Randomized phase 2 trial of molecularly guided therapy versus continued chemotherapy for unfavorable CUP: update from CUPISCO

The multinational, randomized phase 2 CUPISCO trial demosntrated longer progression-free survival (PFS) with comprehensive genomic profiling (CGP) and subsequent molecularly guided therapies (MGTs) versus standard platinum-based chemotherapy among patients with previously untreated, unfavorable cancer of unknown primary (CUP) who reached disease control after three cycles of induction chemotherapy. Updated results from the trial, with a median follow-up of 37.0 months, have now been published. Eligible patients were randomized 3:1 to MGT (investigator-chosen after discussion in a molecular tumor board; n=326) or three further cycles of chemotherapy (n=110). The primary endpoint was PFS. Updated median PFS was 6.1 months with MGT versus 4.4 months with chemotherapy (HR 0.75; 95% CI 0.59-0.95); median overall survival was 15.2 months versus 12.8 months (0.79; 0.61-1.02). No new safety signals were identified. The authors conclude that these results demonstrate the benefit of CGP with subsequent MGT among patients with unfavorable CUP.