Across 789 reviewed Phase III oncology trials, endpoint selection varied systematically by disease context, treatment line, and modality. PFS appeared most often in metastatic, targeted, maintenance, and longer-survival settings, while OS-inclusive designs were more concentrated in aggressive diseases, first-line survival-claim settings, and selected immunotherapy or combination programs.
PFS alone was the most common OS/PFS primary strategy, appearing in 277 of 789 trials (35.1%). OS-only primary designs appeared in 94 trials (11.9%), while combined PFS+OS primary designs appeared in 73 trials (9.3%).
The dataset shows a broad preference for PFS as the lead operational endpoint among OS/PFS-based strategies. OS remains visible, but it is less often used as a standalone primary endpoint than PFS.
In metastatic disease, PFS-inclusive primary designs were common. First-line metastatic trials used PFS-inclusive primary designs in 138 of 228 trials (60.5%), while later-line trials used PFS-inclusive designs in 47 of 88 trials (53.4%). In contrast, adjuvant trials were mostly anchored outside OS/PFS, with 49 of 57 trials (86.0%) using other primary endpoint families.
The treatment-line pattern suggests that metastatic trials are more likely to structure primary evidence around PFS, while curative-intent settings more often move toward DFS, EFS, pCR, or related endpoint families.
OS-inclusive primary designs were most concentrated in aggressive diseases where survival events are clinically central and more likely to occur within pivotal follow-up. Gastric/gastroesophageal/esophageal cancer had 17 of 29 trials (58.6%) with OS-inclusive primary architecture, followed by head and neck cancer at 12 of 23 trials (52.2%) and AML/MDS at 9 of 21 trials (42.9%).
Higher OS-inclusive use appears in tumor types where mortality risk, expected event timing, and the clinical meaning of survival benefit align more directly with pivotal trial readout.
PFS-inclusive primary designs were strongest in longer-survival, maintenance-oriented, and hematologic malignancy settings. CLL/SLL used PFS primary in 22 of 24 trials (91.7%), multiple myeloma used PFS-inclusive designs in 36 of 48 trials (75.0%), and lymphoma used PFS-inclusive designs in 29 of 41 trials (70.7%).
The high PFS concentration in CLL/SLL, myeloma, lymphoma, ovarian/peritoneal cancer, and prostate cancer suggests that longer survival horizons and post-progression treatment complexity may shift primary endpoint architecture toward earlier disease-control readouts.
Combination regimens had the highest PFS-inclusive primary use, with 161 of 301 trials (53.5%). Targeted therapies also leaned toward PFS, with 132 of 327 trials (40.4%). Immunotherapy showed a more balanced split: 21 of 74 trials (28.4%) were PFS-inclusive and the same number were OS-inclusive.
Targeted and combination programs show a stronger PFS orientation, while immunotherapy programs appear more evenly distributed between OS-inclusive and PFS-inclusive primary structures.
Combined PFS+OS designs were concentrated in settings where both disease-control timing and survival interpretation appeared to be part of the primary evidence architecture. First-line metastatic trials used combined PFS+OS in 35 of 228 trials (15.4%). NSCLC used combined PFS+OS in 20 of 111 trials (18.0%), and gastric/gastroesophageal/esophageal cancer used it in 6 of 29 trials (20.7%).
Combined PFS+OS designs appear most often in first-line metastatic and high-stakes tumor settings, particularly NSCLC and upper GI cancers. This suggests these programs often combine an earlier disease-control endpoint with survival-level primary evidence.
The dataset indicates that OS, PFS, and combined OS+PFS are used differently across oncology contexts rather than interchangeably. PFS is more common in metastatic and longer-survival settings, OS-inclusive designs cluster in more aggressive or survival-centered indications, and combined PFS+OS designs appear where early disease-control and survival evidence are both embedded in the primary endpoint structure.
The overall pattern is a differentiated endpoint landscape: PFS leads the largest share of OS/PFS primary strategies, OS-inclusive designs concentrate in more survival-sensitive indications, and combined PFS+OS structures appear where both early disease-control and survival interpretation are reflected in the primary endpoint hierarchy.
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