Efficacy and Safety of Pembrolizumab for Heavily Pretreated Patients With Advanced, Metastatic Adenocarcinoma or Squamous Cell Carcinoma of the Esophagus: The Phase 2 KEYNOTE-180 Study.
Abstract | IMPORTANCE: Effective treatment options are limited for patients with advanced, metastatic esophageal cancer progressing after 2 or more lines of systemic therapy. OBJECTIVE: DESIGN, SETTING, AND PARTICIPANTS: This phase 2, open-label, interventional, single-arm study, KEYNOTE-180, enrolled 121 patients from January 12, 2016, to March 21, 2017, from 57 sites in 10 countries. Patients had advanced, metastatic esophageal cancer that progressed after 2 or more lines of therapy and had evaluable tumor samples for biomarkers. INTERVENTIONS:
Pembrolizumab, 200 mg, was administered intravenously every 3 weeks until disease progression, unacceptable toxic effects, or study withdrawal, for up to 2 years. MAIN OUTCOMES AND MEASURES: Primary end point was objective response rate per the Response Evaluation Criteria in Solid Tumors by central imaging review for all patients. RESULTS: As of September 18, 2017, of 121 enrolled patients (100 men and 21 women; median age, 65 years [range, 33-87 years]), 18 (14.9%) had undergone 3 or more prior therapies, 63 (52.1%) had ESCC, and 58 (47.9%) had tumors positive for programmed death ligand-1 (PD-L1), defined as a combined positive score of 10 or higher assessed by immunohistochemistry. Median duration of follow-up was 5.8 months (range, 0.2-18.3 months). Objective response rate was 9.9% (95% CI, 5.2%-16.7%) among all patients (12 of 121), and median duration of response was not reached (range, 1.9-14.4 months). Objective response rate was 14.3% (95% CI, 6.7%-25.4%) among patients with ESCC (9 of 63), 5.2% (95% CI, 1.1%-14.4%) among patients with adenocarcinoma (3 of 58), 13.8% (95% CI, 6.1%-25.4%) among patients with PD-L1-positive tumors (8 of 58), and 6.3% (95% CI, 1.8%-15.5%) among patients with PD-L1-negative tumors (4 of 63). Overall, 15 patients (12.4%) had treatment-related grade 3 to 5 adverse events. Only 5 patients (4.1%) discontinued treatment because of adverse events. There was 1 treatment-related death from pneumonitis. CONCLUSIONS AND RELEVANCE: TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02559687.
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Authors | Manish A Shah, Takashi Kojima, Daniel Hochhauser, Peter Enzinger, Judith Raimbourg, Antoine Hollebecque, Florian Lordick, Sung-Bae Kim, Masahiro Tajika, Heung Tae Kim, A Craig Lockhart, Hendrik-Tobias Arkenau, Farid El-Hajbi, Mukul Gupta, Per Pfeiffer, Qi Liu, Jared Lunceford, S Peter Kang, Pooja Bhagia, Ken Kato |
Journal | JAMA oncology
(JAMA Oncol)
Vol. 5
Issue 4
Pg. 546-550
(Apr 01 2019)
ISSN: 2374-2445 [Electronic] United States |
PMID | 30570649
(Publication Type: Clinical Trial, Phase II, Journal Article)
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Chemical References |
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents, Immunological
- B7-H1 Antigen
- Biomarkers, Tumor
- CD274 protein, human
- pembrolizumab
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Topics |
- Adenocarcinoma
(drug therapy, metabolism)
- Adult
- Aged
- Aged, 80 and over
- Antibodies, Monoclonal, Humanized
(adverse effects, therapeutic use)
- Antineoplastic Agents, Immunological
(adverse effects, therapeutic use)
- B7-H1 Antigen
(metabolism)
- Biomarkers, Tumor
(metabolism)
- Esophageal Neoplasms
(drug therapy, metabolism)
- Esophageal Squamous Cell Carcinoma
(drug therapy, metabolism)
- Female
- Humans
- Male
- Middle Aged
- Treatment Outcome
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