One patient died of treatment-related mesenteric ischemia, reported Patrick A. Ott, MD, of Dana-Farber Cancer Institute in Boston, and his associates. Nonetheless, with an objective response rate of 33% and a median duration of response of 19 months, the checkpoint inhibitor “demonstrated a favorable safety profile and promising durable clinical activity,” they concluded.
Study participants received pembrolizumab (10 mg/kg) every 2 weeks for 24 months or until disease progression or intolerable toxicity occurred. After a median follow-up of 9.8 months (range, 0.5-24 months), one patient (4%) had a complete response, and seven (29%) had partial responses. The median onset of response was 2 months, and responses lasted from 3.6 to 20 months, Dr. Ott and his associates reported (J Clin Oncol. 2017 Aug 16. doi: 10.1200/JCO.2017.72.5069). Two-thirds of patients developed treatment-related adverse events, most often arthralgia, asthenia, rash, diarrhea, and fatigue. Two patients developed grade 3 or worse treatment-related adverse events, including a 65-year-old man with small cell lung cancer and liver metastasis who developed grade 3 bilirubin elevation, and a 58-year-old woman with a history of sleeve gastrectomy who developed grade 3 asthenia, grade 5 colitis, and intestinal ischemia.
The patient who died had received 10 cycles of pembrolizumab, was hospitalized with abdominal pain, nausea, and vomiting, and was discharged home with a diagnosis of food intolerance, the researchers reported. She received an 11th cycle of pembrolizumab and was readmitted with abdominal pain. A rectal biopsy showed chronic colitis. She received systemic corticosteroids and was discharged, was admitted to a different hospital several weeks later with diffuse abdominal pain and septic shock, and subsequently died. “Mesenteric ischemia resulted in death,” the researchers wrote. “The cause of the colitis and intestinal ischemia was reported as probably related to pembrolizumab.”
Pembrolizumab (Keytruda) is a programmed death receptor–1 blocking antibody approved for treating non–small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, urothelial carcinoma, and microsatellite instability–high cancer or mismatch repair deficient solid tumors. Treatment with the checkpoint inhibitor led to grade 5 treatment-related adverse events in other trials. Most recently, in July 2017, the Food and Drug Administration placed clinical holds on phase 1 and phase 3 studies of pembrolizumab for treating multiple myeloma after more patients died in the pembrolizumab arms than did in the comparison arms. Pembrolizumab also recently came up short in a phase 3 trial of patients with head and neck cancer, although it has kept its FDA label for this indication. Multiple trials of pembrolizumab for small cell lung cancer are recruiting or ongoing.
Merck funded the study. Dr. Ott disclosed research funding from Merck and several other pharmaceutical companies, and advisory or consulting relationships with several companies, excluding Merck.