A Phase II Redifferentiation Trial with Dabrafenib-Trametinib and 131I in Metastatic Radioactive Iodine Refractory BRAF p.V600E-Mutated Differentiated Thyroid Cancer

• Published in: Clinical cancer research Vol. 29; no. 13; pp. 2401 - 2409
• Main Authors: Leboulleux, Sophie, Do Cao, Christine, Zerdoud, Slimane, Attard, Marie, Bournaud, Claire, Lacroix, Ludovic, Benisvy, Danielle, Taïeb, David, Bardet, Stéphane, Terroir-Cassou-Mounat, Marie, Anizan, Nadège, Bouvier-Morel, Emilie, Lamartina, Livia, Lion, Georges, Betrian, Sarah, Sajous, Christophe, Schiazza, Aurélie, Garcia, Marie-Eve, Ciappuccini, Renaud, Schlumberger, Martin, Al Ghuzlan, Abir, Godbert, Yann, Borget, Isabelle
• Format: Journal Article
• Language: English
• Published: United States 05-07-2023
• Subjects: Adenocarcinoma - etiology; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Humans; Iodine Radioisotopes - adverse effects; Mutation; Oximes - adverse effects; Prospective Studies; Proto-Oncogene Proteins B-raf - genetics; Pyridones - adverse effects; Pyrimidinones; Thyroid Neoplasms - drug therapy; Thyroid Neoplasms - genetics; Thyrotropin Alfa
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-23-0046

To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with a BRAF p.V600E mutation.
A prospective phase II trial including patients with RECIST progression within 18 months and no lesion > 3 cm. Following a baseline recombinant human (rh)TSH-stimulated diagnostic whole-body scan (dc1-WBS), dabrafenib and trametinib were given for 42 days. A second rhTSH-stimulated dc WBS (dc2-WBS) was done at day 28 and 131I (5.5 GBq-150 mCi after rhTSH) was administered at day 35. Primary endpoint was the 6-month RECIST objective response rate. In case of partial response (PR) at 6 or 12 months, a second treatment course could be given. Among 24 enrolled patients, 21 were evaluable at 6 months.
Abnormal 131I uptake was present on 5%, 65%, and 95% of the dc1-WBS, dc2-WBS, and post-therapy scans, respectively. At 6 months, PR was achieved in 38%, stable disease in 52%, and progressive disease (PD) in 10%. Ten patients received a second treatment course: one complete response and 6 PRs were observed at 6 months. The median progression-free survival (PFS) was not reached. The 12- and 24-month PFS were 82% and 68%, respectively. One death due to PD occurred at 24 months. Adverse events (AE) occurred in 96% of the patients, with 10 grade 3-4 AEs in 7 patients.
Dabrafenib-trametinib is effective in BRAF p.V600E-mutated DTC patients for restoring 131I uptake with PR observed 6 months after 131I administration in 38% of the patients.