Andrea Apolo, MD
The PD-L1 inhibitor avelumab (Bavencio) induced an overall response rate of 17% in patients with platinum-refractory metastatic urothelial carcinoma, according to results from the phase I JAVELIN Solid Tumor study now published in the Lancet Oncology.
The 17% (95% CI, 11-24) ORR occurred among 161 patients who had been followed for at least 6 months. Nine patients (6%) had a complete response (CR) and 18 (11%) had partial responses according to independent review. The disease control rate was 40% per independent review, including 37 patients who had stable disease as their best response. Twenty-two percent (n = 35) had tumor size reduction of 30% or more from baseline.
The findings from the JAVELIN Solid Tumor study previously supported the FDA’s May 2017 accelerated approval of avelumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma with disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.
“Overall, our findings suggest that avelumab is generally well tolerated and shows promising antitumor activity in patients with platinum-refractory metastatic urothelial carcinoma,” wrote corresponding author Andrea Apolo, MD, a medical oncologist at the National Cancer Institute and chief of the bladder cancer section of the Genitourinary Malignancies Branch.
In the JAVELIN Solid Tumor study, 249 patients with locally advanced or metastatic urothelial carcinoma received treatment with avelumab for a median of 12 weeks (IQR, 6.0-19.7) and were followed for a median of 9.9 months (range, 4.3-12.1). The median patient age was 68 years (range, 63-76), 72% of patients were male, and 78% were white. The ECOG performance status was 0 and 1 for 35% and 66% of patients, respectively. The median number of prior therapies was 2.
Avelumab was administered at 10 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity. Prior to each avelumab administration, all patients received an antihistamine and acetaminophen.
Among the 249 patients, there were 161 patients who had progressed after at least one previous platinum-based chemotherapy and were followed for at least 6 months. In these patients, the median time to response was 11.4 weeks (IQR, 5.9-17.4) in patients with a confirmed response per independent review and median duration of response was not reached by data cutoff (95% CI, 42.1 weeks to not estimable). Responses were observed regardless of PD-L1 expression status.
Responses were durable and the estimated proportion of responses lasting at least 24 weeks was 96% (95% CI, 75-99). Based on immune-related response criteria, the duration of response was not reached by data cutoff (95% CI, 42.1 weeks to not estimable), and the estimated proportion of responses lasting at least 24 weeks was 96% (95% CI 73-99). Twenty-two (82%) of 27 patients had ongoing responses at data cutoff (range, 6.1-75.6 weeks), including in 8 of 9 patients with a CR.
The median progression-free survival per independent review was 6.3 weeks (95% CI, 6.0-10.1) and 23% of patients were progression free at 24 weeks (95% CI, 17-30). At the time of analysis, 94 patients had experienced disease progression and 30 had died.
Nearly all patients (98%) experienced an any-grade adverse event (AE), including in 166 (67%) who had a treatment-related AE. The most frequent (≥10%) all-grade treatment-related AEs were infusion-related reaction (29%) and fatigue (16%). Twenty-one patients (8%) had a grade ≥3 treatment-related AE, most commonly fatigue (2%), and asthenia, elevated lipase, hypophosphatemia, and pneumonitis (1% each).
The ongoing phase III JAVELIN Bladder 100 trial (NCT02603432) is examining avelumab as a maintenance therapy in patients with locally advanced or metastatic urothelial cancer whose disease did not progress after completion of first-line platinum-containing chemotherapy.
Patel MR, Ellerton J, Infante JR, et al. Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial [published online December 7, 2017]. Lancet Oncol. 2018;19(1):51-64. doi: 10.1016/S1470-2045(17)30900-2.