During the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid, Spain, data from different studies assessing pembrolizumab in several types of cancer showed promising activity and safety profiles.
Pembrolizumab is a monoclonal antibody that can block both PD-L1 and PD-L2, two negative co-stimulatory receptors found on the surface of tumor cells. Upon binding to its PD-1 receptor, present in activated T lymphocytes, these ligands inhibit the effector function of immune cells, allowing cancer cells to proliferate without an effective immune surveillance.
In a study presented by Prof. Edward Garon of the David Geffen School of Medicine at UCLA, Santa Monica, USA, 282 patients who had their PD-L1 tumor levels measured, and who were either treatment-naïve or had previously treated advanced non-small cell lung cancer (NSCLC) enrolled in the Phase I KEYNOTE-001 trial.
Pembrolizumab was administered at 2 mg/kg every 3 weeks (Q3W), 10 mg/kg Q3W, or 10 mg/kg Q2W until progression, death, or unacceptable toxicity.
The researchers concluded that pembrolizumab was tolerable and had an efficient anti-tumor activity in treatment-naïve or previously treated advanced NSCLC, independent of dose or schedule. Furthermore, patients with a high PD-L1 tumor expression had an increase benefit from pembrolizumab treatment.
Dr. Caroline Robert of the Institute Gustave Roussy, Villejuif, France, presented clinical data form the KEYNOTE-001 trial relative to pembrolizumab use in melanoma patients. She showed that this therapy had the same efficacy and safety independent of dosage in patients with advanced melanoma.
Pembrolizumab has been recently approved in the United States for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor.
Dr. Kei Muro of the Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan, presented results from a Phase Ib study assessing the safety, tolerability, and anti-tumor activity of pembrolizumab in gastric cancer patients.
The team determined PD-L1 expression on tumor samples from patients who suffered from recurrent and/or metastatic adenocarcinoma of the stomach or gastroesophageal junction, with eligible patients receiving pembrolizumab 10 mg/kg every 2 weeks for up to 24 months or until complete response, disease progression, or unacceptable toxicity.
The results demonstrated that pembrolizumab was well tolerated and provided efficient anti-tumor activity in patients with advanced gastric cancer that expressed PD-L1.
Results from the KEYNOTE-012 study, assessing the safety, tolerability, and anti-tumor activity of pembrolizumab in patients with recurrent or metastatic urothelial cancer, were presented by Dr. Elizabeth Plimack of the Oncology, Fox Chase Cancer Center, Philadelphia, USA.
Again, patients who had PD-L1 expression on their tumor cells were treated with pembrolizumab, with data so far showing promising safety, tolerability and anti-tumor activity in patients with advanced urothelial cancer.
Altogether, these results provide enough evidence to continue research on pembrolizumab, especially in patients who express significant levels of PD-L1 on the surface of their cancer cells.