Assessing oncologic benefit in clinical trials of immunotherapy agents.
BACKGROUND
USA Food and Drug Administration approval for cancer therapy requires demonstration of patient benefit as a marker of clinical efficacy. Prolonged survival is the gold standard for demonstration of efficacy, but other end points such as antitumor response, progression-free survival, quality of life, or surrogate end points may be used.


METHODS
This study was developed based on discussion during a roundtable meeting of experts in the field of immunotherapy.


RESULTS
In most clinical trials involving cytotoxic agents, response end points use RECIST based on the premise that 'effective' therapy causes tumor destruction, target lesion shrinkage, and prevention of new lesions. However, RECIST may not be appropriate in trials of immunotherapy. Like other targeted agents, immunotherapies may mediate cytostatic rather than direct cytotoxic effects, and these may be difficult to quantify with RECIST. Furthermore, significant time may elapse before clinical effects are quantifiable because of complex response pathways. Effective immunotherapy may even mediate transient lesion growth secondary to immune cell infiltration.


CONCLUSIONS
RECIST may not be an optimal indicator of clinical benefit in immunotherapy trials. This article discusses alternative clinical trial designs and end points that may be more relevant for immunotherapy trials and may offer more effective prediction of survival in pivotal phase III studies.
Hales
R K
RK
Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD.
Banchereau
J
J
Baylor Institute for Immunology Research, Dallas, TX.
Ribas
A
A
Division of Hematology-Oncology, University of California Los Angeles, Los Angeles, LA.
Tarhini
A A
AA
Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA.
Weber
J S
JS
Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
Fox
B A
BA
Earle A. Chiles Research Institute, Providence Cancer Center and Oregon Health and Science University, Portland, ME, USA.
Drake
C G
CG
Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address: cdrake@jhmi.edu.
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000628:therapy*
D000970:Antineoplastic Agents