FDA Approves Bavencio for Bladder Cancer

The Food and Drug Administration has granted an accelerated approval to the PD-L1 inhibitor Bavencio (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.

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 percent among 226 patients who had been followed for at least 13 weeks, and was 16.1 percent among 161 patients who had been followed for at least 6 months.

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

The median duration of response had not yet been reached for either arm. The median time to response was 2 months for both groups.

PD-L1 expression was evaluable in 84 percent 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, 72 percent of patients were male, and 80 percent were white. The ECOG performance status was zero and one for 34 percent and 66 percent of patients, respectively.

Four percent 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 percent had only prior cisplatin-based treatment and 32 percent had only prior carboplatin-based treatment. Liver metastases were reported in 34 percent of patients at baseline.

Patients enrolled in JAVELIN received Bavencio at 10 mg/kg intravenously every two weeks until progression or unacceptable toxicity. Prior to each Bavencio administration, all patients received an antihistamine and acetaminophen.

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

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

All-grade serious AEs occurred in 41 percent 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 fever.

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

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