Adding avelumab to best supportive care improved the median overall survival by over 7 months in patients with locally advanced or metastatic urothelial carcinoma, according to findings from the phase 3 JAVELIN Bladder 100 study.
Thomas Powles, MD
Adding avelumab (Bavencio) to best supportive care (BSC) improved the median overall survival (OS) by over 7 months in patients with locally advanced or metastatic urothelial carcinoma, according to findings from the phase 3 JAVELIN Bladder 100 study presented during the 2020 ASCO Virtual Scientific Program.1,2
The results showed that the addition of the PD-L1 inhibitor reduced the risk of death by 31%. The median OS was 21.4 months with avelumab plus BSC compared with 14.3 months with BSC alone (HR, 0.69; 95% CI, 0.56-0.86; P <.001). The survival benefit with avelumab extended across all prespecified subgroups, including those defined by cisplatin-based or carboplatin-based chemotherapy, and regardless of whether response or stable disease was reached after first-line induction chemotherapy.
EMD Serono (Merck KGaA) and Pfizer, the codevelopers of the PD-L1 inhibitor, previously submitted a supplemental Biologics License Application to the FDA for the use of avelumab in this setting.
“Avelumab first-line maintenance in patients whose disease has not progressed with platinum-based induction therapy is a new first-line standard of care for advanced urothelial carcinoma,” said lead study author Thomas Powles, MD, a professor of genitourinary oncology and director of Barts Cancer Centre in London.
In the multicenter, international, open-label, parallel-arm, randomized, phase 3 JAVELIN Bladder 100 trial, investigators evaluated first-line maintenance therapy with avelumab plus best supportive care (n = 350) versus best supportive care alone (n = 350) in 700 patients with unresectable locally advanced or metastatic urothelial cancer whose disease did not progress following 4 to 6 cycles of standard gemcitabine with either cisplatin or carboplatin.
Randomized patients had achieved a complete response, partial response, or stable disease with chemotherapy. Patients received their treatment between 4 and 10 weeks following induction chemotherapy. Across the study population, 51% (n = 358) of patients had tumors that were PD-L1 positive.
Avelumab was administered intravenously at 10 mg/kg every 2 weeks in 4-week cycles. Best supportive care could include antibiotics, nutritional supportive, correction of metabolic disorders, and symptom control and pain management. The coprimary end points were OS in all randomized patients and in those with PD-L1—positive tumors. Secondary end points included progression-free survival (PFS), antitumor activity, safety, pharmacokinetics, immunogenicity, predictive biomarkers, and patient-reported outcomes in the coprimary populations.
The median follow-up was 19.6 months for the avelumab cohort and 19.2 months for the BSC-alone cohort. Among patients with PD-L1—positive tumors, the median OS was not reached in the avelumab arm versus 17.1 months in the control arm (HR, 0.56; 95% CI, 0.40-0.79; P = .0003).
Per blinded independent central review, the median PFS in the overall population was 3.7 months with avelumab plus BSC versus 2 months with BSC alone (HR, 0.62; 95% CI, 0.52-0.75; P <.001). The HR for PFS also favored the avelumab arm in the PD-L1—positive subpopulation (HR, 0.56; 95% CI, 0.43-0.73).
The safety analysis comprised 344 patients from the avelumab arm and 345 patients from the BSC-alone arm. “Avelumab was well tolerated. This is very much in line with what we have seen from previous studies of immune checkpoint inhibitors in urothelial cancer,” said Powles.
All-grade “any-cause” adverse events (AEs) occurred in 98% versus 77.7% of the avelumab and control arms, respectively, and grade 3/4 AEs occurred in 47.4% versus 25.2%, respectively. The most common grade ≥3 AEs were urinary tract infection (4.4% vs 2.6% in the avelumab arm vs control arm, respectively), anemia (3.8% vs 2.9%), hematuria (1.7% vs 1.4%), fatigue (1.7% vs 0.6%), and back pain (1.2% vs 2.3%).
“In patients with advanced urothelial cancer, recurrence frequently happens following initial treatment with chemotherapy. This study shows the largest survival benefit seen to date in advanced urothelial cancer. When used as a maintenance therapy, avelumab significantly extended the period of time until recurrence,” ASCO President Howard A. Burris III, MD, FACP, FASCO, stated in a press release.
Avelumab was previously granted an accelerated approval by the FDA in 2017 for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have 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.