Pembrolizumab/Lanreotide Combo Confers Antitumor Activity in GEP-NETs

Pembrolizumab (Keytruda) plus lanreotide (Somulatine Depot) elicited a stable disease (SD) rate of 39% in patients with advanced, progressive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), according to findings from the phase 1b/2 PLANET study that were presented at the 2021 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancer Symposium.

No new safety signals were identified in the study.

“Pembrolizumab has antitumor activity in a subset of GEP-NETs patients,” wrote the investigators. “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 GEP-NETs.”

In the phase 1b/2 PLANET study (NCT03043664), 22 GEP-NETs patients with a median of 2 prior systemic therapies (range 1-9) were treated with 90 mg of lanreotide and 200 mg of pembrolizumab every 3 weeks until disease progression or intolerable toxicity. A median of 6 doses of pembrolizumab (range 2-15) and 7 doses of lanreotide (range 2-15) were administered.

Median age at the time of enrollment was 60.9 years (range 51.1-82.0), 12 patients were male, 10 were female. To be eligible for the study, participants were required to meet the following criteria:

• Non-resectable, recurrent, or metastatic well- or moderately-differentiated GEP-NETs with disease progression in the last 12 months

• Prior somatostatin analogue therapy
• At least one measurable lesion based on RECIST 1.1
• ECOG performance status of 0 or 1 and adequate organ function
• Tumor mitotic rate of ≤20/10 hpf and/or Ki67 index ≤20%

Fourteen patients (63.6%) had tumors located within the gastrointestinal tract, of whom 8 patients (36.4%) had their primary tumor site located in the pancreas. Median time since diagnosis for all patients was 5.3 years, with 6 patients having received prior locoregional therapy and 3 patients receiving prior external beam therapy. Of the 12 tumors that were analyzed, 4 had detectable PD-L1 expression and 11 had tumor infiltrating lymphocytes.

The primary end point of the study was overall response rate (ORR), measured according to RECIST 1.1 criteria. Fifty-two percent of patients had progressive disease (PD). ORR, as measured by irRECIST to better assess the effect of immunotherapeutic agents, was 43% SD, 48% PD, with 9% of patients not evaluable.

Secondary end points were progression-free survival (PFS) and overall survival (OS). The median PFS was 5.4 months (95% CI, 1.7-8.3) and median OS at a median follow-up of 15 months was not reached.

Regarding safety, 6 of the 22 patients (27.3%) experienced treatment-related serious adverse events (AEs) including abdominal pain, pneumonitis, colitis, and hyperglycemia, which were all related to treatment with pembrolizumab. The most common treatment-related AE was hypothyroidism (23%), with other notable treatment-related AEs including colitis (9%), hyperglycemia (14%), and pneumonitis (5%). Three patients (13.6%) discontinued treatment due to AEs.

Investigators noted that peripheral blood immune analyses were pending and would be reported subsequently.

“Further studies to identify other approaches to increase the immunogenicity of well/moderately differentiated GEP-NETs are required,” concluded the investigators.

Reference

Morse M, Halperin DM, Uronis HE, et al. Phase Ib/II study of pembrolizumab with lanreotide depot for advanced, progressive gastroenteropancreatic neuroendocrine tumors (PLANET). Presented at: 2021 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium. Abstract 369.