Clinical Benefit Response in Pancreatic Cancer Trials Revisited

Abstract

Objectives: Clinical benefit response (CBR), based on changes in pain, Karnofsky performance status, and weight, is an established palliative endpoint in trials for advanced gastrointestinal cancer. We investigated whether CBR is associated with survival, and whether CBR reflects a wide-enough range of domains to adequately capture patients' perception. Methods: CBR was prospectively evaluated in an international phase III chemotherapy trial in patients with advanced pancreatic cancer (n = 311) in parallel with patient-reported outcomes (PROs). Results: The median time to treatment failure was 3.4 months (range: 0-6). The majority of the CBRs (n = 39) were noted in patients who received chemotherapy for at least 5 months. Patients with CBR (n = 62) had longer survival than non-responders (n = 182) (hazard ratio = 0.69; 95% confidence interval: 0.51-0.94; p = 0.013). CBR was predicted with a sensitivity and specificity of 77-80% by various combinations of 3 mainly physical PROs. A comparison between the duration of CBR (n = 62, median = 8 months, range = 4-31) and clinically meaningful improvements in the PROs (n = 100-116; medians = 9-11 months, range = 4-24) showed similar intervals. Conclusion: CBR is associated with survival and mainly reflects physical domains. Within phase III chemotherapy trials for advanced gastrointestinal cancer, CBR can be replaced by a PRO evaluation, without losing substantial information but gaining complementary information.

Patients with Advanced Disease: The Value of Patient Reported Outcomes

“…Notably, the present work of Bernhard et al [1] was supported by both public and private funding. This may reflect the fact that also physician-researchers and pharmaceutical companies are increasingly interested in this topic [5].…”

“…Survival data and other findings of the RCT have been reported earlier [1,3]. Jürg Bernhard and his co-authors emphasize the value of measuring PRO and Qol of the patients to assess the actual benefit that patients may expect from disease modifying interventions in this incurable and life-limiting phase of the disease.…”

“…In this issue of ONCOLOGY RESEARCH AND TREATMENT , Jürg Bernhard and colleagues [1] present quality of life (Qol) data, findings from other patient reported outcome measures (PRO) and performance status assessments from a randomized controlled trial (RCT) of patients with advanced pancreatic cancer (median survival of their patients was 7-8 months). Survival data and other findings of the RCT have been reported earlier [1,3].…”

“…Jürg Bernhard and his co-authors emphasize the value of measuring PRO and Qol of the patients to assess the actual benefit that patients may expect from disease modifying interventions in this incurable and life-limiting phase of the disease. They argue that in contrast to ‘tumor centered outcomes' [1] such PRO and Qol measures are essential for a patient centered assessment of treatments' effect on patients' survival and wellbeing. In their study they specifically assessed whether ‘clinical benefit response' (CBR), a combined measure of performance status, pain intensity, and body weight is associated with survival, and whether CBR reflects a wide-enough range of domains to adequately capture patients' perception.…”

“…Even if Qol and other PRO are obtained in clinical trials, reporting and appraisal of these findings is frequently insufficient [8,9]. Paradoxically, the publication process of the randomized controlled trial SAKK 44/00-CECOG/PAN.1.3.001 [3] that provided the data base for the study presented by Bernhard et al [1] is a classic example. Although Qol and PRO data were obtained in the trial, authors of the primary publication did not report these findings [3].…”