FDA Approval Insights: Avelumab in Metastatic Urothelial Carcinoma

Welcome to a very special edition of OncLive® On Air! I’m your host today, Caroline Seymour.

OncLive® On Air is a podcast from OncLive, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

Today, we had the pleasure of speaking with Shilpa Gupta, MD a medical oncologist in the Department of Hematology and Medical Oncology at Cleveland Clinic, to discuss the FDA approval of avelumab (Bavencio) as maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-based chemotherapy.

The June 30, 2020 regulatory decision was based on findings from the pivotal phase 3 JAVELIN Bladder 100 trial, which showed a significant improvement in median overall survival (OS) of 7.1 months with avelumab as frontline maintenance treatment plus best supportive care (BSC) over BSC alone. The results from the trial, which were presented during the 2020 ASCO Virtual Scientific Program, showed a median OS of 21.4 months with avelumab versus 14.3 months with BSC alone; this translated to a 31% reduction in the risk of death in the overall patient population.

Notably, the benefit with avelumab extended across all prespecified subgroups, including those defined by cisplatin- or carboplatin-based chemotherapy, and regardless of whether response or stable disease was achieved after frontline induction chemotherapy.

In the multicenter, international, open-label, parallel-arm, randomized phase 3 trial, investigators examined frontline avelumab maintenance therapy in combination with BSC compared with BSC alone in a total of 700 patients with unresectable, locally advanced or metastatic urothelial cancer whose disease did not progress on 4 to 6 cycles of standard gemcitabine paired with either cisplatin or carboplatin.

Patients enrolled on the trial had experienced a complete response, a partial response, or stable disease with chemotherapy. They received treatment between 4 to 10 weeks post induction chemotherapy. Just more than half of patients, or 51%, had tumors with PD-L1 positivity.

Avelumab was given intravenously at 10 mg/kg every 2 weeks in 4-week treatment cycles. BSC included antibiotics, nutritional support, correction of metabolic disorders, as well as symptom control and pain management.

The co-primary end points of the trial were OS in all randomized patients as well as in those with PD-L1–positive tumors. Secondary end points of the trial included progression-free survival (PFS), antitumor activity, safety, pharmacokinetics, immunogenicity, predictive biomarkers, and patient-reported outcomes in the co-primary patient populations.

The median follow-up was 19.6 months in the avelumab arm and 19.2 months in the BSC-alone arm. Additional results demonstrated that in the cohort of patients with PD-L1–positive tumors, the median OS had not yet been reached in those who received avelumab versus 17.1 months in those who received BSC alone.

In the overall patient population, the median PFS was 3.7 months in the avelumab-plus-BSC arm compared with 3.7 months in the BSC-alone arm per blinded independent central review. Additionally, the hazard ratio for PFS favored avelumab in the PD-L1–positive subgroup, as well.

Regarding safety, investigators examined a total of 344 patients in the avelumab arm and 345 patients in the BSC-alone arm and found avelumab to be very well tolerated. All-grade, any-cause adverse events (AEs) were reported in 95% of those who received avelumab versus 77.7% of those who received the control. Grade 3/4 AEs were experienced by 47.4% and 25.2% of those in the avelumab/BSC and BSC-alone arms, respectively. The most common grade 3 or higher AEs reported in the avelumab and control arms included urinary tract infection, anemia, hematuria, fatigue, and back pain.

Previously, in 2017, avelumab was granted an accelerated approval from the FDA for the treatment of patients with locally advanced or metastatic urothelial carcinoma who experience disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

In an interview with OncLive, Gupta discussed the FDA approval of avelumab in metastatic urothelial carcinoma and key findings from the JAVELIN Bladder 100 study.

This episode is sponsored by Pfizer and EMD Serono.