Avelumab as second-line therapy for metastatic, platinum-treated urothelial carcinoma in the phase Ib JAVELIN Solid Tumor study: 2-year updated efficacy and safety analysis

Abstract

BackgroundAnti-programmed cell death ligand 1 (PD-L1)/programmed cell death 1 antibodies have shown clinical activity in platinum-treated metastatic urothelial carcinoma, resulting in regulatory approval of several agents, including avelumab (anti-PD-L1). We report ≥2-year follow-up data for avelumab treatment and exploratory subgroup analyses in patients with urothelial carcinoma.MethodsPatients with previously treated advanced/metastatic urothelial carcinoma, pooled from two cohorts of the phase Ib JAVELIN Solid Tumor trial, received avelumab 10 mg/kg every 2 weeks until disease progression, unacceptable toxicity or withdrawal. End points included best overall response and progression-free survival (PFS) per RECIST V.1.1, overall survival (OS) and safety. Post hoc analyses included objective response rates (ORRs) in subgroups defined by established high-risk/poor-prognosis characteristics and association between time to response and outcome.Results249 patients received avelumab; efficacy was assessed in 242 postplatinum patients. Median follow-up was 31.9 months (range 24–43), and median treatment duration was 2.8 months (range 0.5–42.8). The confirmed ORR was 16.5% (95% CI 12.1% to 21.8%; complete response in 4.1% and partial response in 12.4%). Median duration of response was 20.5 months (95% CI 9.7 months to not estimable). Median PFS was 1.6 months (95% CI 1.4 to 2.7 months) and the 12-month PFS rate was 16.8% (95% CI 11.9% to 22.4%). Median OS was 7.0 months (95% CI 5.9 to 8.5 months) and the 24-month OS rate was 20.1% (95% CI 15.2% to 25.4%). In post hoc exploratory analyses, avelumab showed antitumor activity in high-risk subgroups, including elderly patients and those with renal insufficiency or upper tract disease; ORRs were numerically lower in patients with liver metastases or low albumin levels. Objective response achieved by 3 months versus later was associated with longer OS (median not reached (95% CI 18.9 months to not estimable) vs 7.1 months (95% CI 5.2 to 9.0 months)). Safety findings were consistent with previously reported 6-month analyses.ConclusionsAfter ≥2 years of follow-up, avelumab showed prolonged efficacy and acceptable safety in patients with platinum-treated advanced/metastatic urothelial carcinoma, including high-risk subgroups. Survival appeared longer in patients who responded within 3 months. Long-term safety findings were consistent with earlier reports with avelumab treatment in this patient population.

Case Report: Anlotinib Combined With Sintilimab as Third-Line Treatment in a Metastatic Urothelial Bladder Carcinoma Patient With FGFR3 Mutation

“…The prognosis of patients with mUBC is very poor if the disease progresses after platinum-based chemotherapy ( 1 ). The immune checkpoint inhibitors programmed cell death ligand-1 (PD-L1)/programmed death-1 (PD-1) are clinically active reagents for mUBC.…”

Cancer Immunotherapy Update: FDA-Approved Checkpoint Inhibitors and Companion Diagnostics

“…This was the first treatment for mMCC, with an ORR of 46.7% (87). Avelumab was then approved for the treatment of urothelial carcinoma patients and for the treatment of patients with advanced renal cell carcinoma (88). Though PD-L1 expression was evaluated and demonstrated an increase in ORR correlated with expression levels, the ORR was achieved in all expression cohorts.…”

“…Though PD-L1 expression was evaluated and demonstrated an increase in ORR correlated with expression levels, the ORR was achieved in all expression cohorts. OS was not found to be correlated with PD-L1 expression; therefore, the protein expression was not considered predictive (88).…”

Current Trends and Future Prospects of Molecular Targeted Therapy in Head and Neck Squamous Cell Carcinoma

“…Currently, cetuximab, which is an anti-EGFR antibody, and nivolumab and pembrolizumab, which are anti-PD-1 antibodies, have been approved and treated as molecular targeted therapeutic agents that can be used for oral cancer [ 57 ]. In addition, clinical trials of molecular targeted therapeutic agents such as ipilimumab, which is an anti-CTLA-4 antibody [ 58 ], and avelumab and atezolizumab, which are anti-PD-L1 antibodies [ 59 ], have been performed. However, which agent should be used and how much effect can be expected differ from each patient when using these molecular targeted therapeutic agents, and it is considered that there is no response to these agents at all.…”