Response Rates, Survival, and Chemotherapy Trials

Extract

Early clinical trials of a novel oncology agent or combination regimen usually examine the biologic activity of the therapy using surrogate end points. These end points are believed to predict the clinical benefit of the new treatment, which is then tested in subsequent controlled, randomized clinical trials. The most commonly used surrogate end point, the response rate, has conventionally been examined in phase II trials and allows the early determination of the antitumor activity of the new therapy.

Response rate determinations reflect tumors that exhibit a complete regression or show a defined reduction for a specified time period. Stable tumors are excluded from response rate determinations. Accurate response rate determinations can be confounded by subjective biases introduced in unblinded clinical trials and inaccuracies of radiographic techniques and measurements.

Clinical benefit, a regulatory end point used in traditional drug approval, has generally been characterized by an increase in patient survival, an unambiguous gold standard of efficacy, or by relieving or delaying the onset of disease-related symptoms. The demonstration of improving survival may be obscured by subsequent therapies after disease progression in randomized trials. Relief of tumor-related symptoms has been difficult to document in oncology trials because of traditionally restrictive eligibility criteria that allow only asymptomatic or early symptomatic patients into the trials.