The Effect of Staging Intervals on Progression-Free Survival in Registration Studies of Oncologic Drugs: A Meta-Analysis
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Data Sources and Searches
2.2. Study Selection
2.3. Data Extraction
2.4. Data Synthesis
2.5. Statistical Analyses
3. Results
3.1. Included Studies
3.2. Staging Intervals
3.3. Subgroup Analyses
3.4. Sensitivity Analyses
3.5. Meta-Regression
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
PFS | Progression-Free-Survival |
OS | Overall Survival |
HR | Hazard Ratio |
CI | Confidence Interval |
References
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Total (n = 112) | Restaging Interval < 8 weeks (n = 51) | Restaging Interval ≥ 8 weeks (n = 61) | |
---|---|---|---|
Sample Size (Median, IQR) | 531 (342–713) | 537 (351–658) | 525 (341–762) |
Primary Outcome | |||
PFS, n (%) | 55 (49%) | 18 (16%) | 37 (3%) |
OS, n (%) | 25 (22%) | 14 (12%) | 11 (10%) |
PFS and OS n (%) | 25 (22%) | 15 (13%) | 10 (9%) |
Others n (%) | 7 (6%) | 4 (3%) | 3 (3%) |
Trial Phase | |||
Phase 3 Trial, n (%) | 105 (93%) | 48 (43%) | 57 (50%) |
Phase 2, n (%) | 6 (5%) | 3 (3%) | 3 (2%) |
Phase 2 and 3 (%) | 1 (1%) | - | 1 (1%) |
Randomized, n (%) | 112 (100%) | 51 (46%) | 61 (54%) |
Blinded, n (%) | 58 (51%) | 17 (15%) | 41 (36%) |
Setting | |||
Firstline, n (%) | 37 (33%) | 22 (20%) | 15 (13%) |
Other, n (%) | 75 (66%) | 29 (25%) | 46 (41%) |
Drug class | |||
Chemotherapy, n (%) | 4 (4%) | 1 (1%) | 3 (3%) |
Endocrine Therapy, n (%) | 9 (8%) | - | 9 (8%) |
Immunotherapy, n (%) | 38 (34%) | 26 (23%) | 12 (11%) |
Small Molecule, n (%) | 50 (44%) | 17 (15%) | 33 (29%) |
Antibody Therapy, n (%) | 10 (9%) | 7 (6%) | 3 (3%) |
Radiotherapeutics, n (%) | 1 (1%) | - | 1 (1%) |
Indication Group | |||
Melanoma, n (%) | 14 (12%) | 8 (7%) | 6 (5%) |
Breast, n (%) | 18 (16%) | 6 (5%) | 12 (11%) |
GI (incl. HCC), n (%) | 13 (12%) | 7 (6%) | 6 (6%) |
Lung, n (%) | 23 (20%) | 15 (13%) | 8 (7%) |
Ovarian, n (%) | 9 (8%) | - | 9 (8%) |
Prostate, n (%) | 10 (9%) | - | 10 (9%) |
Renal, n (%) | 8 (7%) | 6 (5%) | 2 (2%) |
Urothelial, n (%) | 3 (3%) | 1 (1%) | 2 (2%) |
Sarcoma and GIST, n (%) | 5 (4%) | 4 (3%) | 1 (1%) |
Other, n (%) | 9 (8%) | 4 (4%) | 5 (4%) |
Subgroup | PFS HR (CI 95%) Restaging Interval < 8 Weeks | PFS HR (CI 95%) Restaging Interval ≥ 8 Weeks | p Value for the Subgroup Difference | Heterogeneity I2 |
---|---|---|---|---|
All (n = 112) | 0.58 (0.53, 0.63), (n = 51) | 0.48 (0.44, 0.52), (n = 61) | 0.004 | 90% |
Drug Class (n = 98) | ||||
Immunotherapy (n = 38) | 0.70 (0.63, 0.77), (n = 26) | 0.66 (0.57, 0.77), (n = 12) | 0.62 | 83% |
Small Molecules (n = 50) | 0.43 (0.37, 0.50), (n = 17) | 0.45 (0.41, 0.51), (n = 33) | 0.63 | 81% |
Antibodies (n = 10) | 0.55 (0.43, 0.70), (n = 7) | 0.55 (0.43, 0.70), (n = 3) | 1.00 | 88% |
Indication Group (n = 76) | ||||
Breast (n = 18) | 0.50 (0.39, 0.64), (n = 6) | 0.58 (0.52, 0.65), (n = 12) | 0.28 | 74% |
Lung (n = 23) | 0.60 (0.51, 0.69), (n = 15) | 0.59 (0.46, 0.75), (n = 8) | 0.93 | 87% |
GI (incl. HCC) (n = 13) | 0.57 (0.48, 0.68), (n = 7) | 0.53 (0.46, 0.61), (n = 6) | 0.52 | 79% |
Melanoma (n = 14) | 0.46 (0.36, 0.57), (n = 8) | 0.63 (0.55, 0.73), (n = 6) | 0.02 | 81% |
Kidney (n = 8) | 0.67 (0.55, 0.81), (n = 6) | 0.44 (0.34, 0.58), (n = 2) | 0.01 | 89% |
Sarcoma and GIST (n = 5) | 0.40 (0.1, 0.88), (n = 4) | 0.31 (0.24, 0.40), (n = 1) | 0.55 | 95% |
Trial Phase | ||||
Phase 3 (n = 105) | 0.58 (0.52, 0.64), (n = 48) | 0.49 (0.44, 0.53), (n = 57) | 0.01 | 90% |
Phase 2 (n = 7) | 0.57 (0.49, 0.67), (n = 3) | 0.40 (0.21, 0.74), (n = 4) | 0.27 | 81% |
Primary Outcome | ||||
PFS (n = 55) | 0.45 (0.39, 0.51), (n = 18) | 0.45 (0.40, 0.51), (n = 37) | 0.95 | 85% |
OS (n = 25) | 0.72 (0.63, 0.83), (n = 14) | 0.58 (0.50, 0.67), (n = 11) | 0.03 | 90% |
PFS and OS (n = 25) | 0.60 (0.52, 0.70), (n = 15) | 0.52 (0.41, 0.65), (n = 10) | 0.26 | 89% |
Others (n = 7) | 0.71 (0.50, 1.01), (n = 4) | 0.35 (0.27, 0.44), (n = 3) | 0.001 | 95% |
Staging Interval (weeks) | HR for PFS 95% Cl | p for Subgroup Difference | Heterogeneity I2 |
---|---|---|---|
<9 (n = 90) vs. ≥9 (n = 22) | 0.54 (0.50, 0.58) vs. 0.45 (0.38, 0.54) | 0.06 | 90% |
<12 (n = 96) vs. ≥12 (n = 16) | 0.55 (0.52, 0.59) vs. 0.38 (0.32, 0.44) | 0.0001 | 90% |
<8 (n = 48) vs. ≥8 (n = 57) without <6 and >12 | 0.60 (0.55, 0.66) vs. 0.49 (0.45, 0.54) | 0.002 | 89% |
≤6 (n = 51) vs. >6 to <12 (n = 45) vs. ≥12 (n = 16) | 0.58 (0.53, 0.64) vs. 0.52 (0.49, 0.58) vs. 0.38 (0.32, 0.44) | <0.001 | 90% |
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Zuellig, J.A.; Adam, R.; Udry, F.; Tibau, A.; Šeruga, B.; Ocaña, A.; Amir, E.; Templeton, A.J. The Effect of Staging Intervals on Progression-Free Survival in Registration Studies of Oncologic Drugs: A Meta-Analysis. Cancers 2025, 17, 1359. https://doi.org/10.3390/cancers17081359
Zuellig JA, Adam R, Udry F, Tibau A, Šeruga B, Ocaña A, Amir E, Templeton AJ. The Effect of Staging Intervals on Progression-Free Survival in Registration Studies of Oncologic Drugs: A Meta-Analysis. Cancers. 2025; 17():1359. https://doi.org/10.3390/cancers17081359
Chicago/Turabian StyleZuellig, Jonas A., Roman Adam, Filomena Udry, Ariadna Tibau, Bostjan Šeruga, Alberto Ocaña, Eitan Amir, and Arnoud J. Templeton. 2025. "The Effect of Staging Intervals on Progression-Free Survival in Registration Studies of Oncologic Drugs: A Meta-Analysis" Cancers 17, no. : 1359. https://doi.org/10.3390/cancers17081359
APA StyleZuellig, J. A., Adam, R., Udry, F., Tibau, A., Šeruga, B., Ocaña, A., Amir, E., & Templeton, A. J. (2025). The Effect of Staging Intervals on Progression-Free Survival in Registration Studies of Oncologic Drugs: A Meta-Analysis. Cancers, 17(), 1359. https://doi.org/10.3390/cancers17081359