medwireNews: Phase II study data suggest favorable treatment response and survival with first-line gemcitabine–eribulin in cisplatin-ineligible patients with metastatic urothelial carcinoma.
“The combination of gemcitabine and eribulin was well tolerated and met the prespecified trial end point for activity on the basis of a 50% overall response rate in cisplatin-ineligible patients with urothelial carcinoma,” say Sarmad Sadeghi (University of Southern California, Los Angeles, USA) and team.
They highlight in the Journal of Clinical Oncology that the “study met its primary end point even before enrolling 21 patients,” which was the total number the researchers initially intended to accrue.
The single-arm study, NCI-9653, included data from 24 patients with locally advanced, unresectable, or metastatic urothelial carcinoma, who were ineligible for cisplatin due to having a creatinine clearance of between 30 and 60 mL/min, grade 2 neuropathy, or grade 2 hearing loss.
Participants received a median of four 21-day treatment cycles comprising 1000 mg/m2 of gemcitabine followed by 1.4 mg/m2 of eribulin, on days 1 and 8 of each cycle. Depending on toxicity, doses were reduced on an individual basis. After treatment ended, patient follow-up occurred every 3 months for up to 36 months.
Of the 19 patients who underwent disease evaluation, one had a complete response and 11 had a partial response to the combination treatment. Therefore, 12 of the 24 patients were confirmed responders, giving an objective response rate (ORR) of 50%. The median overall survival (OS) was 11.9 months, and median progression-free survival (PFS) was 5.3 months.
These findings support those of a previous study showing an objective response rate of 34.7% with eribulin as a single agent and a median OS and PFS of 9.5 and 4.1 months, respectively, note the researchers.
Indeed, they add that the current findings suggest a greater benefit with eribulin and gemcitabine combined than with eribulin alone, but acknowledge that “a direct comparison of the efficacy of the single agent versus the combination should be conducted and compared with the standard of care as the control arm.”
Similarly, although the study did not directly compare gemcitabine–eribulin against other regimens, Sadeghi and colleagues infer that the combined treatment compares favorably with gemcitabine and carboplatin – the current standard of care – which has an ORR of 41% in similar patients, and a median OS of 9.1 months.
The most common grade 3 or 4 toxicities associated with gemcitabine–eribulin were neutropenia, anemia, and fatigue, experienced by 63%, 29%, and 29% of patients, respectively.
“The next step in the development of eribulin in urothelial carcinoma is a phase III study of patients previously treated with or not eligible for T-cell checkpoint therapy with agents directed at PD1 or PDL1,” the team concludes.
By Hannah Kitt
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J Clin Oncol 2019; doi:10.1200/JCO.19.00861