The phase 2 California Cancer Consortium trial has reported its final results: a combined regimen of gemcitabine (Gemzar®, Eli Lilly) plus eribulin (Halaven®, Eisai Inc.) shows efficacy in patients with metastatic urothelial carcinoma who are ineligible for cisplatin-based treatment. Many patients with urothelial carcinoma—the most common type of bladder cancer—that has metastasized are ineligible for chemotherapy treatments containing cisplatin. As such, alternatives are needed for this population.
This study, which has now been published in the Journal of Clinical Oncology, enrolled 24 patients who had treatment-naive advanced or recurrent metastatic urothelial carcinoma of the bladder, ureter, or urethra that could not be cured by surgery. Patients had to be ineligible for cisplatin, defined as having grade 2 neuropathy, grade 2 hearing loss, or creatinine clearance less than 60 mL/min, although they were required to have creatine clearance of at least 30 mL/min to participate in the study.
Of the 24 patients, whose median age was 73, 11 patients had a performance status of 0, 11 had a performance status of 1, and 2 had a performance status of 2, with disease sites including the lymph nodes (16 patients) , lungs (9 patients), liver (7 patients), bladder (5 patients), and bones (2 patients).
Patients were treated with 1,000 mg/m2 of intravenous gemcitabine followed by 1.4 mg/m2 of eribulin on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. Patients received a median of 4 cycles of treatment, with a range of 1 cycle to 16 cycles.
Gemcitabine/eribulin produced an objective response rate of 50%, with a median overall survival of 11.9 months and a median progression-free survival of 5.3 months. The most frequent treatment-related adverse events of any grade were fatigue, experienced by 83% of patients; neutropenia, experienced by 79%; anemia, experienced by 63%; alopecia, experienced by 50%; elevated aspartate aminotransferase (AST), experienced by 50%; and constipation, nausea, and thrombocytopenia, each experienced by 42% of patients.
"Gemcitabine-eribulin treatment response and survival for cisplatin-ineligible patients compare favorably to other regimens," conclude the study authors, led by first author Sarmad Sadeghi, MD, PhD, Assistant Professor of Clinical Medicine at the Keck School of Medicine of the University of Southern California. "Additional research is needed."
For More Information
Sadeghi S, Groshen SG, Tsao-Wei DD, et al (2019). Phase II California Cancer Consortium trial of gemcitabine-eribulin combination in cisplatin-ineligible patients with metastatic urothelial carcinoma: final report (NCI-9653). J Clin Oncol. [Epub ahead of print] DOI:10.1200/JCO.19.00861
Image credit: Andrew M. Smith and Hong Yi. Courtesy of the National Cancer Institute