title: The Development of Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP).
abstract: New systemic therapies have prolonged the lives of men with metastatic castration-resistant prostate cancer (mCRPC). Use of these therapies in the adjuvant setting when the disease may be micrometastatic and potentially more sensitive to therapies may decrease mortality from prostate cancer. However, the conduct of adjuvant prostate cancer clinical trials is hampered by taking longer than a decade to reach the meaningful endpoint of overall survival (OS) and the fact that many men never die from prostate cancer, even if they relapse. A validated intermediate clinical endpoint (ICE) in prostate cancer that is a robust surrogate for OS has yet to be defined. This paper details the plans, process, and progress of the international Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) working group to pool individual patient data from all available clinical trials of radiation or prostatectomy for localized disease and conduct the requisite analyses to determine whether an ICE can be identified. This paper further details the challenges and the a priori statistical analytical plans and strategies to define an ICE for adjuvant prostate cancer clinical trials. In addition, a brief review of the health economic analyses to model the benefits to patients, society and manufacturers is detailed. If successful, the results from this work will provide a robust surrogate for OS that will expedite the design and conduct of future adjuvant therapy trials using new agents that have proven activity in mCRPC. Moreover, it will also define the health economic benefits to patients and societies.
authors.forename: Christopher
authors.initials: C
authors.lastname: Sweeney
authors.forename: Mari
authors.initials: M
authors.lastname: Nakabayashi
authors.forename: Meredith
authors.initials: M
authors.lastname: Regan
authors.forename: Wanling
authors.initials: W
authors.lastname: Xie
authors.forename: Julia
authors.initials: J
authors.lastname: Hayes
authors.forename: Nancy
authors.initials: N
authors.lastname: Keating
authors.forename: Suhui
authors.initials: S
authors.lastname: Li
authors.forename: Tomas
authors.initials: T
authors.lastname: Philipson
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.forename: Philip
authors.initials: P
authors.lastname: Kantoff
authors.forename: A Oliver
authors.initials: AO
authors.lastname: Sartor
authors.forename: Howard
authors.initials: H
authors.lastname: Soule
authors.forename: Brandon
authors.initials: B
authors.lastname: Mahal
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000191:economics / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D017024:Chemotherapy, Adjuvant / Q000191:economics; D003362:Cost-Benefit Analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D023381:Endpoint Determination / Q000379:methods / Q000592:standards / Q000639:trends; D006801:Humans; D008136:Longevity; D008297:Male; D015337:Multicenter Studies as Topic; D009364:Neoplasm Recurrence, Local; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000191:economics* / Q000628:therapy*; D018714:Radiotherapy, Adjuvant / Q000191:economics; D016032:Randomized Controlled Trials as Topic; D013223:Statistics as Topic; D013997:Time Factors; D017211:Treatment Failure; D014481:United States
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen