Second-line Pembrolizumab Shows ‘Encouraging’ PFS for Advanced Mesothelioma

Second-line pembrolizumab monotherapy exhibits clinical activity and is associated with “encouraging” progression-free survival (PFS) rates among patients with programmed cell death protein 1 ligand (PD-L1)-positive, locally-advanced or metastatic malignant pleural mesothelioma, according to authors of the nonrandomized multicohort phase Ib KEYNOTE-028 clinical study. The findings were presented at the 2015 World Conference on Lung Cancer in Denver.¹

As of June 24, 2015, partial response had been reported for seven of 25 study participants with PD-L1-positive malignant pleural mesothelioma, of which four were ongoing. Twelve patients had stable disease.

“Single-agent pembrolizumab has significant clinical activity in patients with PD-L1-positive MPM [malignant pleural mesothelioma],” said lead study author Evan Alley, MD, PhD, Chief of the Division of Hematology and Medical Oncology at the Penn Presbyterian Medical Center, the University of Pennsylvania in Philadelphia.

“The 28% overall response rate and the 76% disease-control rate are better than historical response rates for second-line therapy,” he noted.

Median PFS was 5.8 months (95% CI, 3.4–8.2) and the 6-month PFS rate was an “encouraging” 50.0%, Dr. Alley reported.

Immunohistochemistry-determined PD-L1 expression levels did not predict the tumor response to pembrolizumab (P = .284), he noted.

Patients were administered pembrolizumab (10 mg/kg) every 2 weeks and response was assessed every 8 weeks for 6 months, and then every 12 weeks. Treatment continued for up to 2 years or until disease progression or unacceptable toxicity.

At a median followup of 11.5 months (range, 1.4–13.1 months), the most common adverse events (AE) were fatigue (24% of patients), nausea (24%), arthralgia (20%), and pruritus (16%). Grade 3/4 treatment-related AEs affecting one patient each, included elevated alanine aminotransferase, thrombocytopenia, iridocyclitis (uveitis), and pyrexia.

Expression of PD-L1, which binds to PD-1, is associated with poor prognosis among patients with malignant pleural mesothelioma. Pembrolizumab (MK-3475) is a humanized monoclonal antibody immune checkpoint inhibitor that targets the PD-1 receptor to allow antitumor immune response. It is currently indicated in the United States at an intravenous dose of 2 mg/kg, infused over 30 minutes, every 3 weeks, following progression of unresectable or metastatic melanoma following treatment with ipilimumab (and a BRAF inhibitor in patients whose tumors harbor a BRAF V600 mutation).

Further study is ongoing with a phase II trial (NCT02399371), Dr. Alley said. The study was funded by Merck, which is conducting or has planned more than 100 clinical trials for pembrolizumab as a monotherapy, or as a component of combination therapies for more than 30 tumor types.

References:

• Alley EW, Schellens JH, Santoro A, et al. (2015). Single-Agent Pembrolizumab for Patients with Malignant Pleural Mesothelioma (MPM). International Association for the Study of Lung Cancer, 16^th World Conference on Lung Cancer September 6-9, 2015.