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

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 ( = 0.005), with a substantial heterogeneity (Cochran's Q < 0.001; I = 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, = 0.02), whereas shorter interval studies of kidney cancer had higher HRs (0.67 vs. 0.44, = 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.