Recent research published in JAMA Internal Medicine suggested that the use of surrogate end points for overall survival (OS), including progression-free survival (PFS) and response rate (RR), can meaningfully reduce drug development time in oncology.1
While these end points are used in practice already, novel surrogate end points in oncology — or a reconsideration of how to measure or draw conclusions from current surrogate end points — may be necessary to speed up the drug-development pipeline.
Previous work suggests that drug development — the time between initiating a phase 1 trial and receiving drug approval — can be up to 15 years.2 Yet as understanding of tumor biology, epidemiology, and genetics improves, drugs and novel treatment strategies will begin to be developed increasingly quickly, necessitating a means for determining whether a drug may be effective.
The authors of the present study note, for example, that use of surrogate end points led to the approval of bevacizumab for metastatic breast cancer, though the drug later failed to show any OS benefits.3 A meta-analysis of 36 clinical trials in oncology found, furthermore, that more than half of the studies showed a weak correlation between surrogate end points and OS.4
If surrogate end points are used, a pivotal question is: which ones are best? And, when could faster drug approval times — a possible outcome of the acceptance of surrogate end points as grounds for FDA approval — cause more harm than good?
“Surrogate end points are intermediate end points, usually a change in a lab parameter or other biomarkers, which are supposed to predict clinical benefits,” said Bishal Gyawali, MD, PhD, a research fellow at Brigham and Women’s Hospital in Boston, Massachusetts, in an e-mail. “Clinical end points directly measure clinical benefits such as how the patient feels (QoL; quality of life) or how long the patient lives (OS), while surrogate endpoints in oncology (like RR or PFS) are something the patient doesn’t know until we subject them to scans and tell them that the tumor size is increasing or decreasing.”
“Unfortunately, in oncology, most of these changes in tumor size don’t seem to be well-correlated with QoL or OS — the clinical benefits that patients truly care about,” Dr Gyawali added.