In a single-institution phase II study reported in JAMA Oncology, Sehgal et al found evidence of activity of nivolumab plus ipilimumab in patients with aggressive thyroid carcinoma.
Study Details
In the trial, 49 evaluable patients enrolled at Dana-Farber Cancer Institute between October 2017 and May 2019 received nivolumab at 3 mg/kg every 2 weeks and ipilimumab at 1 mg/kg every 6 weeks until disease progression, intolerable adverse events, or a maximum of 2 years. The population consisted of 32 patients with radioiodine-refractory differentiated thyroid carcinoma (DTC), 7 patients in an exploratory cohort with medullary thyroid carcinoma (MTC), and 10 patients in an exploratory cohort with anaplastic thyroid carcinoma (ATC). The primary outcome measure was objective response among patients with radioiodine-refractory DTC.
Key Findings
Objective responses (all partial) were observed in 3 of 32 patients (9.4%, 95% confidence interval [CI] = 2.8%–28.5%) in the radioiodine-refractory DTC group, not meeting the predefined criterion for efficacy. Objective response was observed in 2 of 6 patients (33%) with oncocytic carcinoma and in 1 of 5 (20%) with poorly DTC. Clinical benefit rates were 62.5% in the radioiodine-refractory DTC group (including 83.3% among those with oncocytic carcinoma) and 40% among those with poorly DTC.
In the exploratory ATC group, objective responses (all partial) were observed in 3 of 10 patients (30.0%, 95% CI = 6.7%–65.2%), and the clinical benefit rate was 50%. No objective responses were observed in the exploratory MTC group, and the clinical benefit rate was 28.6%.
Among 19 patients with radioiodine-refractory DTC and 9 with ATC with whole-exome sequencing data, the presence of NRAS variants—but not BRAF V600E variants—was associated with significantly poorer progression-free survival (hazard ratio [HR] = 4.8, 95% CI = 1.6–14.3) and overall survival (HR = 7.9, 95% CI = 1.8–35.7). No patients with NRAS variants had an objective response.
Among all patients, treatment-related grade 3 and 4 adverse events occurred in 28.5% and 8.2% of patients; the most common grade 3 event was increased lipase (12%), and the most common grade 4 event was increased lipase (6%). No treatment-related deaths were observed.
The investigators concluded: “This phase II nonrandomized clinical trial reported clinical activity of dual immune checkpoint inhibition in aggressive thyroid cancer. The study did not meet its endpoint in the primary population of radioiodine-refractory DTC and does not support further investigation in non–biomarker-selected DTC. However, the signal observed in ATC may merit further evaluation.”
Kartik Sehgal, MD, of the Department of Medical Oncology, Dana-Farber Cancer Institute, is the corresponding author of the JAMA Oncology article.
Disclosure: The study was funded by Bristol Myers Squibb. For full disclosures of the study authors, visit jamanetwork.com.
