Dual Immunotherapy Clinically Active in Anaplastic Thyroid Cancer

Thyroid gland: © Anatomy Insider - stock.adobe.com

Dual immune checkpoint inhibition with nivolumab (Opdivo) and ipilimumab (Yervoy) shows promise for the treatment of anaplastic thyroid cancer (ATC), but offers limited benefit for those with radioiodine refractory differentiated thyroid carcinoma (RAIR DTC), according to findings from a phase 2 study (NCT03246958).¹ 

The study sought to evaluate the efficacy of these immunotherapies in patients with aggressive thyroid cancers. In the trial, 10 patients with ATC experienced a 30% objective response rate (ORR; 95% CI, 6.7%-65.2%), with 50% showing clinical benefit. In the RAIR DTC cohort of 32 patients, 9.4% of patients had an objective response (95% CI, 2.8%-28.5%). In this cohort, all were partial responses in either oncocytic carcinoma (33.0%) or poorly differentiated thyroid carcinoma (20.0%).

The study also showed that no responses were reported in the exploratory medullary thyroid carcinoma (MTC) cohort.

Study Design

The trial was conducted between October 2017 and May 2019, and enrolled 51 patients with aggressive thyroid cancer. This included 32 patients with RAIR DTC, 10 with ATC, and 9 with MTC.

Once enrolled, patients were treated with intravenous nivolumab given at a dose of 3 mg/kg every 2 weeks and ipilimumab at a dose of 1 mg/kg every 6 weeks until disease progression, intolerable adverse events (AEs), or a maximum of 2 years. Data analysis was conducted between June 2021 and September 2023.

The primary end point of the study was the ORR in the RAIR DTC cohort, defined by the RECIST v1.1. Secondary end points included safety, progression-free survival (PFS), overall survival (OS), and biomarker analyses.

Among the 51 patients registered, 49 were evaluable for analysis. The median age was 65 years (range 30-88), and 51% of the patients were female.

Additional Findings

The safety profile of nivolumab and ipilimumab was consistent with previous reports. The most common AEs observed among patients were pruritus, rash, diarrhea, fatigue, and elevation of lipase, and liver enzymes, each of which were generally manageable and aligned with the known safety profile of immune checkpoint inhibitors.

Looking at the biomarker analysis, the presence of NRAS tumor genetic sequence variations was associated with worse outcomes in terms of response to therapy. Further, BRAF V600E mutations did not appear to influence the treatment response in this study.

While the study did not meet its primary end point in the RAIR DTC cohort, further exploration of dual immune checkpoint inhibition in this subtype is warranted.

REFERENCE:

1. Sehgal K, Pappa T, Shin KY, et al. Dual immune checkpoint inhibition in patients with aggressive thyroid carcinoma: A phase 2 nonrandomized clinical trial. JAMA Oncol. Published online October 24, 2024. doi:10.1001/jamaoncol.2024.4019