Immune Checkpoint Inhibitors Show Promising Efficacy in Anaplastic Thyroid Cancer

The use of immune checkpoint inhibitors in anaplastic thyroid cancer shows a similar toxicity profile to that seen in PD-1 and PD-L1 targeting therapies.

Immune checkpoint blockade was well tolerated and had a similar toxicity profile to PD-1/PD-L1-targeting therapies for patients with anaplastic thyroid cancer (ATC), according to findings published in Thyroid.1

Data from a single-center, retrospective case series of patients with histologically confirmed ATC shows that immune checkpoint inhibition may be an effective treatment option with robust sustained responses in this patient population.

“Overall, the median duration of immunotherapy was 1.9 months [range, 1 week-29 months]. The median overall survival was 3.9 months and median progression-free survival was 1.9 months. Among patients with PD-L1 score >50% [n = 8], the median overall survival was 15.5 months. The median overall survival from diagnosis was 15.6 months and remained unchanged regardless of BRAF status,” wrote study authors led by Alycia Hatashima, The Ohio State University and Arthur G. James Cancer Center.

In the study, patients aged 18 years and older with locally advanced or metastatic unresectable ATC were enrolled. All patients were required to have received immune checkpoint inhibitor therapy, consisting of either pembrolizumab (Keytruda) or nivolumab (Opdivo).

Patients received their first dose of their immune checkpoint inhibitor between June 2016 and June 2021. Either a fixed dose of nivolumab at 240 mg or 480 mg given intravenously (IV) every 2 or 4 weeks or pembrolizumab at 200 mg or 400 mg administered IV every 3 or 6 weeks, were administered to those enrolled. All IV infusions were administered over 30 minutes in an outpatient infusion center.

Follow-up imaging assessments were performed at intervals as per the discretion of the treating clinician. Primary and secondary end points of the study were overall survival (OS), progression-free survival (PFS), response rate determined according to RECIST v1.1., and frequency of adverse events as assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 5.0.

Among the 22 patients eligible for inclusion, 13 were enrolled with the median age of 70 years (range, 56-911), 54% (n = 7) were male, 92% were White (n = 12), and 85% (n = 11) had stage IVC disease. Lungs and lymph nodes were the most common sites of metastases in these patients (62% and 46%).

A total of 10 patients (77%) had tumor tissue available for programmed death-ligand 1 (PD-L1) expression testing, and all were positive for PD-L1. Seven of these 10 patients (54%) also had a BRAFV600E mutation.

Of the 13 evaluable patients, 12 received pembrolizumab and 1 patient received nivolumab. There were 10 patients (77%) who had at least 1 prior therapy before receiving an immune checkpoint inhibitor and the median number of prior lines of treatment was 2 (range, 0-5).

Findings showed that the median PFS was 1.9 months and median overall survival (OS) was 3.9 months. The objective response rate was 16% (n = 2). Further, 2 patients had partial response (PR; CI, 0.0-0.4), and 3 patients had durable stable disease (CI, 0.1-0.5).

After a median follow-up of 13.5 months among the patients with a clinical benefit, the median OS had not been reached (range, 4+-29+ months). Responses were ongoing in 4 of the 5 patients.

Regarding safety, the 1-year survival rate was 38% (n = 5) and 6 patients (46%) experienced an immune-related adverse event (AE) while 15% (n = 2) experienced a grade 3 or higher adverse event. This included 1 patient with grade 5 immune checkpoint-related thyroiditis.

All patients (n = 13) experienced at least 1 any grade AE with the most common being, endocrinopathies (23%), rash (15%), nervous system (15%), and musculoskeletal (8%).

In addition to this study, there are several ongoing clinical trials testing pembrolizumab (NCT02688608), nivolumab plus ipilimumab (Yervoy; NCT03246958), and atezolizumab (Tecentriq; NCT03181100), and the combination of anti-PD-1/PD-L1 with targeted therapies in ATC.

Overall, this study shows that immune checkpoint blockade may be an effective and well-tolerated treatment option for patients with ATC.

Reference:
Hatashima A, Archambeau B, Armbruster H, et al. An Evaluation of Clinical Efficacy of Immune Checkpoint Inhibitors for Patients with Anaplastic Thyroid Carcinoma. Thyroid. 2022;32(8):926-936. doi:10.1089/thy.2022.0073