1647MO - BRAF mutated anaplastic thyroid carcinoma: Clinical characteristics and outcome under BRAF inhibitors and chemotherapy in real-life practice, a multicentric retrospective study of the French ENDOCAN TUTHYREF network

Background

Anaplastic thyroid carcinoma (ATC) is a rare type of thyroid cancer with a very poor prognosis. The aim of the study was to analyze clinical and biological characteristics and outcome of ATC patients (pts) with BRAF mutations.

Methods

It is a multicentric retrospective study from the French ENDOCAN-TUTHYREF network. ATC pts diagnosed between 2010 and 2020 were identified in our national database. Overall survival (OS) and progression free survival after 1^st line treatment (1L-PFS) were determined by the Kaplan-Meier method.

Results

Among the whole cohort of 360 ATCs, 212 had a molecular analysis and 53 pts (25%) had a BRAF mutation, including 48 with a BRAF V600E mutation. The median age was 72 years (range:50-96) and 31 pts (78%) had an ECOG performance status of 0/1. One pt (2%) had stage IVa, 14 (28%) had stage IVb and 36 (71%) had stage IVc. The stage distribution was not different compared with BRAF wild type (WT) pts. The median value of neutrophil/lymphocyte ratio, available for 38 mutated BRAF pts was 5.16 versus 3.58 in 94 WT pts (p=0.015). Median OS in the BRAF mutated cohort was 6.88 months (95% CI: 3.60-10.45): versus 11.27 (9.09-14.05) in WT pts (p=0.08), regardless the disease stage. Among the 53 BRAF mutated pts, 21 (40%) received BRAF inhibitors: 17 Dabrafenib + Trametinib (8 as 1^st line and 9 post chemotherapy (CT) with a median OS of 14.21 months (4.66-NA) and a median 1L-PFS of 6.38 months (1.79-NA), 4 were treated with Vemurafenib (1 as 1L and 3 post-CT, median OS: 14.91 months (6.88-NA),18 received only CT (OS: 4.05 months (0.83-8.83) and 1L-PFS: 2.15 (0.66 -4.56)) and 14 without CT (OS: 1.31 (0.56-NA). As regard to treatment sequence, Dabrafenib + Trametinib as first line treatment (n=8) improved PFS (6.38 months (1.79-NA) compared with dabrafenib + trametinib after 1st line (n=9) (3.60 months (0.30-12.17) (p=0.07), without difference in OS [8.10 (3.57-NA) versus 14.21(3.60-NA)] respectively (p=0.89).

Conclusions

These results confirm the clinical benefit of BRAF inhibitors in BRAF mutated ATC in a real-life population. BRAF inhibitors improved OS and represents a meaningful treatment option for this aggressive cancer.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

ENDOCAN TUTHYREF French network.

Funding

Has not received any funding.

Disclosure

C. de la Fouchardiere: Financial Interests, Personal, Advisory Board: Merck, Roche, Lilly, Bayer, Amgen, MSD, Servier, Pierre Fabre Oncologie, Bristol-Myers Squibb, Incyte, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Ipsen, Eisai; Financial Interests, Institutional, Invited Speaker: Pierre Fabre Oncologie, Servier. Y. Godbert: Financial Interests, Personal and Institutional, Invited Speaker: Bayer; Financial Interests, Personal, Advisory Board: AztraZeneca; Financial Interests, Personal and Institutional, Advisory Board: esai; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Ipsen, Genzyme, Roche. F. Illouz: Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Invited Speaker: Bayer. L. Lamartina: Financial Interests, Personal, Advisory Board: Bayer, Eisai, Lilly, Ipsen. E.-. Baudin: Financial Interests, Institutional, Advisory Board, Advisory board and principal investigator: Novartis; Financial Interests, Institutional, Advisory Board: HRA, Hutchinson Pharma; Financial Interests, Personal, Other, Project lead and principal investigator: Ipsen; Financial Interests, Institutional, Other: Pfizer; Financial Interests, Personal, Advisory Board: Novartis - AAA; Financial Interests, Institutional, Research Grant: Novartis, HRA, Pfizer; Non-Financial Interests, Principal Investigator: Enterome; Non-Financial Interests, Advisory Role: Hutchinson Pharma; Non-Financial Interests, Leadership Role: Endocan Network. J. Hadoux: Financial Interests, Personal, Advisory Board: Ipsen, Lilly, PharmaMar; Financial Interests, Institutional, Invited Speaker: AAA, Pfizer. All other authors have declared no conflicts of interest.