In a phase II study reported in the Journal of Clinical Oncology, Jaume Capdevila, MD, and colleagues found that the programmed cell death protein 1 (PD-1) inhibitor spartalizumab produced responses in a cohort of patients with locally advanced or metastatic anaplastic thyroid carcinoma, with all responses being observed in patients with programmed cell death ligand 1 (PD-L1)-positive tumors.

Jaume Capdevila, MD

Study Details

In the international multicenter trial, 42 patients received 400 mg of spartalizumab intravenously once every 4 weeks until disease progression or unacceptable toxicity. Progression on prior therapy was not required. Overall, 59% of patients had received one or more prior treatment regimen(s). Response was assessed by Response Evaluation Criteria in Solid Tumors, version 1.1.  

Responses

Response was observed in eight patients (19%), with complete response observed in three. Median duration of response was not reached, with response durations ranging from 16.7 weeks to 1.6 years (ongoing at data cutoff).

Among 40 patients with known PD-L1 expression status, response was observed in 8 of 28 (29%) PD-L1–positive patients (≥ 1% in tumor cells) vs 0 of 12 (0%) PD-L1–negative patients. Response was observed in 6 (35%) of 17 patients with PD-L1 expression ≥ 50%. Among 38 patients with known BRAF-mutation status, 12 (29%) had BRAF-mutant disease; response rates were 8% vs 23% in those with vs without a BRAF mutation.

Median progression-free survival among all patients was 1.7 months. Progression-free survival at 1 year was 0%, 20%, and 29%, among patients with PD-L1 expression < 1%, 1% to 49%, and ≥ 50%, respectively. Median overall survival was 5.9 months among all patients. Among patients with known PD-L1 status, median survival was 1.6 months in those with PD-L1 < 1% vs not reached in PD-L1–positive patients, with 52% of these patients remaining alive at 1 year.

Adverse Events

Grade ≥ 3 adverse events occurred in 29 patients (69%) and were considered related to treatment in 4 (10%; anemia in 2, rash in 1, and metastases to the central nervous system in 1). The most common treatment-related adverse events of any grade were diarrhea (in 12% of patients), pruritus (12%), fatigue (7%), and pyrexia (7%). Treatment-related immune-mediated adverse events, predominantly grade 1 or 2, occurred in 10 patients (24%) and included pruritus, diarrhea, rash, increased thyroid-stimulating hormone, and hypothyroidism.

The investigators concluded, “To our knowledge, this is the first clinical trial to show responsiveness of anaplastic thyroid carcinoma to PD-1 blockade.”

Dr. Capdevila, of Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Novartis Pharmaceuticals. For full disclosures of the study authors, visit ascopubs.org.