The subgroup analysis assessed data from the pivotal phase 3 JAVELIN Bladder 100 trial showed.
Subgroup data from the pivotal phase 3 JAVELIN Bladder 100 trial showed that frontline maintenance with avelumab (Bavencio) plus best supportive care (BSC) improved median overall survival (OS) in Japanese patients with advanced urothelial cancer.1
The trial enrolled patients who had not progressed on frontline chemotherapy and randomized them to avelumab plus BSC versus BCS alone. The subgroup findings showed a median OS of 24.7 months versus 18.7 months in patients who received the combination (n = 36) versus BSC alone (n = 37), respectively (HR, 0.81). In Japanese patients with PD-L1–positive tumors, the median OS was 18.6 months and 19.4 months, respectively (HR, 1.00; 95% CI, 0.41-2.41). However, the 95% confidence intervals were wide due to the small number of patients.
The findings were consistent with the overall study population of JAVELIN Bladder 100, lead study author Norihiko Tsuchiya, MD, of the Department of Urology at Yamagata University Faculty of Medicine, and co-investigators, stated in a poster presentation during the 2021 Genitourinary Cancers Symposium.
“The interpretation of findings in the Japanese subgroup is limited by the small number of patients compared with the overall trial population,” Tsuchiya noted. “Overall, these results support the consideration of avelumab [as first-line] maintenance as a potential new standard of care in Japanese patients with advanced urothelial cancer that has not progressed with [first-line] platinum-containing chemotherapy.”
In the phase 3 JAVELIN Bladder 100 study (NCT02603432), investigators sought to determine the efficacy and safety of avelumab plus BSC versus BSC alone as a frontline maintenance therapy in 700 patients with locally advanced or metastatic urothelial cancer that did not progress on frontline chemotherapy with cisplatin/gemcitabine or carboplatin/gemcitabine.
Following a treatment-free interval of 4 to 10 weeks, patients were randomized to receive avelumab at 10 mg/kg intravenously every 2 weeks plus BSC or BSC alone until disease progression, unacceptable toxicity, or withdrawal.
PD-L1 status was defined using the Ventana SP263 immunohistochemistry assay. Patients were stratified by best response to first-line chemotherapy (complete response [CR] or partial response [PR] vs stable disease [SD]).
The primary end point of the trial was OS in the primary analysis populations, which included all randomized patients and PD-L1–positive patients. Secondary end points were progression-free survival (PFS) and objective response rate (ORR) per RECIST v1.1 criteria by blinded independent central review, safety and tolerability, and patient-reported outcomes.
Overall results, which were presented at the 2020 ASCO Virtual Scientific Program, showed that avelumab plus BSC demonstrated significantly prolonged OS versus BSC alone (HR, 0.69; P <.001). The benefit was also seen in PD-L1–positive patients (HR, 0.56; P = .0003).2 Based on these data, the FDA approved the combination of avelumab and BSC in June 2020 as a frontline maintenance regimen in this setting.3
In this analysis, investigators evaluated the outcomes of all patients enrolled in sites in Japan (n = 73) in the same trial. Baseline characteristics of Japanese patients compared with the overall population were similar; however, of note, Japanese patients weighed less (62.9 kg on avelumab and 61.9 kg on BSC) versus the overall group (72.4 kg and 73.0 kg, respectively) and were more likely to have upper tract disease as the site of their primary tumor (Japanese, 58.3% and 56.8%; overall, 30.3% and 23.1%). Japanese patients were also less likely to have received gemcitabine/carboplatin as their first-line chemotherapy regimen (Japanese, 25.0% and 21.6%; overall, 42.0% and 34.9%) and were less likely to experience a CR or PR to first-line chemotherapy (Japanese, 61.1% and 59.5%; overall, 72.3% and 72.0%).
Additional findings showed that the median PFS in Japanese patients was 5.6 months with avelumab/BSC compared with 1.9 months with BSC alone (HR, 0.63). In PD-L1–positive patients who were Japanese, the median PFS was 5.6 months and 1.9 months, respectively (HR, 0.62).
In all Japanese patients, the ORR in the avelumab/BSC arm was 5.6% versus 0% with BSC. The ORR on the avelumab arm was comprised of 1 CR and 1 PR; 3 patients had stable disease, 7 patients had non-CR/non-progressive disease (PD), 17 patients had PD, and 7 patients were not evaluable. The disease control rates were 33.3% and 27.0% with avelumab/BSC and BSC alone, respectively. The response rate data were comparable with the overall study population.
Twenty-two (61.1%) Japanese patients on avelumab/BSC discontinued treatment and received subsequent therapy compared with 30 (81.1%) on BSC alone. In the avelumab arm, subsequent therapy included a PD-1/PD-L1 inhibitor (38.9%), FGFR inhibitor (2.8%), and other (52.8%); these rates were 67.6%, 0%, and 54.1% in the BSC-alone arm. The investigators noted that more Japanese patients on BSC received a subsequent checkpoint inhibitor compared with the overall study population (43.7%).
Regarding safety, the tolerability in the avelumab arm was consistent with the overall study population, and no safety concerns in the Japanese subgroup was identified. All-grade treatment-emergent adverse effects (TEAEs) occurred in 100% of patients on avelumab and 56.8% on BSC; grade 3 or higher TEAEs occurred in 50.0% and 8.1% of patients, respectively. On avelumab, these included anemia (11.1%), pyelonephritis (5.6%), urinary tract infection (2.8%), increased amylase (5.6%), increase in blood triglycerides (5.6%), and fatigue (2.8%).
TEAEs led to treatment discontinuation in 4 patients on avelumab, and 1 patient died due to sepsis.
All-grade treatment-related AEs (TRAEs) occurred in 75% (n = 27) of patients on avelumab, and 5 patients were reported as having TRAEs grade 3 or higher. Immune-related AEs were reported in 36.1% of avelumab-treated patients, 8.3% of which were grade 3. Additionally, 27.8% of patients on this arm had grade 1/2 infusion-related reactions.
1. Tsuchiya N, Yamaoto Y, Uemura H, et al. Avelumab first-line maintenance plus best support care (BSC) vs BSC alone for advanced urothelial carcinoma: JAVELIN Bladder 100 Japanese subgroup analysis. J Clin Oncol. 2021;39(suppl 6):425. doi:10.1200/JCO.2021.39.6_suppl.425
2. Powles T, Park SH, Voog E, et al. Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis. J Clin Oncol. 2020;38(suppl 18):LBA1. doi:10.1200/JCO.2020.38.18_suppl.LBA1
3. FDA approves Bavencio as first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma. News release. Pfizer. June 30, 2020. Accessed March 1, 2021. https://bit.ly/2YO7gVk.