Table 3.
Predictors of Overall Survival Benefit following Progression-Free Survival Benefit
| Trial Factor | Proportion of OS+ Trials out of PFS+ Trials (%)† | p-value† | |
|---|---|---|---|
| All PFS+ Trials | 31/82 (37.8%) | - | |
| Total enrollment, median (IQR) | OS benefit | 553 patients (314 – 766) | p=0.58 |
| No OS benefit | 462 patients (346 – 724) | ||
| Industry funding of trial | Yes | 27/77 (35.1%) | p=0.045 |
| No | 4/5 (80.0%) | ||
| Cooperative group trial | Yes | 3/7 (42.9%) | p=0.77 |
| No | 28/75 (37.3%) | ||
| Disease site | Breast | 7/18 (38.9%) | p=0.76 |
| Gastrointestinal | 4/16 (25.0%) | ||
| Genitourinary | 3/8 (37.5%) | ||
| Thoracic | 8/21 (38.1%) | ||
| Other | 9/19 (47.4%) | ||
| Molecular profile restrictiona | Yes | 8/17 (47.1%) | p=0.38 |
| No | 23/65 (35.4%) | ||
| Systemic therapyb | Targeted therapy | 23/68 (33.8%) | p=0.17 |
| Cytotoxic chemotherapy | 7/13 (53.8%) | ||
| Treatment order | First-line therapy | 17/41 (41.5%) | p=0.49 |
| Second-line or higher therapy | 14/41 (34.1%) | ||
| Single-agent or combinationc | Single-agent | 16/43 (37.2%) | p=0.97 |
| Combination | 14/38 (36.8%) | ||
| PFS assessmentd | Investigator-assessed | 9/29 (31.0%) | p=0.73 |
| Independent review | 13/37 (35.1%) | ||
| Co-primary endpointe | Yes | 7/11 (63.6%) | p=0.058 |
| No | 24/71 (33.8%) | ||
| Crossover after progressionf | Allowed | 16/40 (40.0%) | p=0.30 |
| Not Allowed | 10/35 (28.6%) | ||
| PFS HR, median (IQR)g | OS benefit | 0.58 (0.43 – 0.72) | p=0.70 |
| No OS benefit | 0.60 (0.46 – 0.75) | ||
Proportion of PFS PEP trials with PFS benefit (PEP met) where OS benefit was found on initial or subsequent publication. PFS benefit defined as significant PFS benefit as specified for each trial.
p-value reflects Pearson’s Chi-squared test p-values except total enrollment and PFS HR, for which the Mann-Whitney U-test p-value is provided.
Molecular profile restriction refers to those trials that selected for patients with specific tumor-related mutations. This includes trials selecting for patients with EGFR mutation, ALK fusion, BRAF mutation, and similar.
Systemic therapy interventions were divided into targeted therapies (including monoclonal antibodies, small molecule inhibitors, and similar) and cytotoxic chemotherapy; 1 trial investigated a purely nuclear medicine question and was not included in this analysis.
Studies tested either a single-agent intervention (“Single-agent”) or in combination with other oncotherapeutics (“Combination”); 1 trial investigated a purely nuclear medicine question and was not included in this analysis.
PFS assessment (investigator-assessed versus independent central review) provided for trials with PFS as PEP; 16 trials did not specify independent or investigator-assessed PFS assessment and were not included in this analysis.
Trials which had a co-primary OS and PFS endpoint were designated as PFS primary endpoint trials.
Crossover between study arms following disease progression; 7 trials did not specify crossover and were not included in this analysis.
PFS HR reflects the HR for PFS provided at time of initial trial publication; 1 trial did not specify a HR and was not included in this analysis.
Abbreviations: OS, overall survival; PFS, progression-free survival; %, percentage of trials; IQR, interquartile range; HR, hazard ratio; PEP, primary endpoint.