Mismatch between pre-clinical cardio-oncology and clinical oncology research

Background Several new cancer drugs have been developed in the last years. The cardiovascular (CV) safety of most oncological therapies is not assessed in phase 3 randomized controlled trials (RCTs), but it can be promptly studied as treatments become available in clinical practice. Conversely, pre-clinical cardio-oncology research may not easily adapt to the evolving landscape of oncological pharmacotherapy. Methods We systematically searched Pubmed for basic science (i.e., cellular and animal) articles on cancer treatment-related CV toxicity (CTR-CVT) published from 2021 to 2024. In parallel, ClinicalTrials.gov was queried for phase 3 RCTs conducted in patients with solid or hematological tumors during the same period. Cancer therapies were grouped in established classes, and the proportion of studies focusing on different treatment modalities was compared between the two datasets by chi-square test. Results Of 494 pre-clinical articles identified from 2021 to 2024, 75 were excluded being reviews or meta-analyses. Among the remaining 419 articles, 359 (84.7%) focused on anthracyclines (91.1% evaluated doxorubicin), 17 (4.0%) addressed tyrosine kinase inhibitors (TKI), 10 (2.4%) HER2 inhibitors, 9 (2.1%) alkylating agents, and <1% other cancer therapies (Figure, panel A). In contrast, 165 (24.1%) of 414 phase 3 RCTs assessed immune checkpoint inhibitors (ICI), 106 (15.5%) TKI, and 95 (13.9%) alkylating agents (Figure, panel B). Notably, only 9 (1.3%) RCTs tested therapeutic strategies including anthracyclines. The proportion of pre-clinical studies about anthracyclines, TKI, alkylating agents, and ICI was significantly different than the one of RCTs (P <0.0001 for all), while HER2 inhibitors were investigated with similar frequency (P = 0.24). Information about CTR-CVT was provided only for 25 (6.0%) RCTs. Conclusions This analysis highlights a significant mismatch between the object of most pre-clinical cardio-oncology research and the cancer treatments that are currently being evaluated in contemporary RCTs. In particular, compared with current clinical oncology studies, pre-clinical cardio-oncology research disproportionately emphasizes anthracyclines. The disconnect between pre-clinical cardio-oncology and clinical oncology research is magnified by the frequent omission of data about CTR-CVT in the reports of RCTs. Bridging this gap is critical to advance the translational impact of basic cardio-oncology research.