In the phase II CUPISCO trial reported in The Lancet, Krämer et al found that molecularly guided therapy in patients with unfavorable nonsquamous cancer of unknown primary who had disease control on first-line platinum-based therapy resulted in better progression-free survival vs patients who continued chemotherapy.
Study Details
In the international open-label trial, 436 patients with disease control after three cycles of platinum-based chemotherapy were randomly assigned 3:1 between July 2018 and December 2022 to molecularly guided therapy (n = 326) or at least three additional cycles of platinum-based chemotherapy (n = 110). Molecularly guided therapy was selected on the basis of comprehensive genomic profiling, which was performed in all study patients. Patients in the molecularly guided therapy group with an actionable molecular profile received targeted therapy or atezolizumab monotherapy; those without an actionable molecular profile received atezolizumab plus continued chemotherapy.
The primary endpoint of the trial was investigator-assessed progression-free survival.
Key Findings
Median follow-up was 24.1 months (interquartile range = 11.6–35.6 months). Median progression-free survival was 6.1 months (95% confidence interval [CI] = 4.7–6.5 months) in the molecularly guided therapy group vs 4.4 months (95% CI = 4.1–5.6 months) in the chemotherapy group (hazard ratio [HR] = 0.72, 95% CI = 0.56–0.92, P = .0079).
In subgroup analyses, median progression-free survival among patients with an actionable molecular profile was 8.1 months (95% CI = 4.6–8.7 months) in the molecularly guided therapy group vs 4.7 months (95% CI = 4.0–6.6 months) in the chemotherapy group (HR = 0.65, 95% CI = 0.42–0.99). Among patients without an actionable molecular profile, median progression-free survival was 5.5 months (95% CI = 4.5–6.4 months) in the molecularly guided therapy group vs 4.4 months (95% CI = 4.2–5.6 months) in the chemotherapy group (HR = 0.76, 95% CI = 0.54–1.06).
At interim analysis, median overall survival was 14.7 months (95% CI = 13.3–17.3 months) in the molecularly guided therapy group vs 11.0 months (95% CI = 9.7–15.4 months) in the chemotherapy group.
As stated by the investigators, “Related adverse event rates per 100-patient-years at risk were generally similar or lower with molecularly guided therapy vs chemotherapy.”
The authors concluded, “In patients with previously untreated, unfavorable, nonsquamous cancer of unknown primary who reached disease control after induction chemotherapy, comprehensive genomic profiling with subsequent molecularly guided therapies resulted in longer progression-free survival than standard platinum-based chemotherapy. On the basis of these results, we recommend that comprehensive genomic profiling is performed at initial diagnosis in patients with unfavorable cancer of unknown primary.”
Alwin Krämer, MD, of the Clinical Cooperation Unit Molecular Hematology-Oncology, German Cancer Research Center, Heidelberg, is the corresponding author for The Lancet article.
Disclosure: The study was funded by F. Hoffmann-La Roche. For full disclosures of the study authors, visit thelancet.com.
