Immunotherapy with avelumab improved survival when given as maintenance therapy in patients whose disease did not progress on platinum-based chemotherapy.
Avelumab (Bavencio) as a maintenance treatment after chemotherapy significantly extended overall survival (OS) inpatients with advanced urothelial cancer, according to findings from thephase III JAVELIN Bladder 100 trial.
The results of the study of best supportive care (BSC) with or without immunotherapy after first-line platinum-based chemotherapy were presented in a presscast in advance of the May 29-31, 2020 American Society of Clinica lOncology (ASCO) Annual Meeting.
Investigators reported that avelumab improved survival by 7.1 months compared with BSC alone in patients with unresectable locally advanced or metastatic urothelial cancer that had responded to or remained stable on chemotherapy. The results represent the largest survival benefit seen to date in advanced urothelial cancer in the maintenance setting, and the first showing efficacy of avelumab immediately after initial chemotherapy, a time when recurrence frequently occurs, ASCO stated in a press release.
Avelumab and other immunotherapies that inhibit PD-1 or PD-L1 are standard second-line treatments for patients in this population whose disease progresses after platinum-based chemotherapy, but only 22% to 55% of eligible patients receive it, with a minority of those gaining a durable clinical benefit, reported the study’s lead author, Thomas Powles, MD, a professor of genitourinary oncology and Director of Barts Cancer Centre in London.
The trial included 700 patients with unresectable locally advanced or metastatic urothelial carcinoma who had experienced no disease progression following 4 to 6 cycles of gemcitabine chemotherapy given with either cisplatin or carboplatin. Of the total population, 350 patients were randomized to receive maintenance avelumab at an IV dose of 10 mg/kg every 2 weeks along with BSC and 350 were assigned to BSC alone. The patients started their study treatment within 10 weeks of completing chemotherapy. They were further stratified into subgroups based on whether they had visceral vs non-visceral disease when they started chemotherapy, and whether they had experienced a complete or partial response to chemotherapy vs stable disease.
The primary endpoint was OS, assessed from randomization in 2 primary populations: all randomized patients and those with PD-L1-positive tumors as evaluated by the Ventana SP263 assay. Secondary endpoints included progression-free survival (PFS), objective response, and safety. Patients were followed for a median of more than 19 months.
Investigators found that avelumab plus BSC generatedamedianOSof21.4monthscomparedwith14.3monthsforBSCalone (hazard ratio [HR], 0.69; 95% CI, 0.56-0.86; 1-sided P = .0005).
In patients whose tumors were PD-L1-positive (n = 358), median OS had not yet been reached in the avelumab group and was 17.1 months in the BSC-alone group (HR, 0.56; 95% CI, 0.40, 0.79; 1-sided P = .0003). An OS benefit was also observed across all prespecified subgroups, although those with visceral disease prior to chemotherapy had worse outcomes than those who started with non-visceral disease.
PFS was 38% better in the avelumab arm compared with the BSC-alone group across all study patients (3.7 vs 2.0 months, respectively) based on blinded independent central review (HR, 0.62; 95% CI, 0.52-0.75, P Ë 0.001) and was 44% improved in the avelumab group compared with the BSC-alone groupin patients with PD-L1-positive tumors (HR, 0.56; 95%CI,0.43-0.73).
“In urothelial cancer, patients have high PD-L1 expression and high tumor mutation burden. Response rates associated with immune therapy are pretty high,” Powles said. “This means that checkpoint inhibitors can work quite well in urothelial cancer.”
The researchers plan to continue to follow patients to see how long response is maintained.
Adverse events of grade 3 or higher occurred in 47.4% of patients who received avelumab plus BSC vs 25.2% in those who received BSC alone. The most common grade 3 or higher adverse events were urinary tract infection, anemia, hematuria, fatigue, and back pain. The safety profile of avelumab was consistent with previous studies of monotherapy, the authors stated.
“Avelumab firstline maintenance in patients whose disease has not progressed with platinum-based induction therapy is a new firstline standard of care for advanced urothelial carcinoma,” Powles said.
Powles T, Park SH, Voog E, et al. Maintenance avelumab + best supportive care versus BSC alone after platinum-based first-line chemotherapy in advanced urothelial carcinoma: JAVELIN Bladder 100 phase III interim analysis. Presented at:2020 ASCO Virtual Scientific Program; May 26, 2020. Abstract LBA1.