Majority of Patients With High-Grade Carcinoid or Pancreatic Neuroendocine Tumours Achieve Stable Disease with Pembrolizumab
By Jenny Powers
MADRID, Spain -- September 14, 2017 --The programmed death ligand 1 (PD-L1) inhibitor pembrolizumab provides a higher objective response and stable disease in heavily pretreated patients with high-grade pancreatic neuroendocrine tumours (pNETs) or carcinoid tumours demonstrating PD-L1 expression, according to data from the phase 1b KEYNOTE-028 study reported at the 42nd European Society for Medical Oncology (ESMO) Congress.
At a median follow-up of 20.1 months (range: 4.5 to 30.4 months) in the pNET cohort and 18.9 months (range: 2.0 to 33.3 months) in the carcinoid cohort, objective responses were observed in 1 patient (6%) with pNET (95% confidence interval [CI]: 0% to 30%) and in 3 carcinoid patients (12%) (95% CI: 3% to 31%).
Fourteen (88%) patients with pNETs and 15 (60%) patients with carcinoid tumours achieved stable disease (SD). Among responding patients, the duration of response was 17.6 months in the 1 responding patient with pNET and 6.9, 9.2, and 11.1 months for patients with carcinoid lung, gut, and other location tumours, respectively.
“PD-L1 expression is associated with higher tumour grade in patients with advanced carcinoid/neuroendocrine tumours,” explained lead author Janice M. Mehnert, MD, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, speaking here on September 10.
Dr. Mehnert presented findings from the pNETs and carcinoid cohorts of the multicohort KEYNOTE-028 study, which evaluated the safety and efficacy of pembrolizumab in patients with PD-L1-positive carcinoid tumours or well or moderately differentiated pNETs that had failed standard therapy.
Pembrolizumab was administered at 10 mg/kg every 2 weeks for up to 2 years or until confirmed progression, intolerable toxicity, or withdrawal of consent. Response was assessed every 8 weeks for the first 6 months and every 12 weeks thereafter.
The primary endpoint was objective response rate (ORR).
The benchmark for PD-L1-positivity was set at ≥1% modified proportion score or interface pattern, according to immunohistochemistry.
Of the 276 patients screened with tumour samples evaluable for PD-L1 detection, 36% were positive; of these, 16 patients had pNETs and 25 patients had carcinoid tumours that included 9 with lung, 7 with gut, and 9 patients with other tumour locations. The median ages of the patients were 61 and 63 years in the pNETs and carcinoid cohorts, respectively. The Eastern Cooperative Oncology Group (ECOG) Performance Status was 1 in 38% and 76% of patients, and ≥2 prior therapies for metastatic disease had been administered to 50% and 44% of patients with pNETs and carcinoid tumours, respectively.
“Pembrolizumab was generally well tolerated in patients with heavily pretreated carcinoid or pNET tumours, and provided clinically meaningful antitumour activity in some patients,” commented Dr. Mehnert.
Treatment-related adverse events (TRAEs) were reported in 11 (69%) patients with pNET, including fatigue in 6 patients (38%) and diarrhoea in 4 patients (25%). TRAEs occurred in 17 (68%) patients with carcinoid tumours, including diarrhoea in 7 patients (28%) and fatigue in 5 patients (20%).
Grade ≥3 TRAEs occurred in 8 (32%) carcinoid patients, including 3 patients with diarrhoea, and 2 patients each with increased aspartate aminotransferase and alanine aminotransferase. No pNETs patients had grade ≥3 TRAEs.
One grade 4 nontreatment-related adverse event of increased gamma-glutamyl transferase and 1 death of unspecified cause occurred in the carcinoid cohort; both were unrelated to treatment.
The study was supported by Merck & Co., Inc., Kenilworth, New Jersey.
[Presentation title: Pembrolizumab for Patients With PD-L1-positive Advanced Carcinoid or Pancreatic Neuroendocrine Tumors: Results From the KEYNOTE-028 Study. Abstract 427O]