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Updated: Jun 9, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Anti-Programmed Death Ligand 1 Plus Targeted Therapy in Anaplastic Thyroid Carcinoma: A Nonrandomized Clinical Trial
Maria E Cabanillas1, Ramona Dadu1, Renata Ferrarotto2
1Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer, Houston.
Importance:
Anaplastic thyroid carcinoma (ATC) is a rare and lethal cancer. Although progress has been made in recent years in patients with mutated BRAF tumors, those who respond initially eventually die of their disease; furthermore, there are no approved therapies for non-BRAF mutated tumors.
Objective:
To determine whether treatment with matched-targeted therapy plus immune checkpoint inhibitors were associated with improved overall survival (OS).
Design, Setting, And Participants:
A phase 2 trial at a single center, tertiary institution with parallel cohorts, assigning treatment with targeted therapy according to the tumor mutation status. Patients with mutated BRAF V600E tumors received vemurafenib/cobimetinib plus atezolizumab (cohort 1); those with mutated RAS (NRAS, KRAS, or HRAS) or NF1/2 tumors received cobimetinib plus atezolizumab (cohort 2). Patients without any of these variants were assigned to receive bevacizumab plus atezolizumab (cohort 3). Patients were enrolled from August 3, 2017, to July 7, 2021. All consecutive, systemic therapy-naive patients with ATC with active disease and who met eligibility criteria were considered for participation. The analysis was conducted in September 2023.
Interventions:
Patients were assigned to targeted therapy based on the driver mutation as follow: BRAF V600E (cohort 1, vemurafenib plus cobimetinib), RAS/NF (cohort 2, cobimetinib), or non-BRAF/RAS/NF (cohort 3, bevacizumab). All received atezolizumab.
Main Outcomes And Measures:
The primary outcome of the study was median OS of the entire targeted therapy cohort, compared with historical median OS of 5 months.
Results:
Forty-three patients with ATC were enrolled in the targeted therapy cohorts, of which 42 were included in the primary analysis. The median OS in patients across these 3 cohorts was 19 months (95% CI, 7.79-43.24). Median OS and progression-free survival per cohort were as follows: cohort 1: 43 months (95% CI, 16-not estimable [NE]), 13.9 months (6.6-64.1); cohort 2: 8.7 months (95% CI, 5.1-37.0) and 4.8 months (1.8-14.7); cohort 3 (vascular endothelial growth factor inhibitor group): 6.21 months (4.1-NE) and 1.3 months (1.3-NE), respectively.
Conclusions And Relevance:
In this nonrandomized clinical trial, atezolizumab combined with targeted therapy resulted in a longer median OS than historical landmark, achieving the study's primary end point, with cohort 1 achieving the longest OS.
Trial Registration:
ClinicalTrials.gov Identifier: NCT03181100.
Insights
Anaplastic thyroid carcinoma (ATC) treatment with targeted therapy plus atezolizumab improved overall survival (OS) compared to historical data. BRAF V600E mutated tumors showed the longest OS in this study.
Area of Science:
- Oncology
- Molecular Biology
- Clinical Trials
Background:
- Anaplastic thyroid carcinoma (ATC) is a rare, lethal cancer with limited therapeutic options.
- Current treatments offer poor prognosis, especially for non-BRAF mutated tumors.
- Targeted therapies show promise but require combination strategies for optimal outcomes.
Purpose of the Study:
- To evaluate the efficacy of matched-targeted therapy combined with immune checkpoint inhibitors in patients with ATC.
- To determine if this combination improves overall survival (OS) compared to historical controls.
Main Methods:
- A phase 2, single-center trial enrolled 43 systemic therapy-naive ATC patients.
- Patients received atezolizumab plus targeted therapy based on tumor mutation status: BRAF V600E (cohort 1), RAS/NF1/2 (cohort 2), or non-BRAF/RAS/NF1/2 (cohort 3).
- Primary outcome was median OS for the entire cohort, compared to a historical median OS of 5 months.
Main Results:
- The median OS for all 42 analyzed patients was 19 months, significantly exceeding the historical median.
- Cohort 1 (BRAF V600E) demonstrated the longest median OS at 43 months.
- Median OS varied by cohort: 8.7 months (cohort 2) and 6.21 months (cohort 3).
Conclusions:
- Combination of atezolizumab with matched-targeted therapy significantly improved OS in ATC patients.
- The study met its primary endpoint, demonstrating the benefit of this novel therapeutic approach.
- BRAF V600E mutation status correlated with the most favorable survival outcomes.
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