Multinational randomized phase 2 trial of molecularly guided therapy versus chemotherapy for unfavorable cancer of unknown primary

Patients with unfavorable cancer of unknown primary (CUP) have a poor prognosis with standard platinum-based chemotherapy. The randomized phase 2 CUPISCO trial, at 159 sites in 34 countries, compared comprehensive genomic profiling (CGP) resulting in molecularly guided therapy (MGT) versus standard platinum-based chemotherapy for patients with newly diagnosed unfavorable non-squamous CUP after having reached disease control with three cycles of standard platinum-based induction chemotherapy. The primary endpoint was progression-free survival. The median progression-free survival was 6.1 months with MGT versus 4.4 months with chemotherapy (HR 0.72; p=0.0079). Treatment-related adverse events were generally similar or lower with MGT compared with chemotherapy. The authors conclude that in patientsw with previously untreated, unfacorable, non-squamous CUP who reached disease control after induction chemotherapy, CGP with subsequent MGT resulted in longer progression-free survival than standard platinum-based chemotherapy.