Increased cancer cell growth

Pembrolizumab Effective in Thymic Carcinoma

Thymic carcinoma is a rare, aggressive cancer with few treatment options. Chemotherapy is the primary treatment for metastatic thymic carcinoma, but it is associated with high rates of relapse. Targeted therapies, with the exception of sunitinib, have been largely unsuccessful treatments for this disease. Thymic carcinomas have high PD-L1 expression, making immunotherapy with anti–PD-1/PD-L1 antibodies an attractive treatment option. In a single institution phase II study, the safety and efficacy of the PD-1 inhibitor pembrolizumab (200 mg every 3 weeks for up to 2 years) was examined in 40 patients with metastatic thymic carcinoma who had progressed following at least one line of chemotherapy.

At a median follow-up of 20 months, 22.5% of patients treated with pembrolizumab had responded to treatment, including 1 complete response (CR) and 8 partial responses (PRs). In patients with either CR or PR, the median duration of response was 22.4 months. For patients in whom the best response was stable disease, responses lasted for a median of 6.8 months. At 1 year, the estimated rates of progression-free survival (PFS) and overall survival (OS) were 29% and 71%, respectively. Median PFS was 4.2 months and median OS was 24.9 months.

An exploratory analysis of PD-L1 expression by immunohistochemistry (IHC) found that 10 patients (25%) had PD-L1 levels ³50%. Six of these patients achieved either partial or complete response. PFS and OS were both longer in patients with high PD-L1 expression compared to those with low or no PD-L1 expression. In addition, there was a significant correlation between presence of the 18-gene interferon-γ signature and response (P = .044).

The adverse events (AEs) associated with pembrolizumab were mostly grade 1/2 and consistent with the known safety profile of this agent in other tumors. Increased liver aspartate aminotransferase and alanine aminotransferase were the most common grade 3/4 AE (13% each). Of note, severe autoimmune toxicity occurred in 6 patients (15%), including 2 patients (5%) with myocarditis, requiring high-dose steroids and placement of a pacemaker. However, there were no deaths due to toxicity.

The investigators concluded that pembrolizumab is a safe and effective treatment for recurrent thymic carcinoma. However, due to increased risk of developing severe autoimmune toxicity, patients with thymic carcinoma should be carefully monitored while undergoing treatment.

Lancet Oncol. 2018 January 25. [Epub ahead of print].


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