TY - JOUR
T1 - The impact of radiological assessment schedules on progression-free survival in metastatic breast cancer
T2 - A systemic review and meta-analysis
AU - Reuven Dabush, Dor
AU - Shepshelovich, Daniel
AU - Shochat, Tzippy
AU - Tibau, Ariadna
AU - Amir, Eitan
AU - Goldvaser, Hadar
N1 - Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/11
Y1 - 2021/11
N2 - Background: The impact of interval of restaging on the observed magnitude of benefit of progression-free survival (PFS) is undefined. Materials and Methods: Phase 3 randomized controlled trials (RCTs) investigating anti-neoplastic drugs for metastatic breast cancer which reported the restaging interval and hazard ratio (HR) for PFS were included. Data on study design and study population were collected. HRs and 95% confidence intervals for PFS and OS (overall survival) were pooled in a meta-analysis. Studies were categorized according to short (<9 weeks) or long (≥9 weeks) restaging interval. The differences in PFS and OS effect between trials employing short and long restaging intervals were assessed as subgroup analyses. Analyses were repeated for pre-specified subgroups. Results: Eighty-nine studies comprising 95 comparisons and 44,901 patients were included. The magnitude of PFS benefit was larger in trials which employed short compared to long restaging intervals, but this difference did not reach the pre-defined threshold for statistical significance (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 trials (HR = 0.78 vs. 0.92, P = 0.04), trials with drugs replacing standard treatment (HR = 0.86 vs. 1.04, P = 0.02) and studies performed in exclusively human epidermal growth factor receptor 2 (HER2) positive disease (HR = 0.72 vs. 0.90, P = 0.02). The magnitude of OS benefit was similar with short and long restaging intervals. Conclusions: Shorter restaging intervals are associated with a higher magnitude of effect on PFS, but not OS. Awareness of the impact of the restaging interval on quantification of PFS is important for the design and interpretation of RCTs.
AB - Background: The impact of interval of restaging on the observed magnitude of benefit of progression-free survival (PFS) is undefined. Materials and Methods: Phase 3 randomized controlled trials (RCTs) investigating anti-neoplastic drugs for metastatic breast cancer which reported the restaging interval and hazard ratio (HR) for PFS were included. Data on study design and study population were collected. HRs and 95% confidence intervals for PFS and OS (overall survival) were pooled in a meta-analysis. Studies were categorized according to short (<9 weeks) or long (≥9 weeks) restaging interval. The differences in PFS and OS effect between trials employing short and long restaging intervals were assessed as subgroup analyses. Analyses were repeated for pre-specified subgroups. Results: Eighty-nine studies comprising 95 comparisons and 44,901 patients were included. The magnitude of PFS benefit was larger in trials which employed short compared to long restaging intervals, but this difference did not reach the pre-defined threshold for statistical significance (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 trials (HR = 0.78 vs. 0.92, P = 0.04), trials with drugs replacing standard treatment (HR = 0.86 vs. 1.04, P = 0.02) and studies performed in exclusively human epidermal growth factor receptor 2 (HER2) positive disease (HR = 0.72 vs. 0.90, P = 0.02). The magnitude of OS benefit was similar with short and long restaging intervals. Conclusions: Shorter restaging intervals are associated with a higher magnitude of effect on PFS, but not OS. Awareness of the impact of the restaging interval on quantification of PFS is important for the design and interpretation of RCTs.
KW - Breast cancer
KW - Intermediate endpoints
KW - Progression-free survival
KW - Restaging interval
UR - http://www.scopus.com/inward/record.url?scp=85115000679&partnerID=8YFLogxK
U2 - 10.1016/j.ctrv.2021.102293
DO - 10.1016/j.ctrv.2021.102293
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C2 - 34543860
AN - SCOPUS:85115000679
SN - 0305-7372
VL - 100
JO - Cancer Treatment Reviews
JF - Cancer Treatment Reviews
M1 - 102293
ER -