The impact of radiological assessment schedules on progression-free survival in metastatic breast cancer: A systemic review and meta-analysis

1086 Background: The impact of the interval of radiological assessment on the magnitude of benefit observed in randomized trials (RCTs) in metastatic breast cancer is undefined. Methods: All RCTs investigating anti-neoplastic drugs for metastatic breast cancer published between 2006 and 2019 were identified. Intervals for restaging were categorized as short ( < 9 weeks) or long (≥9 weeks). Hazard ratios (HRs) and 95% confidence intervals for progression-free survival (PFS) and overall-survival (OS) were pooled in a meta-analysis and compared between trials employing short and long restaging intervals assessed as subgroup analyses. Analyses were repeated for pre-specified subgroups according to disease subtype, drug type, whether experimental therapy was added to or replaced standard treatment and whether HR for PFS was < 1 or ≥1. Results: Eighty-nine studies comprising 95 comparisons and 44,901 patients were included. The magnitude of PFS benefit was non-significantly larger in trials which employed short compared to long restaging intervals (HR 0.79 vs. 0.86, p = 0.15). Short restaging interval was associated with significantly higher magnitude of effect on PFS in pre-specified subgroups including non-first line studies (HR 0.78 vs. 0.92, p = 0.04), studies with drugs replacing standard treatment (HR 0.86 vs. 1.04, p = 0.02) and studies performed exclusively in human epidermal growth factor receptor 2 (HER2) positive disease (HR 0.72 vs. 0.90, p = 0.02). Restaging interval was not associated with OS for all included studies (HR 0.92 vs. 0.93, p = 0.66) or for any of the pre-specified subgroups. Conclusions: Shorter restaging intervals are associated with a higher magnitude of effect of PFS, but not OS. Awareness of the impact of the restaging interval on quantification of intermediate endpoints such as PFS is important for the design and interpretation of RCTs.