Keytruda (pembrolizumab) may benefit patients with with malignant pleural mesothelioma by targeting tumors that produce the immune checkpoint molecule PD-L1, according to an interim analysis of a Phase 1b study. The treatment also showed a good safety profile in this patient group.
A clinical benefit of 40 percent observed during the study — including both partial responses and a stable disease for six months or more — support further exploration of Keytruda as a treatment option in mesothelioma.
The study, “Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial,” was published in the journal The Lancet Oncology.
The Phase 1b clinical trial (NCT02054806) — led by researchers at the University of Pennsylvania Health System — screened previously treated patients with solid-tumor PD-L1-positive malignant pleural mesothelioma, and recruited 25 patients from six countries. The study was an open-label trial, where all patients received the active drug. Participants were treated with 10 mg/kg every two weeks for up to two years, or until disease progression or unacceptable side effects occurred.
Keytruda is a cancer immunotherapy that blocks the immune checkpoint molecule PD-1. Also known as anti-PD-1, Keytruda has been approved for other cancer forms (including a type of non-small cell lung cancer). The treatment is used when a tumor produces PD-L1 — the factor that binds to and activates PD-1.
The analysis showed that five patients (20%) reported a partial response, according to RECIST criteria — a set of rules that define when a tumor improves, remain stable, or worsens. In addition, 52 percent (13 patients) reported a stable disease state (no increase in the extent of the tumor). Fourteen (56%) of 23 patients showed a reduction in tumor size. Two patients continued treatment after the study.
Patients were followed for a median of 18.7 months, and the median duration of response was 12 months. Three patients had an ongoing response at the time of data analysis. Progression-free survival in the study was 5.4 months. Median overall survival was 18 months.
Researchers also analyzed the treatment’s safety, noting that 16 patients (64%) reported treatment-related adverse events. The most common side effects were fatigue, nausea, joint pain, skin itching, decreased appetite, and dry mouth. Moderately severe side effects were noted in 20 percent of participants, and included reduced blood cell counts, fever, and eye inflammation. None of the participants stopped the treatment because of treatment-related complications.
The researchers concluded that Keytruda is well-tolerated and shows possible anti-tumor activity, warranting further research.
The trial was sponsored by Merck, Keytruda’s manufacturer.
