TY - JOUR
T1 - A Phase II Redifferentiation Trial with Dabrafenib-Trametinib and 131I in Metastatic Radioactive Iodine Refractory BRAF p.V600E-Mutated Differentiated Thyroid Cancer
AU - Leboulleux, Sophie
AU - Do Cao, Christine
AU - Zerdoud, Slimane
AU - Attard, Marie
AU - Bournaud, Claire
AU - Lacroix, Ludovic
AU - Benisvy, Danielle
AU - Taïeb, David
AU - Bardet, Stéphane
AU - Terroir-Cassou-Mounat, Marie
AU - Anizan, Nadège
AU - Bouvier-Morel, Emilie
AU - Lamartina, Livia
AU - Lion, Georges
AU - Betrian, Sarah
AU - Sajous, Christophe
AU - Schiazza, Aurélie
AU - Garcia, Marie Eve
AU - Ciappuccini, Renaud
AU - Schlumberger, Martin
AU - Al Ghuzlan, Abir
AU - Godbert, Yann
AU - Borget, Isabelle
N1 - Publisher Copyright:
©2023 American Association for Cancer Research.
PY - 2023/7/5
Y1 - 2023/7/5
N2 - PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
AB - PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
UR - http://www.scopus.com/inward/record.url?scp=85164243973&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-23-0046
DO - 10.1158/1078-0432.CCR-23-0046
M3 - Article
C2 - 37074727
AN - SCOPUS:85164243973
SN - 1078-0432
VL - 29
SP - 2401
EP - 2409
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 13
ER -