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Title:           The Effect of Staging Intervals on Progression-Free Survival in Registration Studies of Oncologic Drugs: A Meta-Analysis
Subject:         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.
Keywords:        meta-analysis; oncologic drug; registration trial; staging
Author:          Jonas A. Zuellig, Roman Adam, Filomena Udry, Ariadna Tibau, Bostjan Šeruga, Alberto Ocaña, Eitan Amir and Arnoud J. Templeton
Creator:         LaTeX with hyperref
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     Item: 
      Title: Introduction 
      Destination: section.1
     Item: 
      Title: Materials and Methods 
      Destination: section.2
      Children: 
       Item: 
        Title: Data Sources and Searches 
        Destination: subsection.2.1
       Item: 
        Title: Study Selection 
        Destination: subsection.2.2
       Item: 
        Title: Data Extraction 
        Destination: subsection.2.3
       Item: 
        Title: Data Synthesis 
        Destination: subsection.2.4
       Item: 
        Title: Statistical Analyses 
        Destination: subsection.2.5
     Item: 
      Title: Results 
      Destination: section.3
      Children: 
       Item: 
        Title: Included Studies 
        Destination: subsection.3.1
       Item: 
        Title: Staging Intervals 
        Destination: subsection.3.2
       Item: 
        Title: Subgroup Analyses 
        Destination: subsection.3.3
       Item: 
        Title: Sensitivity Analyses 
        Destination: subsection.3.4
       Item: 
        Title: Meta-Regression 
        Destination: subsection.3.5
     Item: 
      Title: Discussion 
      Destination: section.4
     Item: 
      Title: Conclusions 
      Destination: section.5
     Item: 
      Title: References
      Destination: appendix.A.
   Info: 
    Title: The Effect of Staging Intervals on Progression-Free Survival in Registration Studies of Oncologic Drugs: A Meta-Analysis
    Author: Jonas A. Zuellig, Roman Adam, Filomena Udry, Ariadna Tibau, Bostjan Šeruga, Alberto Ocaña, Eitan Amir and Arnoud J. Templeton
    Subject: 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.
    Keywords: meta-analysis; oncologic drug; registration trial; staging
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