{"doi":"10.1016/j.adro.2021.100807","title":"A Phase 2 Trial Combining Pembrolizumab and Palliative Radiation Therapy in Gastroesophageal Cancer to Augment Abscopal Immune Responses","abstract":"PURPOSE: Single agent PD-1 inhibitors have yielded durable responses in a minority of gastroesophageal cancers. Radiation therapy has been recognized to promote antitumor immune responses and may synergize with anti-PD-1 agents. We sought to evaluate if combining palliative radiation therapy with pembrolizumab can augment antitumor immune responses in gastroesophageal cancer. METHODS AND MATERIALS: Patients had metastatic gastroesophageal cancer with indication for palliative radiation therapy with ≥2 disease sites outside of the radiation field assessable for abscopal response and biopsies for laboratory correlative analyses. Palliative radiation was delivered to a dose of 30 Gy over 10 fractions. Pembrolizumab, 200 mg, was administered concurrently intravenously every 3 weeks until disease progression, unacceptable toxicity, or study withdrawal, for up to 2 years. Endpoints included PD-L1 expression in pre- and posttreatment biopsies and abscopal objective response rate per Response Evaluation Criteria in Solid Tumors. RESULTS: Of 14 enrolled patients, the objective response rate was 28.6% (95% confidence interval, 8.4%-58.1%), and the median duration of response was not reached (95% confidence interval, 6.9-NR months). Overall, 2 patients had treatment-related grade 3 to 4 adverse events with no grade 5 events. One patient discontinued therapy due to grade 4 colitis. We did not observe an association between radiation and abscopal changes in PD-L1 expression via assessment of an analogous PD-L1 Combined Positive Score, Tumor Proportion Score, Mononuclear Immune Cell Density Score, or proportion of PD-L1-expressing immune cells between pre- and posttreatment tumor biopsies. CONCLUSIONS: Combining palliative radiation therapy and pembrolizumab provided promising durable responses in this patient population but we were unable to definitively distinguish abscopal biologic changes. Biomarker analyses beyond PD-L1 expression are needed to better understand putative mechanisms and identify patients who will benefit from this approach.","journal":"Advances in Radiation Oncology","year":2021,"id":199382,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":444469,"name":"Ting-Fang He","orcid":null,"position":1,"is_corresponding":false},{"id":775854,"name":"Massimo D’Apuzzo","orcid":"0000-0001-8146-0997","position":2,"is_corresponding":false},{"id":775855,"name":"Yi‐Jen Chen","orcid":"0009-0009-5479-6634","position":3,"is_corresponding":false},{"id":380347,"name":"Paul Frankel","orcid":"0000-0003-2231-6121","position":4,"is_corresponding":false},{"id":776479,"name":"Michael Tajon","orcid":null,"position":5,"is_corresponding":false},{"id":273885,"name":"Helen Chen","orcid":"0000-0002-9401-7895","position":6,"is_corresponding":false},{"id":480505,"name":"Shawn T. Solomon","orcid":"0000-0002-3819-9436","position":7,"is_corresponding":false},{"id":314970,"name":"Samuel J. Klempner","orcid":"0000-0002-4062-0808","position":8,"is_corresponding":false},{"id":520892,"name":"Marwan Fakih","orcid":"0000-0002-6554-5488","position":9,"is_corresponding":false},{"id":294150,"name":"Peter P. Lee","orcid":"0000-0002-2660-4377","position":10,"is_corresponding":false},{"id":505233,"name":"Joseph Chao","orcid":"0000-0002-1809-504X","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-18T23:50:40.558460Z","pmid":"35071830","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}