{"doi":"10.3233/kca-240016","title":"Effectiveness of Second-Line Cabozantinib in Metastatic Clear Cell Renal Cell Carcinoma Patients After First-Line Treatment with Immune Checkpoint Inhibitor-based Combinations","abstract":"Background: Cabozantinib, a tyrosine kinase inhibitor (TKI), is a prevalent second-line (2 L) therapy and was approved for use after progression on TKIs. However, the 1 L treatment setting has changed since the approval of cabozantinib monotherapy in salvage therapy settings. Objective: To assess the differential effectiveness of cabozantinib after prior progression on 1 L ipilimumab with nivolumab (IPI + NIVO) compared to programmed death receptor-1 (PD-1) or PD-1 ligand (PD-L1) inhibitors (PD1/L1i) with TKIs. Methods: Utilizing a nationwide electronic health record (EHR)-derived de-identified database, we included patients with metastatic clear cell renal cell carcinoma (mccRCC) who received 1 L treatment with an immune checkpoint inhibitor (ICI)-based combination and 2 L treatment with cabozantinib monotherapy. These patients were categorized based on the type of 1 L ICI-based combination received: IPI + NIVO vs. PD1/L1i with TKI. Real-world time to next therapy (rwTTNT) and real-world overall survival (rwOS) were summarized using Kaplan-Meier curves and compared using Cox-proportional hazard models adjusted for International mRCC Database Consortium (IMDC) risk groups. Results: Among 12,285 patients with metastatic renal cell carcinoma, 237 were eligible and included. Median rwTTNT was 8 months for the IPI + NIVO subgroup and 7.5 months for the PD1/L1i + TKI subgroup (HR 1.05, 95% CI: 0.74–1.49, p = 0.8). Median rwOS was 17 months for IPI + NIVO and 16 months for PD1/L1i + TKI subgroup (HR 0.79, 95% CI: 0.52–1.20, p = 0.3). Conclusions: Cabozantinib remains effective as a 2 L therapy for mccRCC independent of the type of prior 1 L ICI-based combination. Further research is needed to validate these findings and explore the ideal sequencing of therapies.","journal":"Kidney Cancer","year":2024,"id":460042,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"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":1097702,"name":"Georges Gebrael","orcid":"0000-0002-4085-6415","position":1,"is_corresponding":false},{"id":862291,"name":"Yeonjung Jo","orcid":"0000-0002-1630-2957","position":2,"is_corresponding":false},{"id":1097703,"name":"Vinay Mathew Thomas","orcid":"0000-0001-9916-730X","position":3,"is_corresponding":false},{"id":1287538,"name":"Haoran Li","orcid":"0000-0002-7046-9379","position":4,"is_corresponding":false},{"id":1097701,"name":"Gliceida Galarza Fortuna","orcid":"0000-0002-1084-953X","position":5,"is_corresponding":false},{"id":663744,"name":"Nicolas Sayegh","orcid":"0000-0003-1924-8148","position":6,"is_corresponding":false},{"id":1288078,"name":"Clara Tandar","orcid":null,"position":7,"is_corresponding":false},{"id":663746,"name":"Nishita Tripathi","orcid":"0000-0003-2161-1567","position":8,"is_corresponding":false},{"id":1287539,"name":"Beverly Chigarira","orcid":"0009-0001-6253-2374","position":9,"is_corresponding":false},{"id":1287540,"name":"Ayana Srivastava","orcid":"0009-0002-9521-5436","position":10,"is_corresponding":false},{"id":1287541,"name":"Chadi Hage Chehade","orcid":"0009-0008-6735-5777","position":11,"is_corresponding":false},{"id":1287542,"name":"Blake Nordblad","orcid":"0000-0002-7104-1358","position":12,"is_corresponding":false},{"id":298937,"name":"Benjamin L. Maughan","orcid":"0000-0002-0010-8551","position":13,"is_corresponding":false},{"id":105193,"name":"Neeraj Agarwal","orcid":"0000-0003-1076-0428","position":14,"is_corresponding":false},{"id":298929,"name":"Umang Swami","orcid":"0000-0003-3518-0411","position":15,"is_corresponding":false},{"id":1287537,"name":"Arshit Narang","orcid":"0009-0003-0993-1805","position":0,"is_corresponding":true}],"reference_count":24,"raw_metadata":null,"created_at":"2026-07-19T02:04:03.568045Z","pmid":"39263256","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":[]}