Across 189 unique European CTIS Phase II and III colorectal cancer trials, safety/adverse event endpoints were the most frequently measured endpoint family, appearing in 147 trials (77.8%). Overall survival followed in 130 trials (68.8%), progression-free survival in 102 trials (54.0%), and objective response in 87 trials (46.0%). Phase II leaned toward safety and response-driven endpoint packages, while Phase III shifted toward survival, disease-free/relapse-free survival, and quality-of-life outcomes.
Safety/adverse events, overall survival, progression-free survival, and objective response form the dominant endpoint core. Together, these four endpoint families appeared in 87 to 147 of the 189 included trials.
The European colorectal CTIS endpoint pattern is not response-only: safety, OS, and PFS dominate the measurable evidence package, while ORR remains common but ranks fourth overall.
Primary endpoints were recorded in 177/189 trials (93.7%), secondary endpoints in 157/189 trials (83.1%), and exploratory/other endpoints in 6/189 trials (3.2%). As primary endpoints, safety/AEs led with 52 trials (27.5%), followed by ORR in 44 (23.3%) and PFS in 38 (20.1%).
| Role | #1 | #2 | #3 |
|---|---|---|---|
| Primary | Safety/AEs 52/189 · 27.5% |
ORR 44/189 · 23.3% |
PFS 38/189 · 20.1% |
| Secondary | Safety/AEs 122/189 · 64.6% |
OS 119/189 · 63.0% |
PFS 80/189 · 42.3% |
| Exploratory / other | Biomarker / ctDNA / MRD 4/189 · 2.1% |
OS 3/189 · 1.6% |
Safety/AEs 3/189 · 1.6% |
Primary endpoints concentrate on early efficacy and tolerability signals, while secondary endpoint packages carry the broader registrational evidence layer: safety, OS, PFS, QoL/PRO, ORR, and DOR.
The Phase II cohort included 128 trials and the Phase III cohort included 68 trials. Phase II most often measured safety/AEs (108/128, 84.4%), OS (89/128, 69.5%), PFS (75/128, 58.6%), and ORR (68/128, 53.1%). Phase III most often measured OS (47/68, 69.1%), safety/AEs (45/68, 66.2%), QoL/PRO (32/68, 47.1%), and PFS (29/68, 42.6%).
| Endpoint | Phase II | Phase III |
|---|---|---|
| Safety / AEs | 84.4% | 66.2% |
| OS | 69.5% | 69.1% |
| PFS | 58.6% | 42.6% |
| ORR / response | 53.1% | 30.9% |
| QoL / PRO | 34.4% | 47.1% |
| DFS / RFS | lower than top 10 | 36.8% |
Phase II colorectal trials retain a response-and-safety signal-finding profile, while Phase III adds stronger patient-centered and long-horizon outcomes: QoL/PRO appears in 32/68 Phase III trials (47.1%) and DFS/RFS in 25/68 (36.8%).
Advanced, metastatic, locally advanced, or unresectable CRC labels appeared in 107/189 trials (56.6%). Molecularly defined CRC appeared in 41/189 trials (21.7%), rectal/rectal adenocarcinoma in 34/189 (18.0%), colon/colon adenocarcinoma in 19/189 (10.1%), and localized/adjuvant CRC in 17/189 (9.0%).
| Subgroup | Most frequent endpoint families |
|---|---|
| Advanced/metastatic/unresectable CRC 107 trials |
Safety/AEs 85/107 (79.4%); OS 82/107 (76.6%); PFS 75/107 (70.1%); ORR 68/107 (63.6%) |
| Molecularly defined CRC 41 trials |
Safety/AEs 34/41 (82.9%); PFS 29/41 (70.7%); OS 28/41 (68.3%); ORR 25/41 (61.0%) |
| Rectal / rectal adenocarcinoma 34 trials |
DFS/RFS 24/34 (70.6%); Safety/AEs 24/34 (70.6%); OS 22/34 (64.7%); pathologic response 21/34 (61.8%) |
| Colon / colon adenocarcinoma 19 trials |
DFS/RFS 18/19 (94.7%); Safety/AEs 15/19 (78.9%); OS 13/19 (68.4%); QoL/PRO 7/19 (36.8%) |
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