Precision Medicine Approach Shows Promise in Anaplastic Thyroid Cancer
核心洞察
Atezolizumab combined with targeted therapies demonstrates improved overall survival in anaplastic thyroid carcinoma (搜索) (ATC) patients with BRAF (搜索) mutations, reaching up to 43 months.
Dual immunotherapy with nivolumab and ipilimumab shows potential in ATC, although it did not meet the prespecified response rate in a mixed cohort of aggressive thyroid cancers.
Biomarker-driven strategies are crucial for enhancing therapies in aggressive thyroid cancers, emphasizing the need for sensitive biomarkers and timely clinical trials.
Two prospective trials have shed light on the potential of immunotherapy and precision medicine in treating thyroid cancer, particularly anaplastic thyroid carcinoma (搜索) (ATC). The studies, published in JAMA Oncology, highlight the importance of biomarker-driven approaches to improve outcomes in this aggressive malignancy.
Atezolizumab Plus Targeted Therapies in BRAF-Mutated ATC
A phase II trial evaluated the combination of atezolizumab (Tecentriq) with mutation-selected targeted agents in patients with unresectable ATC. The study, led by Maria E. Cabanillas, MD, of the University of Texas MD Anderson Cancer Center, included three parallel cohorts based on biomarker status. Patients with BRAF (搜索) V600E-mutated tumors received atezolizumab plus vemurafenib (Zelboraf) and cobimetinib (Cotellic), while those with RAS or NF1/2-mutated tumors received atezolizumab plus cobimetinib. A third cohort without these variants received atezolizumab and bevacizumab (Avastin).
The primary outcome was median overall survival (OS) compared to a historical median of 5 months. The results showed a median OS of 19 months across all evaluable patients. Notably, the BRAF (搜索) V600E-mutated cohort achieved a median OS of 43 months and a progression-free survival (PFS) of 13.9 months.
"The genetically matched targeted therapy plus immunotherapy combination strategy across all cohorts resulted in an OS of 19 months -- to our knowledge the longest OS reported to date in an ATC clinical trial, achieving the primary objective of this study," the authors stated.
These findings compare favorably to the FDA-approved dabrafenib/trametinib (Tafinlar/Mekinist) combination, which showed an ORR of 56%, median PFS of 6.7 months, and median OS of 14.5 months in BRAF (搜索)-mutant ATC. The atezolizumab combination demonstrated a lower ORR but exceeded the survival observed with dabrafenib/trametinib by more than two years.
Dual Immunotherapy with Nivolumab and Ipilimumab
In a separate trial, researchers led by Kartik Sehgal, MD, of Dana-Farber Cancer Institute, investigated dual immunotherapy with nivolumab (Opdivo) and ipilimumab (Yervoy) in a mixed cohort of patients with advanced thyroid cancers, including radioiodine-refractory differentiated thyroid tumors (搜索) (RAIR DTC), ATC, and medullary thyroid cancer (搜索) (MTC).
The primary endpoint was objective response rate (ORR) in the RAIR DTC cohort. While the ORR in this group was 9.4%, exploratory analyses showed partial responses in 30% of patients with ATC. The ATC cohort had a median PFS of 4.3 months, and median OS had not been reached after a median follow-up of 22.2 months.
"The most notable finding of this trial was the potentially promising activity of dual checkpoint inhibition therapy in patients with advanced ATC," Sehgal and co-authors stated.
Expert Commentary
Alfred King-yin Lam, MBBS, MD, PhD, of Griffith University School of Medicine and Dentistry, emphasized the need for sensitive biomarkers to triage and enhance therapies in aggressive thyroid cancers. He noted that combining multiple treatment modalities, including immunotherapy, is expected to improve outcomes for patients with this aggressive cancer.
Implications for Clinical Practice
These studies suggest that precision medicine approaches, incorporating immunotherapy and targeted therapies based on specific genetic mutations, hold promise for improving outcomes in ATC. While dual immunotherapy may offer benefit in some patients, further research is needed to identify predictive biomarkers and optimize treatment strategies.