The FDA has approved avelumab as a maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy, according to a release from the manufacturer.
The approval follows the completion of the phase III JAVELIN Bladder 100 study, which showed a 7.1-month improvement in median overall survival using avelumab as a first-line treatment with best supportive care (BSC) alone. That marks a dramatic improvement from 21.4 months on BSC (95% CI: 18.9 to 26.1) vs. 14.3 months (95% CI: 12.9 to 17.9). Overall survival was measured from time of randomization, after four to six cycles of gemcitabine plus cisplatin or carboplatin, over approximately four months.
A total of 700 patients enrolled in the trial, with half assigned to receive 10mg/kg intravenous infusion of avelumab and BSC and half receiving only BSC. In addition to the primary endpoint, secondary endpoints included progression-free survival, anti-tumor activity, and safety. The patient population did not include people with autoimmune disease or those who required immunosuppression due to another medical condition.
Serious adverse reactions occurred in 28% of patients in the avelumab arm, including urinary tract infection, pain, acute kidney injury, and sepsis. One patient enrolled in the avelumab arm died of sepsis. The most common adverse reactions were fatigue, musculoskeletal pain, urinary tract infection, and rash.
Results of the trial were presented at the ASCO 2020 Virtual Scientific Meeting.
Petros Grivas, MD, PhD, one of the principal investigators, said in the release that the approval is “one of the most significant advances in the treatment paradigm in this setting in 30 years.”
“With a median survival of more than 21 months measured from randomization, the longest overall survival in a phase III trial in advanced urothelial carcinoma, the JAVELIN Bladder 100 regimen with avelumab as a first-line switch maintenance treatment has the potential to become a new standard of care based on its proven ability to reinforce the benefit (response or stable disease) of induction chemotherapy and extend the lives of patients with this devastating disease,” Grivas said in the release.
The release notes that most patients experience disease progression within nine months of starting platinum-based chemotherapy and that only 5% of patients with metastatic disease at the time of diagnosis live longer than five years. With the approval, avelumab can be used as a first-line treatment until disease progression or unacceptable toxicity.
Avelumab was previously approved for patients with advanced or metastatic UC who have disease progression during or after platinum-containing chemotherapy, or those who have disease progression within a year of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy, based on tumor response rate and the duration of response, according to the release.
