Results of LIBRETTO-531 support selpercatinib as first-line treatment in patients with RET-mutant metastatic medullary thyroid cancer

Presented during Presidential session I ⁽¹⁾ at the 2023 Congress of the European Society for Medical Oncology (ESMO), 20-24 October in Madrid, Spain, results of the multicenter, randomized, open-label phase III LIBRETTO-531 study support the use of selpercatinib—a highly selective and potent RET inhibitor approved for the treatment of advanced or metastatic RET-mutant medullary thyroid cancer (MTC)—as first-line standard of care in this patient population.

Co-led by Jaume Capdevila, Senior Clinical Investigator of the Vall d’Hebron Institute of Oncology’s (VHIO) Upper Gastrointestinal and Endocrine Tumors Group, LIBRETTO-531 is the first study to directly compare the efficacy of selperatinib versus current standard of care with approved multikinase inhibitors (MKI), cabozantinib or vandetanib.

Medullary thyroid cancer accounts for between 5 to 10% of all thyroid cancer cases. Almost all inherited MTC and more than 50% of sporadic cases of advanced disease are driven by mutations in the RET oncogene, promoting tumor growth and facilitating cancer cell spread.

“While less common, medullary thyroid cancers are more aggressive than differentiated thyroid carcinoma, with a higher risk of local disease recurrence and metastasis,” says Jaume Capdevila, Medical Oncologist at the Vall d’Hebron University Hospital (HUVH) and senior author of this present study. “We are evaluating new first-line treatment options in this population based on the genetic profile of disease to provide these patients with tailored treatment options with an improved safety profile.”

In total, 291 patients with kinase inhibitor-naïve progressive disease were randomized, and the primary endpoint of this study was progression-free survival (PFS). Results, which published in parallel in The New England Journal of Medicine ⁽²⁾, show that the study met the interim analysis criterion of efficacy.

“First-line selpercatinib showed significantly prolonged progression-free survival, improved overall response rate and better overall survival compared with control, demonstrating a 78% reduction in the risk of disease progression,” adds Capdevila.

At a median follow-up of 12 months, median PFS was not reached with selpercatinib. Median PFS was 16.8 months in the control arm. Selpercatinib also achieved a greater decrease in tumor volume with an overall response rate of 69.4% versus 38.8% in patients treated with cabozantinib or vandetanib.

“Our findings highlight the importance of precision therapy for advanced medullary thyroid cancer as well as the molecular characterization of disease prior to treatment. Results also support selpercatinib as first-line standard of care for patients with advanced RET-altered MTC,” concludes Jaume Capdevila, President of the Spanish Neuroendocrine and Endocrine Tumors Group (GETNE).

Abstract reference:

LBA3 – Julien Hadoux , Rossella Elisei, Marcia S. Brose , Ana O. Hoff , Bruce G. Robinson , Ming Gao Barbara Jarzab , Pavel Isaev , Katerina Kopeckova , Jonathan Wadsley , Dagmar Führer , Bhumsuk Keam , Eric J. Sherman , Makoto Tahara , Mimi I. Hu, Yan Lin, Patricia Maeda , Lori J. Wirth , Jaume Capdevila. Randomized Phase 3 Study of Selpercatinib versus Cabozantinib or Vandetanib in Advanced, Kinase Inhibitor-Naïve, RET-mutant Medullary Thyroid Cancer.

Session details:

ESMO Congress 2023

20 – 24 October, Madrid, Spain

Session Type: Presidential 1 – Proffered Paper session

Date: Saturday, 21 October 2023

Time: 16:30 – 18:15

Chairs: Solange Peters (Lausanne, Switzerland), Jean-Yves Blay (Lyon, France)

Room: Madrid Auditorium – Hall 6

Speaker: Julien Hadoux (Villejuif, Cedex, France)

Lecture Time: 17:10 – 17:22

2. Hadoux J, Elisei R, Brose MS, Hoff AO, Robinson BG, Gao M, Jarzab B, Isaev P, Kopeckova K, Wadsley J, Führer D, Keam B, Bardet S, Sherman EJ, Tahara M, Hu MI, Singh R, Lin Y, Soldatenkova VV, Wright J, Lin B, Maeda P, Capdevila J, Wirth LJ. Phase 3 trial of Selpercatinib in RET-mutant MKI-naïve advanced Medullary Thyroid Cancer. N Eng J Med. October 21, 2023 DOI: 10.1056/NEJMoa2309719