Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F23%3A10470209" target="_blank" >RIV/00064203:_____/23:10470209 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/23:10470209

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=ZinlAd3CM9" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=ZinlAd3CM9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1056/NEJMoa2309719" target="_blank" >10.1056/NEJMoa2309719</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer

Popis výsledku v původním jazyce

BACKGROUND: Selpercatinib, a highly selective, potent RET inhibitor, has shown efficacy in advanced RET-mutant medullary thyroid cancer in a phase 1-2 trial, but its efficacy as compared with approved multikinase inhibitors is unclear. METHODS: We conducted a phase 3, randomized trial comparing selpercatinib as first-line therapy with the physician&apos;s choice of cabozantinib or vandetanib (control group). Eligible patients had progressive disease documented within 14 months before enrollment. The primary end point in the protocol-specified interim efficacy analysis was progression-free survival, assessed by blinded independent central review. Crossover to selpercatinib was permitted among patients in the control group after disease progression. Treatment failure-free survival, assessed by blinded independent central review, was a secondary, alpha-controlled end point that was to be tested only if progression-free survival was significant. Among the other secondary end points were overall response and safety. RESULTS: A total of 291 patients underwent randomization. At a median follow-up of 12 months, median progression-free survival as assessed by blinded independent central review was not reached in the selpercatinib group and was 16.8 months (95% confidence interval [CI], 12.2 to 25.1) in the control group (hazard ratio for disease progression or death, 0.28; 95% CI, 0.16 to 0.48; P&lt;0.001). Progression-free survival at 12 months was 86.8% (95% CI, 79.8 to 91.6) in the selpercatinib group and 65.7% (95% CI, 51.9 to 76.4) in the control group. Median treatment failure-free survival as assessed by blinded independent central review was not reached in the selpercatinib group and was 13.9 months in the control group (hazard ratio for disease progression, discontinuation due to treatment-related adverse events, or death, 0.25; 95% CI, 0.15 to 0.42; P&lt;0.001). Treatment failure-free survival at 12 months was 86.2% (95% CI, 79.1 to 91.0) in the selpercatinib group and 62.1% (95% CI, 48.9 to 72.8) in the control group. The overall response was 69.4% (95% CI, 62.4 to 75.8) in the selpercatinib group and 38.8% (95% CI, 29.1 to 49.2) in the control group. Adverse events led to a dose reduction in 38.9% of the patients in the selpercatinib group, as compared with 77.3% in the control group, and to treatment discontinuation in 4.7% and 26.8%, respectively. CONCLUSIONS: Selpercatinib treatment resulted in superior progression-free survival and treatment failure-free survival as compared with cabozantinib or vandetanib in patients with RET-mutant medullary thyroid cancer. (Funded by Loxo Oncology, a subsidiary of Eli Lilly; LIBRETTO-531 ClinicalTrials.gov number, NCT04211337.).

Název v anglickém jazyce

Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer

Popis výsledku anglicky

BACKGROUND: Selpercatinib, a highly selective, potent RET inhibitor, has shown efficacy in advanced RET-mutant medullary thyroid cancer in a phase 1-2 trial, but its efficacy as compared with approved multikinase inhibitors is unclear. METHODS: We conducted a phase 3, randomized trial comparing selpercatinib as first-line therapy with the physician&apos;s choice of cabozantinib or vandetanib (control group). Eligible patients had progressive disease documented within 14 months before enrollment. The primary end point in the protocol-specified interim efficacy analysis was progression-free survival, assessed by blinded independent central review. Crossover to selpercatinib was permitted among patients in the control group after disease progression. Treatment failure-free survival, assessed by blinded independent central review, was a secondary, alpha-controlled end point that was to be tested only if progression-free survival was significant. Among the other secondary end points were overall response and safety. RESULTS: A total of 291 patients underwent randomization. At a median follow-up of 12 months, median progression-free survival as assessed by blinded independent central review was not reached in the selpercatinib group and was 16.8 months (95% confidence interval [CI], 12.2 to 25.1) in the control group (hazard ratio for disease progression or death, 0.28; 95% CI, 0.16 to 0.48; P&lt;0.001). Progression-free survival at 12 months was 86.8% (95% CI, 79.8 to 91.6) in the selpercatinib group and 65.7% (95% CI, 51.9 to 76.4) in the control group. Median treatment failure-free survival as assessed by blinded independent central review was not reached in the selpercatinib group and was 13.9 months in the control group (hazard ratio for disease progression, discontinuation due to treatment-related adverse events, or death, 0.25; 95% CI, 0.15 to 0.42; P&lt;0.001). Treatment failure-free survival at 12 months was 86.2% (95% CI, 79.1 to 91.0) in the selpercatinib group and 62.1% (95% CI, 48.9 to 72.8) in the control group. The overall response was 69.4% (95% CI, 62.4 to 75.8) in the selpercatinib group and 38.8% (95% CI, 29.1 to 49.2) in the control group. Adverse events led to a dose reduction in 38.9% of the patients in the selpercatinib group, as compared with 77.3% in the control group, and to treatment discontinuation in 4.7% and 26.8%, respectively. CONCLUSIONS: Selpercatinib treatment resulted in superior progression-free survival and treatment failure-free survival as compared with cabozantinib or vandetanib in patients with RET-mutant medullary thyroid cancer. (Funded by Loxo Oncology, a subsidiary of Eli Lilly; LIBRETTO-531 ClinicalTrials.gov number, NCT04211337.).

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

The New England Journal of Medicine

ISSN

0028-4793

e-ISSN

1533-4406

Svazek periodika

389

Číslo periodika v rámci svazku

20

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

1851-1861

Kód UT WoS článku

001089232200001

EID výsledku v databázi Scopus

2-s2.0-85175638235