medwireNews: Enfortumab vedotin (EV) is associated with better advanced urothelial cancer outcomes than standard chemotherapy even in patients with poor prognostic factors, suggests a subgroup analysis of the EV-301 study presented at the ESMO Congress 2021.
These results follow a preplanned interim analysis showing a significant overall survival (OS) advantage with the nectin-4-targeted antibody–drug conjugate versus single-agent chemotherapy in the total study population comprising 608 patients previously treated with platinum-based chemotherapy and checkpoint inhibitors (hazard ratio [HR] for death=0.70).
The current analysis – presented in a poster by Jonathan Rosenberg (Memorial Sloan Kettering Cancer Center, New York, USA) and colleagues – focuses on four “hard-to-treat” subgroups defined by:
- age of at least 65 years (n=389);
- presence of liver metastases (n=188);
- primary upper tract disease (n=205); or
- nonresponse to PD-1 or PD-L1 inhibitor (n=422).
Treatment with EV at a dose of 1.25 mg/kg on days 1, 8, and 15 of each 28-day cycle offered a significant OS benefit over treatment with either docetaxel 75 mg/m2, paclitaxel 175 mg/m2, or vinflunine 320 mg/m2 every 3 weeks in patients aged at least 65 years, those with liver metastases, and those unresponsive to prior checkpoint inhibitors, with HRs of 0.75, 0.66, and 0.76, respectively.
OS also favored EV in the subgroup of patients with primary upper tract disease, at an HR of 0.85, but this result was not statistically significant.
The progression-free survival results were similar, with significant HRs for progression or death of 0.62, 0.60, and 0.70 in the subgroups defined by age of at least 65 years, presence of liver metastases, and nonresponse to checkpoint inhibition, respectively, and a nonsignificant HR of 0.72 in the primary upper tract disease subgroup.
And the overall response rate was “consistently higher” with EV than chemotherapy across all subgroups, reported Rosenberg et al, with significant absolute differences between treatments ranging from 20.9 percentage points for patients aged 65 years or older to 24.8 percentage points for those with primary upper tract disease.
Treatment-related adverse events of grade 3–5 occurred at rates of 47.8–59.4% with EV and 41.3–53.7% with chemotherapy across the subgroups.
Rosenberg and co-investigators pointed out, however, that after adjustment for treatment exposure, the incidence of such events was lower with EV than chemotherapy in all four subgroups, at 2.3–3.1 events per patient year versus 3.5–4.7 events per patient year.
“These data support the consistency of EV effects and use in previously treated patients with [locally advanced or metastatic urothelial carcinoma], including those with poor prognostic factors,” they concluded.
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This independent news story was supported by an educational grant from Pfizer and Merck Healthcare KGaA, Darmstadt, Germany