title: Timing and extent of response in colorectal cancer: critical review of current data and implication for future trials.
abstract: The identification of new surrogate endpoints for advanced colorectal cancer is becoming crucial and, along with drug development, it represents a research field increasingly studied. Although overall survival (OS) remains the strongest trial endpoint available, it requires larger sample size and longer periods of time for an event to happen. Surrogate endpoints such as progression free survival (PFS) or response rate (RR) may overcome these issues but, as such, they need to be prospectively validated before replacing the real endpoints; moreover, they often bear many other limitations. In this narrative review we initially discuss the role of time-to-event endpoints, objective response and response rate as surrogates of OS in the advanced colorectal cancer setting, discussing also how such measures are influenced by the tumor assessment criteria currently employed. We then report recent data published about early tumor shrinkage and deepness of response, which have recently emerged as novel potential endpoint surrogates, discussing their strengths and weaknesses and providing a critical comment. Despite being very compelling, the role of such novel response measures is yet to be confirmed and their surrogacy with OS still needs to be further investigated within larger and well-designed trials.
authors: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors: Giuseppe
authors: G
authors: Aprile
authors: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors: Caterina
authors: C
authors: Fontanella
authors: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors: Marta
authors: M
authors: Bonotto
authors: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors: Karim
authors: K
authors: Rihawi
authors: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors: Stefania Eufemia
authors: SE
authors: Lutrino
authors: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors: Laura
authors: L
authors: Ferrari
authors: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors: Mariaelena
authors: M
authors: Casagrande
authors: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors: Elena
authors: E
authors: Ongaro
authors: Department of Medical Oncology, National Cancer Institute, Aviano, Italy.
authors: Massimiliano
authors: M
authors: Berretta
authors: Gastrointestinal Medical Oncology Unit, National Cancer Institute, Napoli, Italy.
authors: Antonio
authors: A
authors: Avallone
authors: Medical Oncology Unit, San Carlo Hospital, Potenza, Italy.
authors: Gerardo
authors: G
authors: Rosati
authors: Department of Medical Oncology, National Cancer Institute, Bari, Italy.
authors: Francesco
authors: F
authors: Giuliani
authors: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors: Gianpiero
authors: G
authors: Fasola
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018450:Disease Progression; D018572:Disease-Free Survival; D023381:Endpoint Determination; D019317:Evidence-Based Medicine; D006801:Humans; D012107:Research Design; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
keywords: colorectal cancer; deepness of response; early tumor shrinkage; endpoint; response rate