Lanreotide combined with pembrolizumab led to stable disease with acceptable safety in nearly 40% of patients with  gastroenteropancreatic neuroendocrine tumors (GEPNETs), according to a phase 2 trial presented by Michael Morse, MD, Professor of Medicine, Duke Cancer Institute, Durham, NC, at the 2021 ASCO Gastrointestinal Cancers Symposium (J Clin Oncol 39, 2021 [suppl 3; abstr 369]).

“Pembrolizumab has antitumor activity in a subset of GEPNETs patients. We hypothesized that the lanreotide, by its antitumor effects and reduction of serotonin, a modulator of immunity, would synergize with pembrolizumab in low/intermediate grade GEPNETs,” explained Morse and colleagues. 

Researchers administered lanreotide 90mg and pembrolizumab 200 mg to GEP-NETs patients who had previously progressed on somatostatin analogues every 3 weeks, until disease progression or intolerable toxicity occurred. The median pembrolizumab and lanreotide doses administered were 6 and 7, respectively.

The primary end point was objective response rate (ORR), and secondary end points included progression-free survival (PFS) and overall survival (OS).

Of the 22 patients treated (GI/pancreatic, 14/8; median Ki67, 5%; median time since diagnosis, 5.3 yrs), prior octreotide LAR was administered to 20, while one had previously received lanreotide and the other received both. Patients had a median of two prior systemic therapies (range 1-9); six patients had undergone locoregional therapy and three had external beam radiotherapy. Of the 12 tumors analyzed so far, four had detectable PD-L1 expression, 11 had detectable tumor-infiltrating lymphocytes.

The median overall survival at a median follow-up of 15 months was not reached, and the median PFS was 5.4 months (95% CI, 1.7-8.3). The best responses by RECIST 1.1 were stable disease in 39% of patients and progressive disease in 52%; responses from immune response RECIST were stable disease and progressive disease in 43% and 48% of patients, respectively.

Treatment-related serious adverse events (AEs) including abdominal pain, pneumonitis, colitis, and hyperglycemia occurred in six patients. All serious AEs were related to pembrolizumab. Other treatment-related events were hypothyroidism(23%), colitis(9%), hyperglycemia (14%), and pneumonitis(5%).

“In a population of GEPNET patients, progressing on a median of 2 prior therapies, including prior somatostatin analogue therapy, a minority of whom had PD-L1 expressing tumors, the combination of lanreotide and pembrolizumab produced stable disease in approximately 40% of patients. No new safety signals were identified,” concluded Dr Morse et al. —Alexandra Graziano