{"doi":"10.1093/jnci/djae297","title":"First cycle toxicity and survival in patients with rare cancers treated with checkpoint inhibitors","abstract":"BACKGROUND: Associations between immune-related adverse events from checkpoint inhibitor therapy and outcomes have been previously evaluated, with most prior research finding a positive association between toxicity and survival. This prior research has generally reported on more common tumor types. We use a unique data resource of a federally funded basket trial (NCT02834013) for patients with rare cancers (n = 684) to evaluate associations between immune-related adverse events and overall survival and progression-free survival (PFS). METHODS: Patients were treated with nivolumab and ipilimumab; the trial was opened at more than 1000 sites. Landmark Cox regression models were used to assess first cycle immune-related adverse event associations with PFS and overall survival. RESULTS: We found that grade 1-2 treatment-related immune-related adverse events in the first cycle of therapy were associated with longer overall survival (multivariable hazard ratio [HR] = 0.61, 95% confidence interval [CI] = 0.49 to 0.75; P < .001) compared with no treatment-related immune-related adverse event, while grade 3-4 immune-related adverse events were associated with shorter overall survival (HR = 1.41, 95% CI = 1.04 to 1.90; P = .025). Similar but weaker associations were observed with PFS and grade 1-2 treatment-related immune-related adverse events (HR = 0.83, 95% CI = 0.67 to 1.01; P = .067) and grade 3-4 (HR = 1.35, 95% CI = 1.02 to 1.78; P = .037) compared with no treatment-related immune-related adverse events. Grade 1-2 dermatologic toxicity was associated with improved overall survival compared with other grade 1-2 toxicities (HR = 0.67, 95% CI = 0.52 to 0.85; P = .002). There was no statistically significant overall survival difference between patients with grade 1-2 fatigue, gastrointestinal, metabolic, hepatic, endocrine, and thyroid toxicities vs other grade 1-2 toxicities. CONCLUSION: In this large cohort of patients with rare tumors receiving checkpoint inhibitor therapy, grade of immune-related adverse event in the first cycle was predictive for survival.","journal":"JNCI Journal of the National Cancer Institute","year":2024,"id":443701,"datarank":0.3854249221750526,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.05584123557461964,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.05584123557461964,"corpus_percentile":52.850622727624355,"corpus_rank":6096,"citation_count":8,"citer_count":6,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.8806,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":110451,"name":"Sandip Pravin Patel","orcid":"0000-0002-8387-4840","position":1,"is_corresponding":false},{"id":251015,"name":"Young Kwang Chae","orcid":"0000-0003-1557-7235","position":2,"is_corresponding":false},{"id":1013749,"name":"Eliana Dietrich","orcid":"0009-0000-8836-0374","position":3,"is_corresponding":false},{"id":262227,"name":"Howard Streicher","orcid":"0000-0003-3683-9804","position":4,"is_corresponding":false},{"id":262226,"name":"Elad Sharon","orcid":"0000-0002-0044-9719","position":5,"is_corresponding":false},{"id":108759,"name":"Razelle Kurzrock","orcid":"0000-0003-4110-1214","position":6,"is_corresponding":false},{"id":383952,"name":"Megan Othus","orcid":"0000-0001-8176-6371","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T02:01:29.001453Z","pmid":"39565908","pmcid":"PMC11972677","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":[]}