Across 260 unique European CTIS breast cancer Phase II and Phase III trial records first authorized in 2024–2026, safety/tolerability was the most frequent endpoint family overall, appearing in 199 trials (76.5%). Progression-free survival (PFS) was the most frequent primary endpoint family, appearing as a primary endpoint in 76 trials (29.2%), while overall survival (OS) dominated secondary endpoints, appearing as a secondary endpoint in 174 trials (66.9%).
Safety/tolerability endpoints appeared in 199 of 260 trials (76.5%), followed by OS in 181 trials (69.6%), objective response or tumor response in 154 trials (59.2%), and PFS in 134 trials (51.5%).
The breast cancer Phase II/III endpoint landscape is anchored by safety plus classical oncology efficacy endpoints. OS, ORR, and PFS together form the dominant efficacy cluster, while PRO/QoL endpoints are common enough to be a mainstream endpoint family rather than a niche add-on.
Primary endpoints were listed in 249 of 260 trials (95.8%), secondary endpoints in 235 trials (90.4%), and exploratory or other endpoints in 14 trials (5.4%). PFS led the primary layer with 76 trials (29.2% of all trials), OS led the secondary layer with 174 trials (66.9%), and biomarker/molecular endpoints led exploratory endpoints with 11 of 14 exploratory-endpoint trials (78.6%).
Primary endpoints concentrate on a small group of registration-relevant efficacy and safety measures. Secondary endpoints carry most of the broader clinical value story, especially OS, safety, response, PRO/QoL, DOR, and disease control.
Among 152 Phase II trials, safety/tolerability appeared in 115 (75.7%), objective response in 111 (73.0%), OS in 97 (63.8%), and PFS in 88 (57.9%). Among 105 Phase III trials, OS and safety/tolerability each appeared in 82 trials (78.1%), PRO/QoL in 72 (68.6%), PFS in 43 (41.0%), and disease-/event-free survival in 42 (40.0%).
| Endpoint family | Phase II | Phase III |
|---|---|---|
| Safety / tolerability | 75.7% | 78.1% |
| Overall survival | 63.8% | 78.1% |
| Objective response | 73.0% | 38.1% |
| Progression-free survival | 57.9% | 41.0% |
| PRO / QoL | 39.5% | 68.6% |
| Disease-/event-free survival | 17.1% | 40.0% |
Phase II breast cancer trials retain a response-heavy pattern, with ORR or tumor response in 111 of 152 trials. Phase III trials shift toward confirmatory and patient-centered outcomes, especially OS, safety, PRO/QoL, and disease-/event-free survival.
Advanced or metastatic disease was present in 121 of 260 trials (46.5%) and was strongly associated with PFS, ORR, safety, OS, and DOR. Early/adjuvant/neoadjuvant disease appeared in 46 trials (17.7%) and shifted the endpoint pattern toward disease-/event-free survival in 34 trials (73.9%) and pathologic complete response in 20 trials (43.5%).
| Subgroup | Safety | OS | ORR | PFS | DFS/EFS | pCR |
|---|---|---|---|---|---|---|
| Advanced/metastatic (n=121) | 81.0% | 76.0% | 86.0% | 87.6% | — | — |
| HR+/HER2-negative (n=69) | 84.1% | 79.7% | 66.7% | 58.0% | — | — |
| TNBC (n=51) | 84.3% | 84.3% | 74.5% | 56.9% | — | — |
| HER2-positive (n=41) | 87.8% | 78.0% | 63.4% | 58.5% | — | — |
| Early/adjuvant/neoadjuvant (n=46) | 84.8% | 67.4% | 30.4% | — | 73.9% | 43.5% |
| HER2-low (n=11) | 90.9% | 90.9% | 81.8% | 81.8% | — | — |
Advanced/metastatic trials are dominated by time-to-progression and response endpoints, while early-stage trials depend more on curative-setting endpoints such as DFS/EFS and pCR. TNBC and HER2-positive subgroups show broad use of safety, OS, ORR, and PFS rather than a single endpoint family.
Small molecules appeared in 196 of 260 trials (75.4%), monoclonal antibodies in 81 (31.2%), antibody-drug conjugates (ADCs) in 68 (26.2%), and radiopharmaceuticals in 20 (7.7%). ADC-containing trials had particularly high OS (59 of 68; 86.8%), safety (55 of 68; 80.9%), ORR (52 of 68; 76.5%), and PFS (45 of 68; 66.2%) coverage.
ADC and monoclonal-antibody trials show a broad confirmatory endpoint profile with high OS, safety, ORR, and PFS coverage. Radiopharmaceutical breast cancer trials are distinct: imaging or diagnostic endpoints dominate 18 of 20 trials (90.0%).
The 260 trials contained 2,032 endpoint entries: 378 primary endpoint entries (18.6%), 1,629 secondary endpoint entries (80.2%), and 25 exploratory/other endpoint entries (1.2%). On average, each trial listed 1.45 primary endpoint entries and 6.27 secondary endpoint entries.
The operational endpoint burden is overwhelmingly secondary. Breast cancer trial teams should expect the primary endpoint strategy to be relatively concentrated, while secondary endpoints carry most of the measurement complexity across efficacy, safety, PRO/QoL, pharmacokinetics, biomarkers, and treatment exposure.
By first CTIS authorization year, 181 of 260 trials (69.6%) were authorized in 2024, 59 (22.7%) in 2025, and 20 (7.7%) in 2026. The median interval from initial CTIS/EU submission to first CTIS authorization was 65 days across 260 trials, with an interquartile range of 32 to 111 days.
The endpoint dataset is heavily weighted toward CTIS-authorized 2024 European submissions, but 2025 and 2026 records add newer trial-design signals. The 65-day median submission-to-authorization interval provides a practical EU planning benchmark for breast cancer Phase II/III trial intelligence.
Definitions reflect how endpoint abbreviations were used in the CTIS endpoint text.