In an interview with Targeted Oncology, Philippe Barthelemy, MD, discussed the preliminary findings of the AVENANCE trial of avelumab in patients with advanced or metastatic urothelial carcinoma.
Early results from the real-world AVENANCE study (NCT02603432)shows clinical activity and acceptable safety profile with avelumab (Bavencio) patients with advanced or metastatic urothelial carcinoma in a heterogeneous population outside of a clinical trial setting.
Findings come from the preliminary analysis of the multicenter, ambispective, non-interventional study which were presented in a poster at the European Society for Medical Oncology Congress 2022. Investigators reported on the 267 patients who were given avelumab at least 6 months before data cutoff.
Among those enrolled in the trial, the median age of patients was 73.1 years (range, 66.7-77.9), the majority were men (81.3%), had metastatic disease (90.5%), and had an ECOG performance status at the start of chemotherapy of 0-1 in (85.5%). More than half (58%) of patients were administered carboplatin plus gemcitabine chemotherapy. Another 31.8% received cisplatin plus gemcitabine, and 10.7% were administered another platinum-based chemotherapy regimen.
Findings showed that 56 patients given first-line platinum-based chemotherapy had a complete response (21.6%), while 144 (55.6%) had a partial response, and 52 (20.1%) had stable disease. The median duration of treatment was 5.8 months and 34.5% of patients continued to receive treatment at a median follow-up of 13.5 months.
The primary end point of the trial, which is overall survival (OS) from the start of avelumab treatment, was a median of 20.7 months (95% CI, 15.2- NE). The 12-month OS rate from the time avelumab was initiated was 66.9% vs 79.1% from the start of chemotherapy. Further, median progression-free survival (PFS) from the start of avelumab was 5.7 months. These findings were comparable with data from the JAVELIN Bladder 100 trial.
Regarding safety, treatment-related adverse events (TRAEs) were experienced in 38.2% of patients and serious TRAEs were reported in 5.2%. TRAEs leading to temporary or permanent treatment discontinuation occurred in 9.7% of participants. One patient died because of their TRAE.
In an interview with Targeted OncologyTM, Philippe Barthelemy, MD, medical oncologist at the Institut de Cancérologie Strasbourg Europe, further discussed the preliminary findings of the AVENANCE trial of avelumab in patients with advanced or metastatic urothelial carcinoma.
Targeted Oncology: Can you discuss the JAVELIN Bladder 100 trial and why this study was significant for this patient population?
Barthelemy: We performed the AVENANCE trial which is a real-world trial evaluating the safety and efficacy of nivolumab. That's very important since we already have the data from JAVELIN Bladder 100 [NCT02603432], which improved overall survival in very poor patients with bladder cancer. These patients were previously treated with platinum-based chemotherapy for 4-6 cycles and responded or were stable with this chemotherapy. It is very important to prove that we have the same results in routine practice because we have to treat all patients and not only selected patients as we did in the JAVELIN Bladder 100.
What is the background and study design ofthe AVENANCE trial?
It's an ambispective trial evaluating the safety and efficacy of avelumab in routine practice in France. We included 601 patients in 8 months in 83 different cancer centers. In one part of the patients were included retrospectively based on an early access program we had in France and which started 1 month after we had the data coming from the JAVELIN Bladder 100 results. We will pursue the AVENANCE trial by including prospective patients and we now stop the inclusion because we met our 601 patients. The aim was to assess efficacy and to assess safety, and to characterize all these patients we treat in routine practice.
Can you discuss the most recent results of the trial?
We presented the first patient's characteristics, and we see that most patients were treated with carboplatin and gemcitabine before they received avelumab. It was about 60%. Patients are different from those treated in the JAVELIN bladder 100 trial as we have 10% of patients treated with other regimens, especially dose dense. That's specificity in first-line in France, but not only. We also see patients in bad performance status. We have included patients with different metastatic sites. We have 1 patient for the moment with brain metastases, but it is important to mention that it's a preliminary analysis based on 276 patients out of the 600 enrolled patients.
The main information is that progression free survival is 5.7 which is very close to what we had in the JAVELIN Bladder 100 trial. The overall survival with a median follow-up of 30.6 months is expected at about 20 months. That means that at 1-year, the survival weight is 66%. Again, this is very close to what we had in JAVELIN Bladder 100. All this data, PFS and OS, are very consistent with those results we had in the JAVELIN Bladder. That means that even in a more frail population in routine practice, we can have the same results as what we had in a more selective, phase 3 clinical trial.
Regarding toxicity, we have no concerns, no new signals, and we have, as expected, some great 2/3 toxicities, but no unexpected new toxicities. We can conclude that avelumab showed efficacy, clinical activity, good performance, and overall survival. We can also say that we do have as much toxicity as expected. It's safe to use it in routine practice, even in a frailer population.
Based on what you saw in this trial, are outcomes in the real world settings similar to clinical trial settings?
There's no big difference between our results regarding results we already had coming from phase 3 trials. I have to mention that it's a real-world population, so a more frail population, and we expected less efficacy and more toxicity. But that's not the case. We have somehow the same weight concerning survival at 12 months, for example. We have no new signals of toxicity. I think the only thing we need is more follow-up and more patients because it's an interim analysis, the first analysis, with a follow-up of 30 months and 276 patients out of 600 patients. In the next meetings, we will probably give more information regarding overall survival, PFS, and subgroup analysis as well.
Why is there a need for this type of real-world trial in bladder cancer?
I think real-world data are very important because we have results coming from phase 3 trials with a very selected population. But we know that in routine practice, especially in urothelial carcinoma, we have very frail patients, and we need information for those patients on how we should treat them, how we should treat patients with non-urothelial carcinoma with mixed histologies. We don't have all of this data coming from large phase 3 trials and that's why I think it's very important to have such real-world data. Now, we can provide new data on different populations of interest, especially new metastatic sites of patients with a bad performance status or patients with non-urothelial carcinoma subtypes.