In a Chinese single-center trial (Fudan CUP-001) reported in The Lancet Oncology, Liu et al found that site-specific therapy guided by a 90-gene expression assay improved progression-free survival vs empirical chemotherapy in previously untreated patients with cancer of unknown primary (CUP) who were not amenable to local radiation therapy.
Study Details
In the trial, 182 patients at Fudan University Shanghai Cancer Center were randomly assigned between September 2017 and March 2021 to receive site-specific therapy based on use of the 90-gene assay (n = 91) or empirical chemotherapy (n = 91). The five most common assay-predicted tissues of origin in the site-specific therapy group were gastroesophagus (15%), lung (13%), ovary (12%), cervix (12%), and breast (10%); if the assay did not predict tissue of origin, patients received empirical therapy (26%). Empirical chemotherapy consisted of a taxane at 175 mg/m² on day 1 plus platinum (cisplatin at 75 mg/m² or carboplatin at area under the curve = 5 on day 1, or gemcitabine at 1,000 mg/m² days 1 and 8 plus platinum at the same dose as already outlined) given every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint of the trial was progression-free survival in the intention-to-treat population.
Key Findings
At data cutoff in April 2023, median follow-up was 33.3 months (interquartile range [IQR] = 30.4–51.0 months) in the site-specific therapy group and 30.9 months (IQR = 27.6–35.5 months) in the empirical chemotherapy group. Median progression-free survival was 9.6 months (95% confidence interval [CI] = 8.4–11.9 months) in the site-specific therapy group vs 6.6 months (95% CI = 5.5–7.9 months) in the empirical therapy group (hazard ratio [HR] = 0.68, 95% CI = 0.49–0.93, P = .017).
Median overall survival was 28.2 months (95% CI = 23.3–46.5 months) in the site-specific therapy group vs 19.0 months (95% CI = 17.1–26.4 months) in the empirical chemotherapy group (HR = 0.74, 95% CI = 0.52–1.06). Of 117 deaths attributed to CUP, 53 occurred in the site-specific therapy group and 64 occurred in the empirical chemotherapy group.
Among the 167 patients who started planned treatment, 46 (56%) of 82 in the site-specific therapy group and 52 (61%) of 85 in the empirical chemotherapy group had grade ≥ 3 treatment-related adverse events; the most common were decreased neutrophil count (44% vs 49%), decreased white blood cell count (21% vs 31%), and anemia (12% vs 11%). Treatment-related serious adverse events occurred in 6% vs 2% of patients. No treatment-related deaths were observed.
The investigators concluded, “This single-center randomized trial showed that site-specific therapy guided by the 90-gene expression assay could improve progression-free survival compared with empirical chemotherapy among patients with previously untreated CUP. Site-specific prediction by the 90-gene expression assay might provide more disease information and expand the therapeutic armamentarium in these patients.”
Xichun Hu, MD, PhD, and Zhiguo Luo, MD, of the Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, are the corresponding authors for The Lancet Oncology article.
Disclosure: The study was funded by the Clinical Research Plan of Shanghai Hospital Development Center, Program for Shanghai Outstanding Academic Leader, and Shanghai Anticancer Association SOAR PROJECT. For full disclosures of the study authors, visit thelancet.com.
