Clinical Trial Intelligence

Is Overall Survival Still the Primary Endpoint Anchor Across European Phase III Oncology Trials?

Across 789 included European Phase III oncology trials, progression-free survival was the largest primary endpoint anchor, while overall survival remained highly visible but more often as a co-primary or secondary endpoint. The signal is not that OS has disappeared from pivotal oncology design, but that the dominant architecture has shifted toward earlier disease-control readouts backed by survival follow-up.

789
Included oncology trials
34.2%
PFS as primary anchor
24.6%
OS as primary or co-primary
55.0%
OS as secondary only

Primary Endpoint Anchor

PFS was the dominant primary anchor, appearing in 270 of 789 trials (34.2%). OS was primary or co-primary in 194 trials (24.6%), split between OS-only primary designs and OS co-primary designs.

Primary Endpoint Anchor Distribution
PFS primary
34.2%
EFS/DFS family
17.9%
OS co-primary
12.7%
OS primary
11.9%
Response / MRD
4.9%
Other primary
18.4%
Phase III Oncology Endpoint Architecture
Conclusion

OS remains clinically central, but it is not the dominant primary endpoint anchor. The largest primary-endpoint bucket is PFS, which indicates a broad shift toward earlier disease-control readouts in European Phase III oncology trials.

Role of Overall Survival

OS appeared somewhere in the endpoint architecture of 628 of 789 trials (79.6%). However, its most common role was secondary-only, seen in 434 trials (55.0%).

Overall Survival Endpoint Role
OS secondary only
55.0%
OS any primary
24.6%
OS absent
20.4%
Phase III Oncology Endpoint Architecture
Conclusion

The modern pattern is not OS abandonment. It is OS repositioning: survival is usually retained, but more often as a secondary or co-primary endpoint behind a faster disease-control primary.

Year-by-Year Endpoint Pattern

The strongest PFS-led signal came from 2024, where PFS primary endpoints appeared in 206 of 545 trials (37.8%). In 2025 and 2026, OS primary exposure increased to 34.1% and 32.4%, largely through co-primary designs.

OS and PFS Endpoint Roles by Authorization Year
2024
PFS primary
37.8%
OS any primary
20.6%
OS secondary only
58.7%
2025
PFS primary
25.0%
OS any primary
34.1%
OS secondary only
46.6%
2026
PFS primary
29.4%
OS any primary
32.4%
OS secondary only
47.1%
Phase III Oncology Endpoint Architecture
Conclusion

The year pattern suggests a hybridization of pivotal endpoint strategy: PFS remains the most common lead endpoint, while OS gains weight through co-primary structures rather than replacing PFS as the dominant anchor.

OS Behind Non-OS Primary Endpoints

When trials led with non-OS primary endpoints, OS was often preserved as a secondary endpoint. This was especially common in PFS-primary trials, where 231 of 270 trials (85.6%) still tracked OS secondarily.

OS Secondary Use Behind Non-OS Primary Anchors
PFS-primary trials
85.6%
EFS/DFS-family trials
85.1%
Response/MRD trials
66.7%
Phase III Oncology Endpoint Architecture
Conclusion

For many oncology programs, OS now functions as the survival validator behind earlier primary endpoints. This creates a two-speed evidence strategy: earlier PFS or disease-control readout first, survival confirmation later.

Time-to-Event Dominance

Taken together, OS primary/co-primary, PFS primary, and EFS/DFS-family primary endpoints accounted for 605 of 789 trials (76.7%). Response-based endpoints accounted for only 39 trials (4.9%) as the main primary anchor.

Endpoint Architecture at a Glance
Time-to-event
605
76.7% of trials
Response/MRD
39
4.9% of trials
Other primary
145
18.4% of trials
Phase III Oncology Endpoint Architecture
Conclusion

European Phase III oncology trial design is still built around time-to-event evidence. The key change is the hierarchy inside that family: PFS and disease-control endpoints are more common lead anchors than OS-only designs.

Executive Interpretation

Across European Phase III oncology trials, OS is still strategically important but no longer the single dominant primary endpoint anchor. The dominant design logic is now PFS or another disease-control endpoint first, with OS frequently retained as the longer-horizon survival endpoint.

Clinical and regulatory implication

For sponsors, the endpoint strategy question is less whether OS matters and more where OS should sit in the evidence hierarchy. In this dataset, the common architecture is clear: use PFS or related disease-control endpoints to accelerate primary readout, while preserving OS to support confirmatory survival interpretation.