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Clin Cancer Res ; 27(13): 3641-3648, 2021 07 01.
Article in English | MEDLINE | ID: mdl-33883178

ABSTRACT

PURPOSE: Small-bowel adenocarcinoma (SBA) is rare, and no standard of care exists for metastatic disease beyond first-line FOLFOX/CAPOX. SBA has higher rates of microsatellite instability (MSI-H) and T-lymphocyte infiltration than other gastrointestinal cancers. We hypothesize that pembrolizumab, a PD-1 inhibitor, will induce antitumor response. PATIENTS AND METHODS: Patients with previously treated advanced SBA received pembrolizumab 200 mg i.v. every 3 weeks until disease progression (PD), toxicity, or 35 doses maximum. Primary endpoint was confirmed overall response rate (ORR) with secondary progression-free survival (PFS), overall survival (OS), and toxicity assessment endpoints. Outcomes were stratified by tumor location, microsatellite stability (MSS) or instability (MSI-H), and PD-L1 level. RESULTS: Forty patients were treated for a median duration of four cycles (range, 1-35). All patients are off study treatment due to PD (75%), death (10%), 35 cycles completed (8%), refusal (3%), and adverse effects (AEs, 5%). Three confirmed partial responses [PRs; 8%; 95% confidence interval (CI), 2-20] did not meet predefined success criteria of ORR 30%. Median OS (7.1 months; 95% CI, 5.1-17.1) and median PFS (2.8 months; 95% CI, 2.7-4.2) were similar across primary tumor sites. One confirmed PR (3%) was seen in patients with low MSS/MSI tumors and correlated with high tumor mutation burden (TMB). Fifty percent of patients with MSI-H tumors achieved PR and remain alive without progression. Twenty-five patients (63%) had grade ≥3 AEs and 11 patients (28%) had grade 4/5 AEs. CONCLUSIONS: In the largest study of SBA to date, pembrolizumab did not induce the hypothesized response rate; however, we did identify responses in key biomarker-selected cohorts.


Subject(s)
Adenocarcinoma/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Duodenal Neoplasms/drug therapy , Ileal Neoplasms/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Jejunal Neoplasms/drug therapy , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Duodenal Neoplasms/genetics , Duodenal Neoplasms/pathology , Female , Humans , Ileal Neoplasms/genetics , Ileal Neoplasms/pathology , Jejunal Neoplasms/genetics , Jejunal Neoplasms/pathology , Male , Microsatellite Instability , Middle Aged , Neoplasm Staging , Prospective Studies , Treatment Outcome
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