Across 890 oncology phase III trials, progression-free survival (PFS) is the dominant primary efficacy endpoint family: 351 of 789 endpoint-populated trials used PFS as a primary endpoint (44.5%). Overall survival (OS) is less often primary, appearing in 195 of 789 trials (24.7%), but it is present somewhere in the endpoint strategy in 636 of 789 trials (80.6%). The pattern suggests that phase III oncology designs are still anchored by PFS, while OS, safety, response, and patient-reported outcomes are commonly layered around it.
Among 789 trials with primary endpoint text, PFS appeared as a primary endpoint in 351 trials (44.5%). OS appeared as primary in 195 trials (24.7%), while disease-free, event-free, recurrence-free, or metastasis-free survival endpoints appeared in 156 trials (19.8%). Response or remission endpoints were primary in 109 trials (13.8%).
PFS remains the central confirmatory endpoint currency in phase III oncology, but OS is still a major primary endpoint in roughly one quarter of trials. Response endpoints are present, but are more often part of the supporting endpoint package than the primary basis of phase III evidence.
The share of multi-primary endpoint designs rose from 123 of 545 endpoint-populated trials in 2024 (22.6%) to 59 of 176 in 2025 (33.5%) and 25 of 68 in 2026 (36.8%). Over the same period, OS as a primary endpoint increased from 112 of 545 trials (20.6%) in 2024 to 61 of 176 (34.7%) in 2025 and 22 of 68 (32.4%) in 2026.
| Year | PFS primary | OS primary | Response primary | Multi-primary |
|---|---|---|---|---|
| 2024 | 45.5% | 20.6% | 11.0% | 22.6% |
| 2025 | 39.8% | 34.7% | 18.2% | 33.5% |
| 2026 | 48.5% | 32.4% | 25.0% | 36.8% |
The later cohorts show a broader endpoint architecture: more co-primary designs, more OS capture at the primary level, and a higher use of response-based primary endpoints. That suggests sponsors are packaging efficacy evidence across several clinically meaningful views rather than relying on a single time-to-event endpoint.
Secondary endpoint schedules were dense. OS appeared as a secondary endpoint in 505 of 789 trials (64.0%), safety or tolerability in 515 trials (65.3%), patient-reported outcomes or quality of life in 455 trials (57.7%), response endpoints in 412 trials (52.2%), and PFS in 330 trials (41.8%).
The primary endpoint rarely tells the full story. Most phase III oncology trials combine efficacy endpoints with OS follow-up, safety, quality-of-life, and response measures, creating a broader value package for regulators, clinicians, payers, and patients.
Within the 351 trials using PFS as a primary endpoint, OS appeared somewhere in the endpoint strategy in 312 trials (88.9%) and specifically as a secondary endpoint in 262 trials (74.6%). Patient-reported outcomes or quality-of-life endpoints appeared as secondary endpoints in 222 PFS-primary trials (63.2%). Imaging or central review language appeared in the primary PFS endpoint text in 248 trials (70.7%).
PFS-primary phase III trials are not structurally weak on survival follow-up: almost nine in ten include OS somewhere in the endpoint plan. The frequent use of RECIST, BICR, Lugano, RANO, or related imaging language shows that PFS is usually operationalized through standardized assessment frameworks.
PFS was especially dominant in multiple myeloma, appearing as a primary endpoint in 36 of 45 endpoint-populated trials (80.0%), and in lymphoma / CLL, appearing in 44 of 60 trials (73.3%). OS was more dominant in glioblastoma / glioma, appearing as primary in 11 of 16 trials (68.8%), and gastric / gastroesophageal / esophageal cancer, appearing in 16 of 25 trials (64.0%).
| Disease cluster | PFS primary | OS primary | DFS/EFS/RFS primary | Response primary |
|---|---|---|---|---|
| Multiple myeloma | 80.0% | 4.4% | 2.2% | 35.6% |
| Lymphoma / CLL | 73.3% | 3.3% | 3.3% | 16.7% |
| Gastric / GEJ / esophageal | 40.0% | 64.0% | 12.0% | 12.0% |
| Glioblastoma / glioma | 25.0% | 68.8% | 0.0% | 12.5% |
| Bladder / urothelial | 14.3% | 17.9% | 53.6% | 35.7% |
| Breast cancer | 41.0% | 8.6% | 31.4% | 6.7% |
Endpoint selection reflects disease biology and treatment setting. Hematologic malignancy clusters lean heavily toward PFS and response-style measures, while poor-prognosis solid tumors such as glioblastoma and gastric / GEJ / esophageal cancer show stronger OS orientation.
ADC trials had the highest PFS-primary concentration among large modality groups: 60 of 100 ADC-containing phase III trials used PFS as a primary endpoint (60.0%). Bispecific antibody trials followed at 35 of 65 (53.8%). Small molecule and monoclonal antibody trials were also PFS-heavy, at 311 of 674 (46.1%) and 177 of 377 (46.9%), respectively.
| Modality | Trials | PFS primary | OS primary | Response primary |
|---|---|---|---|---|
| ADC | 100 | 60.0% | 34.0% | 16.0% |
| Bispecific antibody | 65 | 53.8% | 33.8% | 18.5% |
| Monoclonal antibody | 377 | 46.9% | 29.4% | 16.4% |
| Small molecule | 674 | 46.1% | 24.3% | 13.9% |
| Radiopharmaceutical | 45 | 35.6% | 8.9% | 2.2% |
ADC and bispecific antibody trials show a strong PFS-primary pattern, consistent with designs where earlier disease-control signals are used to structure confirmatory evidence while OS and response measures remain important supporting endpoints.
PFS means progression-free survival. OS means overall survival. DFS, EFS, RFS, iDFS, DRFS, DDFS, MFS, and related labels were grouped as disease-free, event-free, recurrence-free, relapse-free, or metastasis-free survival endpoints. ORR means objective response rate. DoR means duration of response. PRO means patient-reported outcome. QoL means quality of life. RECIST, Lugano, RANO, BICR, PET, CT, and MRI references were grouped as imaging or central-review endpoint language.