Atezolizumab and Targeted Therapy in Thyroid Cancer

TOPLINE:

Atezolizumab combined with targeted therapy improved median overall survival to 19 months in patients with anaplastic thyroid carcinoma (ATC). The longest survival was observed in the BRAF V600E cohort, with a median overall survival of 43 months.

METHODOLOGY:

• The median overall survival for ATC has historically been 5 months, with previous research having shown limited efficacy of single-agent targeted therapy and immunotherapy.
• A phase 2 trial was conducted at a single-center, tertiary institution with parallel cohorts, enrolling 43 patients with ATC. The study aimed to evaluate the efficacy of combining atezolizumab with targeted therapy based on tumor mutation status. The rationale for the combination strategy was to achieve a faster onset of action and potentially synergize with immunotherapy.
• Patients were assigned to treatment cohorts on the basis of tumor mutation status: BRAF V600E (vemurafenib/cobimetinib plus atezolizumab), RAS/NF (cobimetinib plus atezolizumab), and non-BRAF/RAS/NF (bevacizumab plus atezolizumab).
• The primary outcome was median overall survival, with secondary outcomes including progression-free survival and overall response rate.
• Patients were enrolled from August 3, 2017, to July 7, 2021, and the analysis was conducted in September 2023. Those included in the study.

TAKEAWAY:

• The median overall survival for patients across all cohorts was 19 months, with the BRAF V600E cohort achieving the longest median overall survival of 43 months.
• The progression-free survival for the BRAF V600E cohort was 13.9 months, while the RAS/NF cohort had a median progression-free survival of 4.8 months.
• The overall response rate was 50% in the BRAF V600E cohort and 14% in the RAS/NF cohort.
• The study demonstrated that combining atezolizumab with targeted therapy could lead to improved survival outcomes in ATC.

IN PRACTICE:

“This nonrandomized clinical trial found that mutation-directed targeted therapy in combination with PD-L1 inhibitor immunotherapy is a promising strategy to extend OS in patients with ATC. Further studies in patients with non-BRAF–mutated ATC, using better targeted agents, are needed,” wrote the authors of the study.

SOURCE:

The study was led by Maria E. Cabanillas, MD, University of Texas MD Anderson Cancer Center in Houston. It was published online on October 24 in JAMA Oncology.

LIMITATIONS:

There was no control arm in the study, which is a common challenge in rare tumor research. The inclusion of surgery and radiation could have contributed to improved survival, although patients were initially unresectable. The study’s findings may be influenced by these factors, and future research should consider these limitations.

DISCLOSURES:

The study was supported by Genentech and the Rare Tumors Initiative as part of the Strategic Research Initiative Development program at the University of Texas MD Anderson Cancer Center. Cabanillas disclosed receiving grants from Genentech and Merck and personal fees from Novartis. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.