Pembrolizumab Active in Thymic Carcinoma

Giuseppe Giaccone, MD, PhD

Pembrolizumab (Keytruda) induced responses in more than one-fifth of patients with recurrent thymic carcinoma who had progressed following 1 or more lines of chemotherapy, according to findings from a phase II trial published in The Lancet Oncology.

Results from the single-arm, single-site study showed that at a median follow-up of 20 months, the response rate was 22.5% (95% CI, 10.8-38.5). One (3%) patient achieved a complete response, 8 (20%) had partial responses, and 21 (53%) had stable disease.

The disease control rate was 75% (95% CI, 59-87) and the median time to response was 6 weeks (range, 6-24; IQR, 6-12). There were no cases of pseudoprogression.

“To the best of our knowledge, these findings represent the first prospective data to demonstrate the antitumour activity of anti—PD-1 therapy in pretreated metastatic thymic carcinoma,” first author Giuseppe Giaccone, MD, PhD, associate director for Clinical Research with the Georgetown Lombardi Comprehensive Cancer Center, and colleagues wrote. “Given the relative paucity of effective systemic therapies in the setting of metastatic disease, pembrolizumab might represent a new therapeutic option for these patients.”

Forty-one patients were enrolled at the Georgetown Lombardi Comprehensive Cancer Center from March 2015 to December 2016. Most had received more than 1 previous line of chemotherapy and had extensive metastatic disease. One patient was excluded because of elevated liver enzymes at screening.

All patients were assigned to 200 mg of pembrolizumab every 3 weeks for up to 2 years, and dose reductions were not allowed. The data cutoff date was July 28, 2017.

The median progression-free survival (PFS) was 4.2 months (95% CI, 2.9-10.3) and the median overall survival (OS) was 24.9 months (95% CI, 15.5-not reached). The 1-year PFS rate was 29% (95% CI, 17.6-48.5) and the 1-year OS rate was 71% (95% CI, 57.6-87.1).

The median duration of response for the 9 patients with a complete or partial response was 22.4 months (95% CI, 12.3-34.7). The median duration of stable disease in the 21 patients with stable disease was 6.8 months (95% CI, 1.8-11.7). Eight patients (20%) maintained stable disease for at least 6 months, and 3 patients had stable disease that was maintained for more than a year.

PD-L1 immunohistochemistry data were available for 37 patients. Ten patients (20%) displayed high PD-L1 expression (≥50%). Six of these patients had a partial or complete response (P = .005), 5 had disease progression, and 1 died. Of the 27 patients with low PD-L1 expression, 23 had disease progression and 14 died.

In a posthoc analysis, median PFS was longer in patients with high PD-L1 expression compared with patients with low or no expression (24 vs 2.9 months). Median OS also favored patients with high expression (not reached vs 15.5 months).

At the cutoff date, 31 patients (78%) had disease progression. Seventeen (43%) patients had died by that date, 14 of disease progression and 1 each of heart failure, the toxic effects of subsequent treatment, and development of acute myeloid leukemia.

Patients received a median of 6 cycles (range, 1-35) of treatment. Disease progression (70%) was the primary reason for discontinuation. The most common grade 3/4 adverse events were increased AST and ALT levels (13% each).

Investigators noted that 6 patients (15%) developed at least 1 new-onset severe immune-related adverse event (irAE). Four of these patients were treated with 125 mg of methylprednisolone followed by 1 to 2 mg/kg of prednisone daily or 4 mg of dexamethasone every 4 hours. Four patients were hospitalized, but no patient with severe irAEs died because of toxicity. Three patients with severe irAEs required dose interruptions.

Giaccone G, Kim C, Thompson J, et al. Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study [published online January 26, 2018]. Lancet Oncol. doi: 10.1016/S1470-2045(18)30062-7.