Clin Cancer Res. 2021 Apr 21:clincanres.0159.2021. doi: 10.1158/1078-0432.CCR-21-0159. Online ahead of print.
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: Previously treated advanced SBA patients received pembrolizumab 200 mg IV q3 weeks until disease progression (PD), toxicity, or 35 dose 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: 40 patients were treated for a median duration of 4 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 (AE, 5%). Three confirmed partial responses (PR) (8%; 95% CI: 2-20) did not meet pre-defined success criteria of ORR 30%. Median OS 7.1 mo (95% CI: 5.1-17.1) and median PFS 2.8 mo (95% CI: 2.7-4.2) were similar across primary tumor sites. One confirmed PR (3%) was seen in MSS/MSI-low patients and correlated with high tumor mutation burden (TMB). 50% of MSI-H patients achieved PR and remain alive without progression. 25 patients (63%) had grade >=3 AEs, 11 pts (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.
PMID:33883178 | DOI:10.1158/1078-0432.CCR-21-0159
