Site-specific therapy guided by a 90-gene expression assay versus empirical chemotherapy in patients with cancer of unknown primary (Fudan CUP-001): a randomised controlled trial

• Published in: The lancet oncology 2024-08, Vol.25 (8), p.1092-1102
• Main Authors: Liu, Xin, MD, Zhang, Xiaowei, MD, Jiang, Shiyu, MD, Mo, Miao, MM, Wang, Qifeng, MD, Wang, Yanli, MM, Zhou, Liangping, MD, Hu, Silong, MD, Yang, Huijuan, Prof, Hou, Yifeng, MD, Chen, Yong, Prof, Lu, Xueguan, MD, Wang, Yu, MD, Zhou, Xiaoyan, Prof, Li, Wentao, MD, Chang, Cai, Prof, Yang, Xiujiang, MD, Chen, Ke, MD, Cao, Jun, MD, Xu, Qinghua, PhD, Sun, Yifeng, MSc, Luo, Jianfeng, MD PhD, Luo, Zhiguo, MD, Hu, Xichun, Prof
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adolescent; Adult; Adverse events; Aged; Angina pectoris; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers; Cancer therapies; Carboplatin; Carboplatin - administration & dosage; Cardiovascular disease; Cell differentiation; Chemotherapy; China; Cisplatin; Cisplatin - administration & dosage; Cisplatin - therapeutic use; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Female; Gemcitabine; Gene expression; Gene Expression Profiling; Hematology, Oncology, and Palliative Medicine; Humans; Hypotheses; Immunotherapy; Intravenous administration; Leukocytes (neutrophilic); Male; Medical imaging; Medical prognosis; Metastases; Metastasis; Middle Aged; Neoplasms, Unknown Primary - drug therapy; Neoplasms, Unknown Primary - genetics; Neoplasms, Unknown Primary - mortality; Neoplasms, Unknown Primary - pathology; Oncology; Patients; Platinum; Population studies; Squamous cell carcinoma; Standard of care; Taxoids - administration & dosage; Taxoids - therapeutic use; Translation; Tumors; Young Adult
• ISSN: 1470-2045; 1474-5488; 1474-5488
• DOI: 10.1016/S1470-2045(24)00313-9

SummaryBackgroundEmpirical chemotherapy remains the standard of care in patients with unfavourable cancer of unknown primary (CUP). Gene-expression profiling assays have been developed to identify the tissue of origin in patients with CUP; however, their clinical benefit has not yet been demonstrated. We aimed to evaluate the efficacy and safety of site-specific therapy directed by a 90-gene expression assay compared with empirical chemotherapy in patients with CUP. MethodsThis randomised controlled trial was conducted at Fudan University Shanghai Cancer Center (Shanghai, China). We enrolled patients aged 18–75 years, with previously untreated CUP (histologically confirmed metastatic adenocarcinoma, squamous cell carcinoma, poorly differentiated carcinoma, or poorly differentiated neoplasms) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, who were not amenable to local radical treatment. Patients were randomly assigned (1:1) by the Pocock and Simon minimisation method to receive either site-specific therapy or empirical chemotherapy (taxane [175 mg/m 2 by intravenous infusion on day 1] plus platinum [cisplatin 75 mg/m 2 or carboplatin area under the curve 5 by intravenous infusion on day 1], or gemcitabine [1000 mg/m 2 by intravenous infusion on days 1 and 8] plus platinum [same as above]). The minimisation factors were ECOG performance status and the extent of the disease. Clinicians and patients were not masked to interventions. The tumour origin in the site-specific therapy group was predicted by the 90-gene expression assay and treatments were administered accordingly. The primary endpoint was progression-free survival in the intention-to-treat population. The trial has been completed and the analysis is final. This study is registered with ClinicalTrials.gov ( NCT03278600). FindingsBetween Sept 18, 2017, and March 18, 2021, 182 patients (105 [58%] male, 77 [42%] female) were randomly assigned to receive site-specific therapy (n=91) or empirical chemotherapy (n=91). The five most commonly predicted tissues of origin in the site-specific therapy group were gastro-oesophagus (14 [15%]), lung (12 [13%]), ovary (11 [12%]), cervix (11 [12%]), and breast (nine [10%]). At the data cutoff date (April 30, 2023), median follow-up was 33·3 months (IQR 30·4–51·0) for the site-specific therapy group and 30·9 months (27·6–35·5) for the empirical chemotherapy group. Median progression-free survival was significantly longer with site-specif