib. The overall safety and tolerability in this patient population was not impacted and most patients were able to remain on therapy.3
In LIBRETTO-431, patients randomized to the control group were given the option to crossover to selpercatinib after disease progression. As a result, 42 patients from the control group (approximately 60%) crossed over to receive selpercatinib as their second line of treatment. Eighty percent of the control arm received pembrolizumab.5
Hypersensitivity Reactions in LIBRETTO-431 provides an overview of hypersensitivity reactions and severity in patients who crossed over to selpercatinib in LIBRETTO-431.
Hypersensitivity, n (%) |
Selpercatinib Population |
Selpercatinib Crossover Population |
||
Any Grade |
Grade ≥3 |
Any Grade |
Grade ≥3 |
|
Composite term |
||||
Hypersensitivitya |
3 (2) |
1 (<1) |
8 (19) |
5 (12) |
Preferred terms |
||||
Hypersensitivity |
3 (2) |
1 (<1) |
7 (17) |
4 (10) |
Drug hypersensitivity |
0 |
0 |
1 (2) |
1 (2) |
aComposite term that includes hypersensitivity and drug hypersensitivity.
Two patients in the crossover population (5%) discontinued selpercatinib due to hypersensitivity.2
In a custom safety clustering analysis of the overall safety data as of December 2019 (N=329), hypersensitivity reactions were identified in 30 patients utilizing defined criteria. Twenty-four patients experienced a selpercatinib-related hypersensitivity reaction, with 22 of them being in the NSCLC cohort. Of the 22 patients, 17 had a history of prior ICI therapy. Therapies received by the overall group of patients with prior ICI therapy (N=152) included
Adverse events that occurred in greater than or equal to 20% of patients were comparable in the prior ICI therapy group compared to the overall safety population, with the exception of any grade thrombocytopenia which occurred more in the prior ICI therapy group (24% vs 17%).3
As of the data cutoff date of March 2020, 24.7% (184/746) of patients treated with selpercatinib had previously received anti PD‑1/PD‑L1 immunotherapy. Hypersensitivity occurred in a total of 5.2% (39/746) of patients receiving selpercatinib, including grade 3 hypersensitivity in 1.7% (13/746) of patients.1
Of the 39 patients with hypersensitivity, 64.1% (25/39) had NSCLC and had received prior anti–PD‑1/PD‑L1 immunotherapy.1
Patients in the prior ICI therapy group tended to have more hypersensitivity reactions when compared to patients who did not have prior therapy and to the overall safety population and the NSCLC cohort (Hypersensitivity Reactions by Treatment History Compared to the LIBRETTO-001 Overall Safety Population and NSCLC Cohort).2,3
Prior ICI Therapy |
No Prior ICI Therapy |
|||||
Any grade |
25 (14) |
17 (11) |
14 (3) |
5 (3) |
47 (6) |
34 (10) |
Grade 3 |
7(4) |
5 (3) |
6 (1) |
4 (2) |
15 (2) |
12 (3) |
Serious |
10 (5) |
8 (5) |
4 (1) |
4 (2) |
16 (2) |
14 (4) |
Related to selpercatinib |
||||||
Any grade |
23 (13) |
17 (11) |
8 (1) |
5 (3) |
35 (4) |
30 (9) |
Serious |
10 (5) |
8 (5) |
4 (1) |
4 (2) |
16 (2) |
14 (4) |
Dose modificationh |
||||||
Interruption |
4 (2) |
4 (3) |
2 (<1) |
2 (1) |
32 (4) |
27 (8) |
Reduction |
20 (11) |
14 (9) |
6 (1) |
4 (2) |
31 (4) |
27 (8) |
Discontinuation |
2 (1) |
2 (1) |
1 (<1) |
1 (1) |
3 (<1) |
2 (1) |
Time to first onset |
||||||
Median (range), weeks |
2 (1-16) |
2 (1-3) |
9 (1-77) |
1 (1-5) |
2 (1-112) |
2 (1-22) |
Abbreviations: ICI = immune checkpoint inhibitor; MedDRA = Medical Dictionary for Regulatory Activities; NSCLC = non-small cell lung cancer; TEAE = treatment-emergent adverse event.
aThis analysis is based on consolidated preferred MedDRA terms of “hypersensitivity” and “drug hypersensitivity.”
bPatients with multiple severity ratings for one or more hypersensitivity events were counted once under the maximum severity.
cData cutoff date June 2021.
dData cutoff date December 2019.
eResults are presented regardless of reported causality unless otherwise specified.
fCommon Terminology Criteria for Adverse Events (v4.03).
gA grade 1 or 2 event considered by the investigator to be medically important was reported as a serious event.
hFor each hypersensitivity event resulting in dose modification, a patient was counted once under the most significant action taken (discontinuation, reduction, or interruption, respectively) if more than one action occurred. A patient who experienced multiple events could be counted under more than one action.
In LIBRETTO-001, there were 2 events of grade 1 (n=1) and grade 3 (n=1) anaphylactic reactions reported. The events were not considered serious or related to selpercatinib.2
In LIBRETTO-431, there was one event of grade ≥3 anaphylactic shock reported. It was not considered serious or related to selpercatinib.2
Selpercatinib Dosing Modifications Due to Hypersensitivity provides dose modifications due to hypersensitivity to in selpercatinib-treated patients.
Dosing Adjustment, % |
LIBRETTO-001 |
LIBRETTO-431 |
Interruption |
4 |
<1 |
Reduction |
4 |
1 |
Discontinuation |
<1 |
0 |
aData cut-off January 2023.
bAs of May 2023 data cutoff, LIBRETTO-431 had 158 patients in the selpecatinib group, and 98 patients in the control group.
The exact mechanism of action of these hypersensitivity reactions on selpercatinib are not known, they were deemed to be immune-mediated responses based on the timing of onset and constellation of symptoms and findings.3
Although the initial hypersensitivity events had features similar to a type IV immune-mediated hypersensitivity reaction such as drug reaction with eosinophilia and systemic symptoms (DRESS), they did not fully meet the definition. The hypersensitivity reactions experienced while on selpercatinib treatment had a shorter median time to onset and resolution compared with DRESS, as well as a shorter median time to resolution.3
Additionally, some of the clinical and laboratory manifestation of the reaction from the initial cases were noted to be consistent with cytokine-mediated reactions observed in patients receiving targeted therapies after ICI.3
LIBRETTO-001 is a phase 1/2, multicenter, open-label, single-arm clinical trial (NCT03157128) evaluating efficacy and safety of selpercatinib in patients with advanced rearranged during transfection (RET) fusion-positive solid tumors and RET-mutant medullary thyroid cancer.1,4,6,7
LIBRETTO-431 is a global, open-label, randomized, phase 3 trial comparing selpercatinib to platinum-based chemotherapy and pemetrexed with or without pembrolizumab as initial treatment in patients with locally advanced or metastatic RET fusion-positive nonsquamous NSCLC (NCT04194944).5,8
1Retsevmo [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.
2Data on file, Eli Lilly and Company and/or one of its subsidiaries.
3McCoach CE, Rolfo C, Drilon A, et al. Hypersensitivity reactions to selpercatinib treatment with or without prior immune checkpoint inhibitor therapy in patients with non-small-cell lung cancer in LIBRETTO-001. J Thorac Oncol. 2022;17(6):768-778. https://doi.org/10.1016/j.jtho.2022.02.004
4Drilon 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
5Zhou C, Solomon BJ, Loong K, et al; LIBRETTO-431 Trial Investigators. First-line selpercatinib or chemotherapy and pembrolizumab in RET fusion–positive NSCLC. N Engl J Med. 2023;389(20):1839-1850. https://www.nejm.org/doi/10.1056/NEJMoa2309457
6Wirth 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
7A study of selpercatinib (LOXO-292) in participants with advanced solid tumors, RET fusion-positive solid tumors, and medullary thyroid cancer (LIBRETTO-001). ClinicalTrials.gov identifier: NCT03157128. Updated January 20, 2025. Accessed February 5, 2025. https://www.clinicaltrials.gov/ct2/show/NCT03157128
8Loong HH, Goto K, Solomon BJ, et al. Randomized phase III study of first-line selpercatinib versus pembrolizumab and chemotherapy in RET fusion-positive NSCLC. Abstract presented at: 48th Annual Meeting of the European Society for Medical Oncology (ESMO); October 21 2023; Madrid Spain. Accessed October 21, 2023. https://cslide.ctimeetingtech.com/esmo2023/attendee/confcal/presentation/list?q=Herbert+Loong&r=st~3
Links to references and third-party websites are provided solely for your convenience and to facilitate easy access to the sources cited.
▼ 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: 07 November 2023