Purpose <p>To assess the use of endpoints in phase 3 randomized controlled trials (RCTs) in metastatic breast cancer (BC).</p> Methods <p>Eligible RCTs were searched for in the WHO International Clinical Trials Registry Platform. The impact of selected variables on the use of the primary endpoints was determined with multivariable logistic regression.</p> Results <p>The study included 267 phase 3 RCTs of systemic treatments, started between 2008 and 2025. The most common primary endpoint was progression-free survival (PFS; <i>n</i> = 228; 85.4%). It was less likely in trials of chemotherapy relative to conjugates (adjusted odds ratio [aOR], 0.10; 95% CI 0.01–0.61; <i>p</i> = 0.01). Among the PFS-based trials with available results (<i>n</i> = 107), median improvement in PFS was 2.8&#xa0;months (interquartile [IQ] range, 1.35–5.75). 185/228 (81.1%) trials with PFS as the primary endpoint utilized overall survival (OS) as a secondary endpoint and 108/228 (47.4%) had quality of life (QoL) as a secondary endpoint. OS was used as the primary endpoint in only 35 trials (13.1%). It was more likely in trials enrolling patients with triple-negative BC (TNBC) relative to HER2+ BC (aOR, 5.54; 95% CI 1.57–21.93; <i>p</i> = 0.01). However, line of treatment did not have any statistically significant impact on the odds of OS (<i>p</i> &gt; 0.05)</p> Conclusion <p>OS as the primary endpoint has been almost completely replaced by PFS. Improvements in PFS are often modest. OS should be used as the primary endpoint more frequently, especially in TNBC and trials of later-line treatments. Moreover more trials should include QoL as a secondary endpoint.</p>