2019 GI Cancers Symposium: Pembrolizumab in Pretreated, Advanced Neuroendocrine Tumors
Findings from the phase I KEYNOTE-028 trial, which studied pembrolizumab in a number of solid tumors, showed activity of the immunotherapy in some patients with heavily pretreated neuroendocrine tumors. Now, a phase II basket trial—KEYNOTE-158—is studying the efficacy and safety of pembrolizumab in 10 different tumor types, including neuroendocrine tumors. At the 2019 Gastrointestinal Cancers Symposium, Strosberg et al presented an analysis of 107 patients from the neuroendocrine cohort of KEYNOTE-158 (Abstract 190).
Analysis Methods
Eligibility criteria for the cohort included well-differentiated and moderately differentiated neuroendocrine tumors of the lung, appendix, small intestine, colon, rectum, or pancreas; disease progression on or intolerance to at least 1 line of standard therapy; ECOG performance score of 0 or 1; and a tumor sample for biomarker analysis.
Patients received 200 mg of pembrolizumab every 3 weeks for 2 years or until progression, intolerable toxicity, or physician or patient decision. Programmed cell death ligand 1 (PD-L1) positivity was evaluated by immunohistochemistry retrospectively. Tumor imaging was performed every 9 weeks for the first year and then every 12 weeks.
The median age of patients enrolled was 59 years, 44.9% had an ECOG performance score of 1, and 67.3% had received 2 or more prior therapies. Approximately 16% of participants had PD-L1–positive neuroendocrine tumors.
The primary endpoint was overall response rate. Secondary endpoints included duration of response, progression-free survival, overall survival, and safety.
Study Findings
The median follow-up was 18.6 months. The overall response rate was 3.7% (95 confidence interval [CI] = 1.0%–9.3%), with no complete responses and 4 partial responses—3 in patients with a neuroendocrine tumor of the pancreas and 1 in a patient with a gastrointestinal (unknown primary) neuroendocrine tumor. All 4 patients with responses to pembrolizumab had PD-L1–negative disease.
Sixty-one patients had stable disease as their best response. Median duration of response was not reached, with 3 of the 4 responses ongoing after 9 months of follow-up, and median overall survival was also not reached (95% CI = 18.8–not reached). The 6-month overall survival rate was 84.6%. Median progression free survival was 4.1 months (95% CI), and the 6-month progression-free survival rate was 38.2%.
Treatment-related adverse events occurred in approximately three-quarters of patients, and 20.6% of patients had grade 3/4 adverse events. The most commonly reported adverse event was fatigue (which occurred in 21.5% of patients).
The authors concluded, “Pembrolizumab monotherapy showed limited antitumor activity and manageable safety in patients with previously treated, advanced neuroendocrine tumors.”
Disclosure: The study authors' full disclosures can be found at coi.asco.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
