January 25, 2021 - The European Commission has approved avelumab for use as a frontline maintenance option in the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who did not progress after having received platinum-based chemotherapy.
The European Commission has approved avelumab (Bavencio) for use as a frontline maintenance option in the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who did not progress after having received platinum-based chemotherapy.1
The decision follows data from the prespecified interim analysis of the phase 3 JAVELIN Bladder 100 trial, which showed that first-line maintenance with avelumab plus best supportive care (BSC) resulted in a significant improvement in survival compared with BSC alone, with a median of 21.4 months versus 14.3 months, respectively, in the co-primary population of all randomized participants (hazard ratio [HR], 0.69; 95% CI, 0.56-0.86).2 The same held true for the co-primary population of 358 patients whose tumors were PD-L1 positive (HR, 0.56; 95% CI, 0.40-0.79).2,3
Updated findings, at a data cutoff of January 19, 2020, continued to demonstrate that avelumab prolonged OS in all randomized participants compared with BSC alone (HR, 0.70; 95% CI, 0.56-0.86; two-sided P = .0008). Here, the median OS was 22.1 months in the investigative arm compared with 14.6 months in the control arm.
“Avelumab is the only immunotherapy to demonstrate a significant improvement in OS in the first-line setting in a phase 3 study in advanced or metastatic bladder cancer,” Thomas Powles, MD, director of Barts Cancer Centre, stated in a press release. “With this approval by the European Commission, we can now offer patients a potential new first-line maintenance standard of care that may help them live longer.”
In the multicenter, international, open-label phase 3 trial, investigators evaluated first-line avelumab maintenance plus BSC (n = 350) versus BSC alone (n = 350) in patients with unresectable locally advanced or metastatic urothelial cancer who did not progress on 4 to 6 cycles of standard gemcitabine plus either cisplatin or carboplatin.
Participants included on the trial achieved a complete response, a partial response, or stable disease when given chemotherapy. Patients received treatment between 4 to 10 weeks following induction chemotherapy. Fifty-one percent of patients had PD-L1–positive tumors.
In the trial, investigators administered intravenous avelumab at a dose of 10 mg/kg every 2 weeks in 4-week cycles. BSC comprised antibiotics, nutritional support, correction of metabolic disorders, symptom control, and pain management.
The co-primary end points of the trial included OS in all randomized patients and in the subgroup of patients with PD-L1–positive tumors. Key secondary end points include progression-free survival (PFS), antitumor activity, pharmacokinetics, immunogenicity, predictive biomarkers, safety, and patient-reported outcomes assessed in the co-primary patient populations.
Additional results from the trial showed that the median PFS in the overall patient population was 3.7 months in the investigative arm versus 3.7 months in the control arm per blinded independent central review (HR, 0.62; 95% CI, 0.52-0.75; P <.001). In the subgroup of patients with PD-L1–positive tumors, the HR for PFS was also found to favor the immunotherapy (HR, 0.56; 95% CI, 0.43-0.73).
Avelumab was found to be very well tolerated. Among 344 patients who received the immunotherapy and 345 who received BSC alone, all-grade, any-cause toxicities were reported in 95% versus 77%, respectively. Approximately 47% of patients who received avelumab/BSC experienced grade 3/4 adverse effects versus 25.2% of those who received BSC alone.
The most frequently reported grade 3 or higher toxicities comprised urinary tract infection (4.4% with avelumab/BSC vs 2.6% with BSC alone), anemia (3.8% vs 2.9%, respectively), hematuria (1.7% vs 1.4%), fatigue (1.7% vs 0.6%), and back pain (1.2% vs 2.3%).
In June 2020, the FDA approved avelumab as maintenance for patients with locally advanced or metastatic urothelial carcinoma that has not progressed with frontline platinum-based chemotherapy. In 2017, the immunotherapy was granted accelerated approval from the FDA for the treatment of patients with locally advanced or metastatic urothelial carcinoma who experience progressive disease during or after platinum-containing chemotherapy, or who experience progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.