Research Spotlight: Molecularly guided therapy versus chemotherapy after disease control in unfavourable cancer of unknown primary (CUPISCO): an open-label, randomised, phase 2 study
Krämer A, Bochtler T, Pauli C, et al. Molecularly guided therapy versus chemotherapy after disease control in unfavorable cancer of unknown primary (CUPISCO): an open-label, randomized, phase 2 study. Lancet. Published online July 31, 2024. https://doi.org/10.1016/S0140-6736(24)00814-6
Background:
Cancer of unknown primary (CUP) is defined as “a heterogeneous group of metastatic malignancies for which a primary origin site cannot be identified, accounting for 2-5% of all malignancies, with 80-85% being of an unfavorable subset.” When treated with a standard platinum-based chemotherapy, those diagnosed with an unfavorable subset CUP have a poor prognosis. Because the cancer’s tumor of origin is unknown, targeted treatment has historically been challenging. As a result, there has been little progress in improving the poor outcomes for patients with CUP.
Study details:
The CUPISCO study compared how using comprehensive genomic profiling (CGP) testing at diagnosis to inform molecularly guided therapy (MGT) could impact progression-free and overall survival in patients with CUP compared to standard platinum-based chemotherapy for these patients.
The global multicenter CUPISCO trial spanned 159 sites in 34 countries and included over 400 patients with CUP that was not amenable to resection and/or radiation with curative intent. During induction therapy, patients received three cycles of standard platinum-based chemotherapy. Patients achieving disease control were randomized 3:1 to targeted therapy informed by CGP versus chemotherapy continuation for at least three further cycles. The median progression-free survival in the patients who received MGT was 6.1 months (95% confidence interval [CI] 4.7–6.5) versus 4.4 months (4.1–5.6) for chemotherapy (hazard ratio [HR] 0.72; 95% CI 0.56–0.92; p=0.0079). The median overall survival was 14.7 months (95% CI 13.3–17.3) versus 11.0 months (9.7–15.4), respectively (HR 0.82; 95% CI 0.62–1.09; p=0.1779), though overall survival data were immature at cutoff.
Why this matters:
As this study shows, molecularly guided therapy “conferred a significant and clinically meaningful improvement in progression-free survival” to patients with unfavorable subset CUP as compared with standard platinum-based chemotherapy.
Based on this, the study’s authors recommend that CGP testing by tissue or liquid biopsies, or both, be performed with the initial diagnostic work-up to inform treatment decisions for patients with newly diagnosed, unfavorable CUP.
View the full publication in The Lancet.