Avelumab Approved by FDA for Bladder Cancer

The FDA has granted an accelerated approval to the PD-L1 inhibitor avelumab (Bavencio) 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.

The approval was based on data from the urothelial carcinoma cohorts of the single-arm, open-label JAVELIN Solid Tumor trial, in which the overall response rate was 13.3% (95% CI, 9.1-18.4) among 226 patients who had been followed for at least 13 weeks, and was 16.1% (95% CI, 10.8-22.8) among 161 patients who had been followed for at least 6 months.

In the ≥6-month follow-up cohort, the 26 responses included 9 (5.6%) complete responses (CRs) and 17 (10.6%) partial response (PRs). In the ≥13 weeks follow-up group, the 30 responses included 9 CRs (4%) and 21 PRs (9.3%).

The median duration of response had not yet been reached for either arm and ranged from 1.4+ to 17.4+ months for both groups. The median time to response was 2 months (range, 1.3-11.0) for both groups.

PD-L1 expression was evaluable in 84% of patients across both cohorts. Among this population, there was no distinguishable variation in response rates based on tumor expression levels of PD-L1.

The JAVELIN Solid Tumor trial included 242 patients with locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy, or who had disease progression within 12 months of treatment with a platinum-containing neoadjuvant or adjuvant chemotherapy regimen.

The median patient age in the ≥13 weeks follow-up group was 68 years (range, 30-89), 72% of patients were male, and 80% were white. The ECOG performance status was 0 and 1 for 34% and 66% of patients, respectively.

Four percent (9/226) of patients had progressed after receiving prior platinum-containing neoadjuvant or adjuvant therapy only. Twenty percent of patients had received prior cisplatin and carboplatin-based regimens, 47% had only prior cisplatin-based treatment, and 32% had only prior carboplatin-based treatment. Liver metastases were reported in 34% of patients at baseline, and 17% of patients had hemoglobin below 10 g/dL.

Patients enrolled in JAVELIN received avelumab 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.

The most common all-grade adverse events (AEs) were fatigue (41%), infusion-related reaction (30%), musculoskeletal pain (25%), nausea (24%), decreased appetite (21%), and urinary tract infection (21%).

The most frequent grade 3/4 AEs included hyponatremia (16%), fatigue (7%), anemia (6%), hypertension (5%), urinary tract infection (5%), and musculoskeletal pain (3%).

All-grade serious AEs occurred in 41% of patients, with the most frequent including urinary tract infection/urosepsis, abdominal pain, musculoskeletal pain, creatinine increased/renal failure, dehydration, hematuria/urinary tract hemorrhage, intestinal obstruction/small intestine obstruction, and pyrexia.

Avelumab was temporarily and permanently discontinued due to AEs in 29% and 12% of patients, respectively. AE-related deaths occurred in 6% of patients (n = 14), and were due to pneumonitis, respiratory failure, sepsis/urosepsis, cerebrovascular accident, or gastrointestinal AEs.

The accelerated approval of avelumab for this indication is contingent on results from a confirmatory trial.

The ongoing phase III JAVELIN Bladder 100 trial (NCT02603432) is evaluating avelumab in the first-line setting as a maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma.