Across 68 colorectal, colon, and rectal cancer Phase III studies authorized in CTIS from 2024–2026, PFS appeared as a primary or co-primary endpoint in 17 trials, while OS appeared as a primary or co-primary endpoint in 6 trials. OS/PFS co-primary designs were uncommon, appearing in only 2 trials, while most non-OS/PFS primary endpoints reflected curative-intent, organ-preservation, response, diagnostic, surgical, or safety-driven study designs.
PFS appeared as the only OS/PFS primary endpoint in 15 of 68 trials (22.1%). OS appeared without PFS as a primary endpoint in 4 of 68 trials (5.9%), and OS plus PFS co-primary designs appeared in 2 of 68 trials (2.9%).
The dataset shows PFS as the practical dominant primary endpoint for interventional advanced-disease colorectal cancer trials, while OS-primary use is more selective and generally appears where survival separation is central enough to justify longer follow-up or where PFS alone may not capture the decisive clinical question.
In 2024, OS/PFS primary use was mainly PFS-only or OS-only. In 2025 and 2026, the dataset included explicit OS + PFS co-primary designs, with one such trial in each year.
The later-year appearance of OS + PFS co-primary designs suggests that some contemporary colorectal Phase III programs are anchoring both disease-control and survival claims at the primary level, but this remains a minority pattern rather than the standard endpoint architecture.
Among the 17 trials using PFS as a primary or co-primary endpoint, the dominant context was advanced-disease drug development: metastatic colorectal cancer, locally advanced unresectable colorectal cancer, KRAS G12C-mutant disease, BRAF/KRAS/NRAS-defined disease, or trials using RECIST-based independent radiology review.
PFS appears to function as the principal disease-control endpoint when the trial question depends on earlier radiographic separation, targeted-therapy effect, or randomized comparison in metastatic or unresectable disease. disease-control endpoint when the trial question depends on earlier radiographic separation, targeted-therapy effect, or randomized OS frequently remains present, but more often as a secondary endpoint than as the primary decision endpoint.
OS appeared as a primary or co-primary endpoint in 6 of 68 trials. Only 4 trials used OS without PFS as the primary OS/PFS endpoint, while 2 trials paired OS directly with PFS as co-primary endpoints.
The low OS-primary share suggests that OS is reserved for a narrower set of colorectal Phase III trials where mortality is the central efficacy claim, while many studies use OS as confirmatory secondary evidence behind PFS, DFS, RFS, response, or organ-preservation endpoints.
Non-OS/PFS primary endpoint architectures covered 47 of 68 trials (69.1%). These included DFS, RFS, TTR/TFS, organ preservation, pathological response, ORR, diagnostic sensitivity/specificity, surgical outcomes, toxicity, functional outcomes, and procedure-related endpoints.
The large non-OS/PFS group reflects the diversity of colorectal Phase III development: localized colon cancer often moves toward DFS/RFS, rectal cancer toward organ preservation or pathological response, and surgical or diagnostic studies toward procedure-specific endpoints rather than survival endpoints.
The colorectal Phase III endpoint landscape is not a simple OS-versus-PFS split. PFS is the most common OS/PFS primary endpoint, OS-primary use is selective, and most trials use endpoint architectures shaped by disease setting, resectability, treatment intent, and whether the question is systemic control, survival, organ preservation, surgery, imaging, or pathological response.