ESMO 2017: First KEYNOTE-028 Report of Pembrolizumab Activity in Patients with PD-L1-positive pNETs and Carcinoid Tumours

Some heavily-pretreated patients derive clinical benefit from single agent pembrolizumab treatment

Pembrolizumab provided 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 carcinoid and pNET cohorts of the KEYNOTE-028 study reported at ESMO 2017, the Annual Congress of the European Society for Medical Oncology in Madrid, Spain.

PD-L1 expression is associated with higher tumour grade in patients with advanced carcinoid/neuroendocrine tumours.

Lead author Janice M. Mehnert of the Phase I and Developmental Therapeutics Program, Rutgers Cancer Institute of New Jersey in New Brunswick, USA presented findings from the pNETs and carcinoid cohorts of the multicohort phase 1b KEYNOTE-028 study (NCT02054806), which evaluated the safety and efficacy of pembrolizumab in patients with PD-L1–positive advanced solid tumours.

The study enrolled patients with PD-L1-positive carcinoid tumours or well- or moderately differentiated pNETs, ECOG PS ≤1 that had failed standard therapy. The benchmark of PD-L1–positivity was set at ≥1% modified proportion score or interface pattern, according to immunohistochemistry using QualTek.

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) per RECIST v1.1 by investigator review.

Most patients achieved stable disease with pembrolizumab

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 ECOG PS was 1 in 38% and 76% of patients, and 50% and 44% of patients with pNETs and carcinoid tumours, respectively, had received ≥2 prior therapies for metastatic disease.

The median follow-up was 20.1 (range 4.5 to 30.4) months in the pNET cohort and 18.9 (range 2.0 to 33.3) months in the carcinoid cohort. Objective responses were observed in one (6%) patient with pNET (95% confidence interval [CI] 0%, 30%) and in 3 (12%) carcinoid patients (95% CI 3%, 31%). 

Fourteen (88%) patients with pNETs and 15 (60%) patients with carcinoid tumours achieved stable disease (SD). Among responding patients, the durations of response were 17.6 months in the one responding patient with pNET and 6.9, 9.2, and 11.1 months for the carcinoid lung, gut, and other locations, respectively.

Treatment-related adverse events (TRAEs) were reported in 11 (69%) patients with pNET, including fatigue in 38% and diarrhoea in 25% of patients with pNETs. TRAEs occurred in 17 (68%) patients with carcinoid tumours that included diarrhoea in 28%, and fatigue in 20% of patients.

Grade ≥3 TRAEs occurred in 8 (32%) carcinoid patients that included 3 patients with diarrhoea, and 2 patients each with AST and ALT increased.

No pNETs patients had grade ≥3 TRAEs.

One grade 4 nontreatment-related adverse event of increased gamma-glutamyl transferase and one death of unspecified cause that also was unrelated to treatment occurred in the carcinoid cohort.

Conclusions

Pembrolizumab was generally well tolerated in patients with heavily pretreated carcinoid or pNET tumours, and provided clinically meaningful antitumour activity in some patients, the authors summarised.

Dr Ian Chau, Consultant Medical Oncologist of The Royal Marsden Hospital, London & Surrey, UK who discussed the study results said that moving to new targets in neuroendocrine tumours shows encouraging steps in clinical trials. It is about first results in prospective anti-PD1 antibody study. He questioned if PD-L1 is a good biomarker for pembrolizumab sensitivity for NETs.

Disclosure

The study was supported by Merck & Co., Inc., Kenilworth, NJ, USA.

Reference

427O – Mehnert JM, et al. Pembrolizumab for patients with PD-L1–positive advanced carcinoid or pancreatic neuroendocrine tumors: results from the KEYNOTE-028 study.