Pembrolizumab in PD-L1–Positive Malignant Pleural Mesothelioma


Key Points

  • In patients with malignant pleural mesothelioma, response to pembrolizumab was observed in 20% of patients.
  • The median duration of response was 12 months.

In an interim analysis of the phase IB KEYNOTE-028 trial reported in The Lancet Oncology, Alley et al found that pembrolizumab (Keytruda) treatment produced durable responses in patients with malignant pleural mesothelioma.

Study Details

The current report involves 25 patients with previously treated programmed cell death ligand 1 (PD-L1)–positive disease in a cohort of the ongoing trial, which includes patients with other advanced PD-L1–positive solid tumors. Patients form 13 sites in 6 countries received pembrolizumab at 10 mg/kg every 2 weeks for up to 2 years or until disease progression or unacceptable toxicity. PD-L1 positivity was defined as expression in ≥ 1% of tumor cells on immunohistochemistry.

Patients had a median age of 65 years, 68% were men, 84% were white, all had an Eastern Cooperative Oncology Group performance status of 0 or 1, histology was epithelioid in 72%, 32% had received at least 2 prior lines of therapy, and prior therapy included a platinum in 88% and pemetrexed (Alimta) in 84%.

Responses and Toxicity

Responses (all partial responses) were observed in 5 patients (20%, 95% confidence interval [CI] = 6.8%–40.7%), and 13 patients (52%) had stable disease. The median duration of response was 12.0 months (95% CI = 3.7 months to not reached), with 2 responders remaining on treatment at data cutoff in June 2016.

The most common treatment-related adverse events of any grade were fatigue (24%), nausea (24%), and arthralgia (20%). Treatment-related grade 3 adverse events occurred in 5 patients (20%), consisting of dyspnea, decreased appetite, pyrexia, alanine transaminase increase, and iridocyclitis in 1 (4%) each. Immune-related adverse events led to treatment interruption in 3 patients (12%); they consisted of grade 3 rhabdomyolysis and grade 2 hypothyroidism in 1; grade 3 iridocyclitis, grade 1 erythema multiforme, and grade 3 erythema in 1; and grade 2 infusion-related reaction in 1. No treatment-related discontinuations of treatment and no treatment-related deaths were observed.

The investigators concluded: “Pembrolizumab appears to be well tolerated and might confer anti-tumour activity in patients with PD-L1-positive malignant pleural mesothelioma. Response durability and efficacy in this patient population warrant further investigation.”

The study was supported by Merck.

Evan W. Alley, MD, of Penn Presbyterian Medical Center, University of Pennsylvania Health System, is the corresponding author of The Lancet Oncology article.

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