Molecularly guided therapy may improve outcomes in patients with unfavourable cancer of unknown primary compared with standard chemotherapy
1. The use of molecularly guided therapy (MGT) was associated with significantly improved progression-free survival (PFS) compared with standard platinum-based chemotherapy in patients with unfavourable cancer of unknown primary (CUP).
Evidence Rating Level: 1 (Excellent)
Comprehensive genetic profiling (CGP) is a novel approach that allows for detection of distinct genomic alterations, allowing for personalized MGT. CUP represents a heterogeneous group of malignancies which have had little progress in improving outcomes, and within which there is a high level of genomic alterations. The CUPISCO trial was a phase II randomized trial to investigate MGT compared with standard platinum-based chemotherapy in patients with a new diagnosis of unfavourable, nonsquamous CUP. The primary analysis was previously completed with a clinical cutoff in 2023, and analysis with extended follow-up was completed to verify these results. 438 patients between July 2018 and December 2022 from 159 centres in 34 countries with a new diagnosis of non-squamous CUP with no previous systemic therapy exposure reached disease control after induction and were randomized to MGT or standard platinum-based chemotherapy. Median follow-up time was 37.0 months (range, 0.0-67.8 months). The updated median PFS was 6.1 months (95% CI, 4.7-6.5) in the MGT arm compared with 4.4 months (95% CI, 4.2-6.4) in the control arm. Among patients who had actionable molecular profiles, the median PFS was 8.2 months (95% CI, 5.0-9.3) in the MGT arm and 5.5 months (95% CI, 4.0-6.9) in the control arm. Overall, analysis of the extended follow-up of the CUPISCO trial aligned with the primary analysis, demonstrating that the use of CGP and subsequent MGT in patients with new non-squamous CUP was associated with significantly improved PFS compared with standard platinum-based chemotherapy.
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