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ZEBRA: A Multicenter Phase II Study of Pembrolizumab in Patients with Advanced Small-Bowel Adenocarcinoma
- Source :
- Clinical cancer research : an official journal of the American Association for Cancer Research. 27(13)
- Publication Year :
- 2021
-
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.
- Subjects :
- 0301 basic medicine
Adult
Male
Cancer Research
medicine.medical_specialty
Phases of clinical research
Pembrolizumab
Adenocarcinoma
Antibodies, Monoclonal, Humanized
Gastroenterology
03 medical and health sciences
0302 clinical medicine
FOLFOX
Duodenal Neoplasms
Internal medicine
Clinical endpoint
Medicine
Humans
Prospective Studies
Adverse effect
Immune Checkpoint Inhibitors
Aged
Neoplasm Staging
Aged, 80 and over
Jejunal Neoplasms
business.industry
Microsatellite instability
Middle Aged
medicine.disease
Primary tumor
Ileal Neoplasms
030104 developmental biology
Treatment Outcome
Oncology
030220 oncology & carcinogenesis
Female
Microsatellite Instability
business
medicine.drug
Subjects
Details
- ISSN :
- 15573265
- Volume :
- 27
- Issue :
- 13
- Database :
- OpenAIRE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Accession number :
- edsair.doi.dedup.....c303cf8770a2787ea2edb4608aebc955