Background: The choice of the activity endpoint is crucial when designing phase II screening trials. This choice is usually guided by convention, but the level of evidence for picking-up one of them is limited.
Methods: We have analysed the phase II trials in carcinoma of unknown primary patients (CUP; 48 strata). We calculated the Pearson correlation coefficient using weighted linear regression to measure the degree of association between the different available activity endpoints (Best objective response - BORR, best tumour control rate - BTCR, 3- and 6-month progression-free rates, 3- and 6-month PFR and median progression-free survival). We also explored the correlation between these endpoints and OS.
Results: All activity endpoints were strongly correlated in CUP studies; all of these endpoints were strongly correlated with OS. The median BORR across the studies was 30%. Positive trials defined by BORR ≥ 30% were associated with statistically longer PFS (4.8 versus 3.7 months, P = 0.013) and OS (10.0 versus 8.0, P = 0.0007).
Discussion: In phase II studies with CUP patients, BORR and the threshold of BORR > 30% for defining promising drug appears adequate.
Keywords: activity endpoint; advanced soft-tissue sarcoma; carcinoma of unknown primary; correlation; phase II trials.