A related study of 85 indications for 59 cancer drugs approved in the US found that, of those granted accelerated approval, 21% showed overall survival benefit, 55% established progression-free survival benefit and 24% had no positive confirmatory post-marketing evidence.
Two related editorials discuss this research. They state that these studies serve as a reminder that the accelerated approval pathway is a permissive process that tolerates nonrandomised trial methods and a variety of outcome measures that bear an uncertain relationship to patient benefit. Even the nomenclature of these surrogate outcomes can be misleading to clinicians and patients. Response rate is not a measure of the rate of tumour regression but a measure of the proportion of patients who show a tumour response. This in turn is usually defined as more than 30% reduction using a scoring system that combines tumour measurements and markers at a particular point in time. Other commonly used surrogates include progression-free survival, time to tumour progression, disease-free survival, and recurrence-free survival. These terms overlap and once again can depend on which tests are performed at what time and how they are interpreted. The most important commonality across these measures is their lack of patient centeredness: the inability to reliably correlate these surrogates with outcomes that patients care about.
Given the unsatisfactory nature of these surrogate outcome measures, it is of the greatest concern that these studies show that most of the drugs given accelerated approval have not been shown to improve overall survival in postmarketing trials. The reliance on surrogate end points has real costs for patients and society. Drugs with unproven effectiveness sell false hope to desperate patients, who are likely paying thousands of dollars out of pocket for them. They conclude that the FDA should add rigor to its accelerated approval pathway so that patients with life-threatening cancers do not take drugs that lack reliable evidence of improvements in overall survival or quality of life.