Biomarker Enrichment Strategies: Matching Trial Design to Biomarker Credentials

Overview

Journal Nat Rev Clin Oncol

Specialty Oncology

Date 2013 Nov 28

PMID 24281059

Citations 72

Authors

Boris Freidlin

Edward L Korn

Affiliations

Soon will be listed here.

Abstract

The use of biomarkers to identify patients who can benefit from treatment with a specific anticancer agent has the potential to both improve patient care and accelerate drug development. The development of targeted agents and their accompanying biomarkers frequently occurs contemporaneously, and confidence in a putative biomarker's performance might, therefore, be insufficient to restrict the definitive testing of a new agent to the subgroup of biomarker-positive patients. This Review considers which clinical trial designs and analysis strategies are appropriate for use in phase III, biomarker-driven, randomized clinical trials, on the basis of pre-existing evidence that the biomarker can successfully identify patients who will respond to the treatment in question. The types of interim monitoring that are appropriate for these trials are also discussed. In addition, enrichment strategies based on the use of prognostic biomarkers to separate a population into subgroups with better and worse outcomes, regardless of treatment, are described. Finally, the possibility of formally using a biomarker during phase II drug development, to select what type of biomarker-driven strategy should be used in the phase III trial, is discussed.

Citing Articles

Association of maternal blood metabolomics and gestational diabetes mellitus risk: a systematic review and meta-analysis.

Zhou J, Yu J, Ren J, Ren Y, Zeng Y, Wu Y Rev Endocr Metab Disord. 2024; .

PMID: 39602052 DOI: 10.1007/s11154-024-09934-5.

Exploring the clinical implications and applications of exosomal miRNAs in gliomas: a comprehensive study.

Yang L, Niu Z, Ma Z, Wu X, Vong C, Li G Cancer Cell Int. 2024; 24(1):323.

PMID: 39334350 PMC: 11437892. DOI: 10.1186/s12935-024-03507-x.

Artificial intelligence in oncology: ensuring safe and effective integration of language models in clinical practice.

Verlingue L, Boyer C, Olgiati L, Brutti Mairesse C, Morel D, Blay J Lancet Reg Health Eur. 2024; 46:101064.

PMID: 39290808 PMC: 11406067. DOI: 10.1016/j.lanepe.2024.101064.

The potential of miRNA-based approaches in glioblastoma: An update in current advances and future perspectives.

Ordonez-Rubiano E, Rincon-Arias N, Espinosa S, Shelton W, Salazar A, Combita A Curr Res Pharmacol Drug Discov. 2024; 7:100193.

PMID: 39055532 PMC: 11268206. DOI: 10.1016/j.crphar.2024.100193.

Efficient testing of the biomarker positive and negative subgroups in a biomarker-stratified trial.

Li L, Ivanova A Biometrics. 2024; 80(2).

PMID: 38861372 PMC: 11166030. DOI: 10.1093/biomtc/ujae056.

References

Jimeno A, Messersmith W, Hirsch F, Franklin W, Eckhardt S . KRAS mutations and sensitivity to epidermal growth factor receptor inhibitors in colorectal cancer: practical application of patient selection. J Clin Oncol. 2009; 27(7):1130-6. DOI: 10.1200/JCO.2008.19.8168. View

Freidlin B, McShane L, Korn E . Randomized clinical trials with biomarkers: design issues. J Natl Cancer Inst. 2010; 102(3):152-60. PMC: 2911042. DOI: 10.1093/jnci/djp477. View

Herbst R, Sun Y, Eberhardt W, Germonpre P, Saijo N, Zhou C . Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol. 2010; 11(7):619-26. PMC: 3225192. DOI: 10.1016/S1470-2045(10)70132-7. View

Temple R . Enrichment of clinical study populations. Clin Pharmacol Ther. 2010; 88(6):774-8. DOI: 10.1038/clpt.2010.233. View

Sparano J . TAILORx: trial assigning individualized options for treatment (Rx). Clin Breast Cancer. 2006; 7(4):347-50. DOI: 10.3816/CBC.2006.n.051. View

Spigel D, Edelman M, Mok T, OByrne K, Paz-Ares L, Yu W . Treatment Rationale Study Design for the MetLung Trial: A Randomized, Double-Blind Phase III Study of Onartuzumab (MetMAb) in Combination With Erlotinib Versus Erlotinib Alone in Patients Who Have Received Standard Chemotherapy for Stage IIIB or IV.... Clin Lung Cancer. 2012; 13(6):500-4. DOI: 10.1016/j.cllc.2012.05.009. View

Van Cutsem E, Kohne C, Lang I, Folprecht G, Nowacki M, Cascinu S . Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011; 29(15):2011-9. DOI: 10.1200/JCO.2010.33.5091. View

Van Cutsem E, Kohne C, Hitre E, Zaluski J, Chang Chien C, Makhson A . Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009; 360(14):1408-17. DOI: 10.1056/NEJMoa0805019. View

Freidlin B, McShane L, Polley M, Korn E . Randomized phase II trial designs with biomarkers. J Clin Oncol. 2012; 30(26):3304-9. PMC: 3434989. DOI: 10.1200/JCO.2012.43.3946. View

10.

Karuri S, Simon R . A two-stage Bayesian design for co-development of new drugs and companion diagnostics. Stat Med. 2012; 31(10):901-14. DOI: 10.1002/sim.4462. View

11.

Jiang W, Freidlin B, Simon R . Biomarker-adaptive threshold design: a procedure for evaluating treatment with possible biomarker-defined subset effect. J Natl Cancer Inst. 2007; 99(13):1036-43. DOI: 10.1093/jnci/djm022. View

12.

Romond E, Perez E, Bryant J, Suman V, Geyer Jr C, Davidson N . Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005; 353(16):1673-84. DOI: 10.1056/NEJMoa052122. View

13.

Scagliotti G, Vynnychenko I, Park K, Ichinose Y, Kubota K, Blackhall F . International, randomized, placebo-controlled, double-blind phase III study of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous non-small-cell lung cancer: MONET1. J Clin Oncol. 2012; 30(23):2829-36. DOI: 10.1200/JCO.2011.41.4987. View

14.

Rubinstein L, Korn E, Freidlin B, Hunsberger S, Ivy S, Smith M . Design issues of randomized phase II trials and a proposal for phase II screening trials. J Clin Oncol. 2005; 23(28):7199-206. DOI: 10.1200/JCO.2005.01.149. View

15.

Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M . A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004; 351(27):2817-26. DOI: 10.1056/NEJMoa041588. View

16.

McShane L, Cavenagh M, Lively T, Eberhard D, Bigbee W, Williams P . Criteria for the use of omics-based predictors in clinical trials: explanation and elaboration. BMC Med. 2013; 11:220. PMC: 3852338. DOI: 10.1186/1741-7015-11-220. View

17.

Peeters M, Price T, Cervantes A, Sobrero A, Ducreux M, Hotko Y . Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010; 28(31):4706-13. DOI: 10.1200/JCO.2009.27.6055. View

18.

Freidlin B, Korn E, Gray R . Marker Sequential Test (MaST) design. Clin Trials. 2013; 11(1):19-27. PMC: 11406163. DOI: 10.1177/1740774513503739. View

19.

Simon R . The use of genomics in clinical trial design. Clin Cancer Res. 2008; 14(19):5984-93. DOI: 10.1158/1078-0432.CCR-07-4531. View

20.

Redman M, Crowley J, Herbst R, Hirsch F, Gandara D . Design of a phase III clinical trial with prospective biomarker validation: SWOG S0819. Clin Cancer Res. 2012; 18(15):4004-12. PMC: 3409929. DOI: 10.1158/1078-0432.CCR-12-0167. View