The efficacy profile for avelumab in patients with locally advanced or metastatic urothelial carcinoma was consistent in a real-world setting with what had been reported in the phase 3 JAVELIN Bladder 100 trial.
Real-world data supports front-line maintenance with avelumab (Bavenzio) for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) following platinum-based chemotherapy, according to findings from an Italian compassionate use program which were presented during the 2023 Genitourinary Cancers Symposium.1
In a population of 411 patients with la/mUC who received avelumab in an Italian compassionate use program, many of whom had upper tract UC or received carboplatin-based chemotherapy, the median overall survival (OS) was not reached. The 12-month OS rate was 69.2% (95% CI, 64.8%-73.7%). The median progression-free survival (PFS) was 8.1 months (95% CI, 6.1-10.4). The 12-month PFS rate was 44.3% (95% CI, 39.5%-49.1%). Thirty-three patients (7.1%) developed all-cause grade 3 or 4 adverse events during treatment.
“Avelumab [as] frontline maintenance provided clinical benefits and had a manageable safety profile in Italian patients with la/mUC, consistent with findings from the phase 3 JAVELIN Bladder 100 trial [NCT02603432],” Lorenzo Antonuzzo, MD, of the Azienda Ospedaliero-Universitaria Careggi, in Florence, Italy, and co-investigators wrote in the paper. “Overall, these real-world data provide further support for avelumab frontline maintenance as standard of care in eligible patients with la/mUC.”
The phase 3 JAVELIN Bladder 100 trial demonstrated that first line maintenance with avelumab, along with best supportive care, propelled OS and PFS in patients with la/mUC compared with best supportive care alone. The study included patients who had received frontline platinum-based chemotherapy and whose disease had not progressed following that treatment.
Long-term follow-up findings from JAVELIN Bladder 100 (over 38 months in both arms) showed that the median OS was 23.8 months with avelumab and 15.0 months with supportive care alone (HR, 0.76; 95% CI, 0.631-0.915; P = .0036). The median PFS, between the 2 arms, respectively, was 5.5 months vs 2.1 months (HR, 0.54; 95% CI; 0.457-0.645; P < .0001).
Following the reports from JAVELIN Bladder 100, governing bodies approved avelumab in many countries, including in the United States and Italy, and it is now recommended as standard of care in international treatment guidelines.1-3
However, as part of an Italian compassionate use program, a portion of patients with la/mUC from across 140 different Italian medical centers were able to receive avelumab treatment before reimbursement from the Italian Medicines Agency became available. This prospective, noninterventional, multicenter study was conducted between January 18, 2021, and March 7, 2022. Of note, the treatment had been approved by the European Commission on January 25, 2021, and reimbursement has been made available in Italy since March 18, 2022.
To be eligible for the program, patients needed to be at least 18 years of age, have unresectable la/mUC (Stage IV), no disease progression following 4 to 6 cycles of platinum-based chemotherapy, and to have received their last dose of chemotherapy 4 to 10 weeks prior to starting avelumab. They also needed an ECOG PS of 0 to 1, adequate bone marrow, renal, and liver function, and not be eligible for any other clinical trial for urothelial carcinoma.
Exclusion criteria comprise of the following: prior adjuvant or neoadjuvant systemic therapy within 12 months, prior treatment with an immune checkpoint inhibitor, and a contradiction to avelumab. All participating patients needed to sign informed consent from the start of treatment, and avelumab was provided per physician request and after approval by local ethics committees. The dose was 800 mg administered intravenously every 2 weeks.
Baseline demographics, disease characteristic, characteristics of frontline chemotherapy, OS, PFS, and safety were all collected. OS was defined as the time form the start of avelumab to death from any cause, and PFS was defined as the time from the start of avelumab until disease progression or death of any cause—whichever came first.
Overall, 466 patients received frontline avelumab maintenance between January 2021 and March 2022. The patient population included 364 male patients (78.5%), 346 patients with metastatic disease and 321 patients with an ECOG PS of 0 (69.2%). The median age was 70.0 years (interquartile range [IQR], 63-76). For 66.6% of patients, the primary tumor was in the lower tract, and for 31.9% of patients the primary tumor was in the upper tract.
Fifty-one-point nine percent of patients had carboplatin and gemcitabine as their frontline chemotherapy regimen and 46.1% of patients had received cisplatin plus gemcitabine. Forty-eight-point five percent of patients had received 4 cycles of platinum-based chemotherapy; whereas 11.6% had received 5 cycles, and 38.2% had received 6 cycles. Moreover, 11.0% of the patients had achieved a complete response with their frontline chemotherapy; 57.3% had reached a partial response, and 31.7% had achieved stable disease status.
Among 386 patients, the median time from the end of frontline chemotherapy to avelumab maintenance initiation was 8.0 weeks (IQR, 6.0-9.0). The median duration for all patients was 5.3 months (IQR, 2.4-9.1), and at data cutoff, 411 patients were eligible for OS and PFS assessment.
Study authors noted that safety events may have been unreported because they were reported at the treating physician’s discretion. They also acknowledged that the duration of follow-up was limited. Regardless, they stated that these findings were sampled from clinical centers that are representative of daily clinical practice and the findings demonstrate a clinical benefit for a group of patients which included patients with upper tract UC and who had received carboplatin-based chemotherapy.