{"doi":"10.1016/j.esmoop.2025.105808","title":"Cyclin-dependent kinase 4/6 inhibitors beyond progression in hormone receptor-positive, HER2-negative advanced breast cancer: a systematic review and meta-analysis (REIGNITE study)","abstract":"BACKGROUND: Adding cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) to endocrine therapy (ET) is considered the first-line treatment of advanced HR-positive/HER2-negative breast cancer. However, with the recent approval of several additional targeted agents, the optimal treatment sequencing remains uncertain, and it is unclear whether the benefits of CDK4/6i extend beyond progression on first-line therapy. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis to evaluate the efficacy of CDK4/6i in the second-line setting after progression on CDK4/6i in the first line, with a particular focus on patients who had either PIK3CA or ESR1 mutation. We included randomized clinical trials (RCTs) comparing CDK4/6i combined with ET to ET alone in patients who experienced tumor progression on CDK4/6i treatment in the first-line setting. The results were pooled using a random-effects model with 95% confidence interval (CI). RESULTS: Five RCTs encompassing 1184 patients were included. Overall, CDK4/6i plus ET significantly improved progression-free survival (PFS) versus ET alone, yielding a hazard ratio of 0.73 (95% CI 0.56-0.94, P < 0.05), with a more prominent benefit in patients who switched the CDK4/6i (hazard ratio 0.61, 95% CI 0.48-0.77, P < 0.05). The benefit was consistent in patients with somatic PIK3CA mutations (hazard ratio 0.71, 95% CI 0.52-0.98, P < 0.05), and ESR1 mutations (hazard ratio 0.66, 95% CI 0.49-0.89, P < 0.05). The toxicity profile was compatible with the known side effects from CDK4/6i. CONCLUSIONS: Our results support the strategy of switching the CDK4/6i in the second-line setting and demonstrate persistent benefit even in patients with PIK3CA or ESR1 mutations.","journal":"ESMO Open","year":2025,"id":520172,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9618,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1389197,"name":"Luís Felipe Leite","orcid":"0009-0006-8347-1212","position":1,"is_corresponding":false},{"id":1389198,"name":"Valbert Oliveira Costa Filho","orcid":"0009-0003-2864-0966","position":2,"is_corresponding":false},{"id":1389199,"name":"Mariana Macambira Noronha","orcid":"0000-0003-0889-7425","position":3,"is_corresponding":false},{"id":1389200,"name":"Anelise Poluboiarinov Cappellaro","orcid":"0009-0001-1624-7556","position":4,"is_corresponding":false},{"id":521050,"name":"Maria João Gouveia","orcid":"0000-0003-3747-5520","position":5,"is_corresponding":false},{"id":1389739,"name":"J L da Silva","orcid":null,"position":6,"is_corresponding":false},{"id":808058,"name":"Brenda Ernst","orcid":"0000-0002-7292-3950","position":7,"is_corresponding":false},{"id":679967,"name":"Andréia Cristina de Melo","orcid":"0000-0002-1201-4333","position":8,"is_corresponding":false},{"id":1075902,"name":"Paolo Tarantino","orcid":"0000-0001-8686-0228","position":9,"is_corresponding":false},{"id":858033,"name":"Felipe Batalini","orcid":"0000-0003-3354-308X","position":10,"is_corresponding":false},{"id":1389196,"name":"Luiz F. Costa de Almeida","orcid":"0009-0008-3286-3333","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:49:23.618703Z","pmid":"41037898","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":[]}