# The Effect of Staging Intervals on Progression-Free Survival in Registration Studies of Oncologic Drugs: A Meta-Analysis

## TL;DR

This study found that how often patients are scanned during cancer drug trials can affect how effective the drug appears, with longer intervals suggesting better results.

## Contribution

The study reveals that staging intervals in oncology trials influence progression-free survival hazard ratios, with implications for drug approval assessments.

## Key findings

- Shorter restaging intervals (<8 weeks) were associated with higher hazard ratios (HRs), suggesting lower treatment effectiveness.
- Longer restaging intervals (≥8 weeks) showed lower HRs, indicating a stronger apparent treatment effect.
- Results varied by cancer type, with melanoma and kidney cancer showing opposite trends in HRs based on staging intervals.

## Abstract

This analysis investigated whether the frequency of radiographic assessments affects the perceived effectiveness of clinical trials for cancer drugs. Progression-free survival (PFS), a term used to define the time a patient lives without disease progression, was used for the analysis. This study analyzed pivotal studies supporting drug approvals in Switzerland from 2010 to 2022. Their findings showed that shorter intervals between scans (less than 8 weeks) were linked to higher hazard ratios (HRs), meaning a lower apparent treatment effect, while longer intervals (8 weeks or more) showed a stronger effect. This puts the concern that frequent scans might exaggerate drug benefits into a new perspective. However, results varied by cancer type, drug type, and also the primary outcome of the studies. This study had limitations, such as relying on published rather than individual patient data. Although these findings suggest that the timing of disease assessments may influence trial outcomes, definitive answers require more research to better understand the potential impact of staging intervals.

Background/Objectives: To study whether shorter restaging intervals are associated with lower hazard ratios (HRs) for progression-free survival (PFS), as suggested in breast cancer. Methods: Studies supporting the registration of oncologic drugs in Switzerland from 2010 to 2022 were analyzed. HRs and 95% confidence intervals (CIs) for PFS were pooled in a meta-analysis using the generic inverse-variance method and a random-effects model in RevMan v5.4. The HRs were stratified by restaging intervals (<median vs. ≥median), both overall and within prespecified subgroups. Results: A total of 112 studies comprising 69,579 patients were included. The median restaging interval was 8 weeks, with a range of 4 to 18 weeks. Longer restaging intervals (≥8 weeks) were associated with lower HRs compared to shorter intervals (<8 weeks), with pooled HRs of 0.48 (95% CI: 0.44–0.52) and 0.58 (95% CI: 0.53–0.63), respectively. The difference between the groups was statistically significant (p = 0.005), with a substantial heterogeneity (Cochran’s Q p < 0.001; I2 = 90%). Subgroup analyses based on treatment type, including immunotherapy, monoclonal antibodies, and tyrosine kinase inhibitors, did not show any statistically significant differences in HRs. Studies of melanoma with shorter staging intervals were associated with lower HRs (0.44 vs. 0.58, p = 0.02), whereas shorter interval studies of kidney cancer had higher HRs (0.67 vs. 0.44, p = 0.01). Sensitivity analyses with other cut-offs and a meta-regression yielded similar results. Conclusions: Studies leading to the authorization of drugs to treat incurable solid tumors applying restaging intervals ≥ 8 weeks were associated with lower HRs for PFS. The potential impact of restaging intervals on the results for PFS warrants further investigation.