"The key end points were observed response rate in the overall cohort, progression-free and overall survival from EV start in the overall cohort, and as an exploratory end point, overall survival from platinum-based chemotherapy start in the overall cohort," says Amanda Nizam, MD.
In this video, Amanda Nizam, MD, highlights the background and key findings from the study, “Outcomes in patients (pts) with advanced urothelial carcinoma (aUC) treated with enfortumab vedotin (EV) after switch maintenance avelumab (MAv) in the UNITE study,” which was presented at the 2024 ASCO Genitourinary Cancers Symposium in San Francisco, California. Nizam is a medical oncologist in genitourinary oncology at Cleveland Clinic in Cleveland, Ohio.
In this abstract, we looked at patients who received platinum-based chemotherapy and maintenance avelumab and then EV. We wanted to look at outcomes with EV in these patients. As background, enfortumab vedotin was approved in 2019 for patients post-platinum and post-checkpoint inhibitor, refractory to both of those regimens. In 2020, avelumab was approved as maintenance therapy, but the investigational trials that looked at enfortumab vedotin did not include patients whose disease had progressed on avelumab. In looking at this, knowing that there's differing disease biology between patients refractory to platinum chemotherapy and then responses to platinum-based chemotherapy, we examined EV outcomes in patients who had platinum responsive disease and thus received maintenance avelumab.
In this analysis, out of 633 patients in the UNITE registry–which is composed of patients with advanced urothelial carcinoma across 16 US sites treated with novel systemic therapies such as EV and sacituzumab govitecan–we identified 49 patients who receive sequential platinum-based chemotherapy, maintenance avelumab, and then enfortumab vedotin, and we examined their outcomes. The key end points were observed response rate in the overall cohort, progression-free and overall survival from EV start in the overall cohort, and as an exploratory end point, overall survival from platinum-based chemotherapy start in the overall cohort. In the subgroups of interests, we looked at subgroups divided by type of platinum chemotherapy received, best response to platinum-based chemotherapy, time on maintenance avelumab, and then the fourth subgroup was Belmont risk score, which is a validated score for poor prognostic factors in advanced urothelial carcinoma and those patients progressing on platinum-based chemotherapy. Out of all of those subgroups, outcomes were similar except for those with Belmont risk scores 0 or 1–which is less adverse prognostic factors–had better progression-free and overall survival than those with Belmont a score of 2 or 3, which indicated more worse prognostic factors such as liver metastases, anemia, or worse performance status.
Overall what we found–in the evaluable patients there were 41 out of 49 of eligible patients–observed response rate was 54%. If you look at the intention-to-treat population, which would be the 49 patients, the overall observed response rate was 45%. If you compare that to EV-301, while we can't directly compare because EV-301 included patients who weren't responsive to platinum-based chemotherapy, that overall response rate and EV-301 in the intention-to-treat population was 41%. When we look at progression-free survival from EV start, it was 7 months, which is similar to what we saw in EV-301, that was 5.6 months. Overall survival from EV start was 13.3 months again, pretty similar to what we saw on EV-301 which is 12.9 months. As an exploratory end point, we looked at overall survival from platinum-based chemotherapy start, and that was 22.5 months from start of platinum-based chemotherapy. This was not reported out of EV-301, so it was just an exploratory end point. [It] seems a little bit short for what we would expect, but given that our registry is looking at patients who are treated with EV, that's the main goal, we're likely capturing people who are progressing on maintenance avelumab more quickly, and thus, we're capturing them at a lower median time on avelumab than what we would see in the real world. If you look at the Javelin bladder 100 trial, which looked at maintenance avelumab, median time on avelumab was 6 months. In this analysis here, the median time on avelumab was 3 months. So, that's why you're seeing that shorter overall survival from platinum-based therapy start because they're progressing on the maintenance avelumab more quickly. So overall, the findings were pretty consistent with EV-301. Again, the caveat being that our study selected for platinum responsive patients so we can't compare exactly, but it does support using EV post-platinum, post-checkpoint inhibitor, and those with platinum responsive disease.
This transcription has been edited for clarity.