Patient-Reported Tolerability of Selpercatinib Compared to Cabozantinib/Vandetanib: A Secondary Analysis of the LIBRETTO-531 Randomized-Controlled Trial in RET-Mutant Medullary Thyroid Cancer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F25%3A10500736" target="_blank" >RIV/00064203:_____/25:10500736 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/25:10500736

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Vz73YD2vRz" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Vz73YD2vRz</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1177/10507256251367352" target="_blank" >10.1177/10507256251367352</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Patient-Reported Tolerability of Selpercatinib Compared to Cabozantinib/Vandetanib: A Secondary Analysis of the LIBRETTO-531 Randomized-Controlled Trial in RET-Mutant Medullary Thyroid Cancer

Popis výsledku v původním jazyce

Background: Progression-free survival (PFS) may not fully capture the impact of treatment on patients, especially in cancers with longer natural histories and thus, could be complemented by robust measures of patient-reported tolerability (PRT). We report the use of a novel, quantifiable PRT metric as a multiplicity-controlled endpoint to support regulatory and clinical decision-making for selpercatinib use. Comparative PRT was assessed in LIBRETTO-531 (NCT04211337), a randomized phase 3 trial of selpercatinib versus vandetanib/cabozantinib (control) in advanced RET-mutant medullary thyroid cancer (MTC). Patients and Methods: Patients were self-administered the single Functional Assessment of Cancer Therapy item GP5: &quot;I am bothered by side effects&quot; weekly, and scores were dichotomized into &quot;low&quot; (0-2) and &quot;high&quot; (3-4) side-effect burden. PRT measured the proportion of time on treatment (PTT) with &quot;high&quot; side-effect burden for each patient. Comparative PRT was tested at a two-sided significance level of 0.05, conditional on achieving significance for efficacy endpoints. Complementary patient-reported outcomes included health-related quality of life (HRQoL) and symptomatic adverse events self-administered at baseline and at different intervals post-baseline during treatment period. Results: In the tolerability evaluable population (N = 242; selpercatinib n = 161 and control n = 81 [56 received cabozantinib, 25 received vandetanib]), patients on selpercatinib had significantly better PRT with lower PTT with &quot;high side-effect burden&quot; than control (8% vs. 24%, p &lt; 0.0001). Post-baseline compliance rates for PRO questionnaires were generally greater than 80% in both treatment groups. Patients on selpercatinib reported significantly less PTT with HRQoL impairment across physical (36% vs. 52%), role (2% vs. 11%), cognitive (4% vs. 8%), emotional (6% vs. 11%), and social (2% vs. 8%) function (all p &lt; 0.01); and significantly less PTT with severe diarrhea (5% vs. 38%), fatigue (6% vs. 21%), taste change (3% vs. 15%), decreased appetite (2% vs. 15%), and hand-foot syndrome (2% vs. 9%) (all p &lt; 0.001). Conclusion: This study demonstrated superior PRT for selpercatinib compared with control in patients with RET-mutant MTC, further supporting selpercatinib use as the first-line treatment for patients with advanced RET-mutant MTC. Comparative PRT deserves further adoption as a complement to traditional endpoints in future randomized-controlled trials.

Název v anglickém jazyce

Patient-Reported Tolerability of Selpercatinib Compared to Cabozantinib/Vandetanib: A Secondary Analysis of the LIBRETTO-531 Randomized-Controlled Trial in RET-Mutant Medullary Thyroid Cancer

Popis výsledku anglicky

Background: Progression-free survival (PFS) may not fully capture the impact of treatment on patients, especially in cancers with longer natural histories and thus, could be complemented by robust measures of patient-reported tolerability (PRT). We report the use of a novel, quantifiable PRT metric as a multiplicity-controlled endpoint to support regulatory and clinical decision-making for selpercatinib use. Comparative PRT was assessed in LIBRETTO-531 (NCT04211337), a randomized phase 3 trial of selpercatinib versus vandetanib/cabozantinib (control) in advanced RET-mutant medullary thyroid cancer (MTC). Patients and Methods: Patients were self-administered the single Functional Assessment of Cancer Therapy item GP5: &quot;I am bothered by side effects&quot; weekly, and scores were dichotomized into &quot;low&quot; (0-2) and &quot;high&quot; (3-4) side-effect burden. PRT measured the proportion of time on treatment (PTT) with &quot;high&quot; side-effect burden for each patient. Comparative PRT was tested at a two-sided significance level of 0.05, conditional on achieving significance for efficacy endpoints. Complementary patient-reported outcomes included health-related quality of life (HRQoL) and symptomatic adverse events self-administered at baseline and at different intervals post-baseline during treatment period. Results: In the tolerability evaluable population (N = 242; selpercatinib n = 161 and control n = 81 [56 received cabozantinib, 25 received vandetanib]), patients on selpercatinib had significantly better PRT with lower PTT with &quot;high side-effect burden&quot; than control (8% vs. 24%, p &lt; 0.0001). Post-baseline compliance rates for PRO questionnaires were generally greater than 80% in both treatment groups. Patients on selpercatinib reported significantly less PTT with HRQoL impairment across physical (36% vs. 52%), role (2% vs. 11%), cognitive (4% vs. 8%), emotional (6% vs. 11%), and social (2% vs. 8%) function (all p &lt; 0.01); and significantly less PTT with severe diarrhea (5% vs. 38%), fatigue (6% vs. 21%), taste change (3% vs. 15%), decreased appetite (2% vs. 15%), and hand-foot syndrome (2% vs. 9%) (all p &lt; 0.001). Conclusion: This study demonstrated superior PRT for selpercatinib compared with control in patients with RET-mutant MTC, further supporting selpercatinib use as the first-line treatment for patients with advanced RET-mutant MTC. Comparative PRT deserves further adoption as a complement to traditional endpoints in future randomized-controlled trials.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Thyroid

ISSN

1050-7256

e-ISSN

1557-9077

Svazek periodika

35

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

1162-1172

Kód UT WoS článku

001553498200001

EID výsledku v databázi Scopus

2-s2.0-105013645551