Treatment tailored by comprehensive molecular gene-expression analysis of tumors from patients with carcinomas of an unknown primary site did not improve progression-free survival vs empiric chemotherapy consisting of cisplatin/gemcitabine. Fizazi et al presented these findings at the European Society for Medical Oncology (ESMO) 2019 Congress (Abstract LBA15).

Karim Fizazi, MD, PhD

Patients with carcinomas of an unknown primary site generally have poor outcomes, even though empiric chemotherapy with broad activity against a wide variety of neoplasms is available and has demonstrated efficacy, according to presenting author Karim Fizazi, MD, PhD, of Institut Gustave Roussy, and as shown by Culine et al in the Journal of Clinical Oncology. He also noted that molecular tests identify primary sites in up to 80% of patients, and results published by Gross-Goupil et al in the European Journal of Cancer suggested that at least one-third of identified primaries may not be sensitive to empiric chemotherapy used in carcinomas of an unknown primary site.

Dr. Fizazi and colleagues hypothesized that treatment tailored to the suspected primary site of origin may improve patient outcomes.

Methods

The phase III GEFCAPI 04 trial (2011-A01202-39) enrolled treatment-naive patients with pathologically confirmed metastatic carcinomas of the unknown primary site. Patients in predefined subsets with a more favorable prognosis were excluded from enrollment.

Patients undergoing a relevant workup that identified no primary site were randomly assigned 1:1 to arm A for treatment with cisplatin at 100 mg/m² on day 1 plus gemcitabine at 1,250 mg/m² on days 1 and 8 every 3 weeks (n = 120) or to arm B, where they were given a gene-expression test followed by treatment tailored to the suspected primary site (n = 123). A total of 21 patients received the Tissue of Origin test, and 222 received the CancerTYPE ID test.

The primary endpoint of the study was progression-free survival. Stratification was performed according to site, performance status, and baseline lactic acid dehydrogenase level. Secondary endpoints were progression-free survival in patients with predefined cancers that were likely to be insensitive to cisplatin/gemcitabine and overall survival.

Methods

Molecular testing most often identified pancreaticobiliary cancer (19%), squamous cell carcinoma (11%), kidney cancer (8%), and lung cancer (8%) as the primary cancer.

Treatment tailored by the molecular test results was administered to 91 of 123 patients (74%) in arm B.

Progression-free survival by central review in patients in arm B was similar to that of patients in arm A receiving gemcitabine/cisplatin; median progression-free survival was 5.3 months vs 4.6 months, respectively (hazard ratio [HR] = 0.95, 95% confidence interval [CI] = 0.72–1.25; P = .7). No significant difference in progression-free survival was observed between the treatment groups according to local review—median progression-free survival by local review was 5.8 months in arm B vs 6.4 months in arm A (HR = 0.80, 95% CI = 0.60–1.06; P = .12).

The comparison of overall survival in the overall population with a cohort of 60 patients with suspected cancers likely to be insensitive to gemcitabine/cisplatin showed similar results—median overall survival was 10.0 months vs 10.7 months (HR = 0.92, 95% CI = 0.69–1.23).

The authors concluded, “In GEFCAPI 04, using a molecular test followed by tailored systemic treatment did not improve outcomes of patients with carcinomas of the unknown primary site.”

Disclosure: GEFCAPI 04 received funding from the Programme Hospitalier de Recherche Clinique (PHRC) from the French Ministry of Health. For full disclosures of the study authors, visit esmo.org.