Andrea Necchi, MD
As the number of tumor types with approved PD-1/PD-L1 pathway inhibitors continues to expand, bladder cancer has become a robust area of development. In less than a year, 2 new checkpoint immunotherapy agents have been approved and 3 others remain under study.
The pathway has emerged as a rational target in urothelial carcinoma (UC), the most common form of bladder cancer, because of the presence of PD-L1 expression and a comparatively high mutation load, researchers have concluded.1
Moreover, patients diagnosed with bladder cancer are in need of new treatment options. Although a role for immunotherapy has been established for non-muscle invasive UC since the approval of the Bacillus Calmette-Guérin vaccine in 1976, there were no such agents available for advanced disease until the approval of the PD-L1 inhibitor atezolizumab (Tecentriq) in May 2016. The armamentarium expanded in February with the approval of the PD-1 inhibitor nivolumab (Opdivo) for patients with advanced or metastatic UC (mUC) that has progressed during or after platinum-containing chemotherapy.
Clinical trial findings presented in recent weeks at major oncology conferences have added to the body of evidence building for these agents. The following is a summary of the latest findings.
Checkpoint Inhibitors in Action
The FDA granted atezolizumab accelerated approval as a treatment for patients with locally advanced or mUC whose disease progressed during or after platinum-based chemotherapy either before or after surgery based on the data from the phase II IMvigor 210 study. The overall response rate (ORR) in that trial was 15% among all patients and 26% among participants with PD-L1 expression ≥5% on infiltrating immune cells in the tumor microenvironment.1
In January, investigators presented data about the impact of prior therapies on outcomes with atezolizumab treatment at the 2017 Genitourinary Cancers Symposium.2
Patients with UC in the platinum-pretreated cohort of the IMvigor 210 study (NCT02108652) received 1200 mg of atezolizumab intravenously (IV) on day 1 of a 21-day cycle. Of the evaluable patients (n = 310), the median age was 66 years, and 82% of patients had received prior systemic treatment, with the lines of prior regimens ranging from 1 to 4 or more. Of those patients who received prior therapy, 73% received prior cisplatin-based chemotherapy, and 26% received carboplatin-based chemotherapy.2
Responses occurred regardless of the number of prior therapies, and were ongoing in 65% of responding patients at the data cutoff date (July 4, 2016). A clinically meaningful benefit was observed, with minimally and heavily pretreated patients experiencing durable responses (Table 1).2
Table 1. Clinical Benefit of Atezolizumab in the IMvigor 210 Study1
In a phase Ia study of the long-term impact of atezolizumab in previously treated patients with mUC (NCT01375842), atezolizumab was well tolerated without new safety signals in this patient population. The study concluded that the durability of responses, including complete response (CR) rates and an extended OS, confirm atezolizumab as a new standard therapy for previously treated patients with mUC.3
In this investigation, evaluable patients (n = 95) received 15 mg/kg or 1200 mg of atezolizumab through an IV every 3 weeks. The median age was 66 years, 76% of patients were male, 80% had primary bladder tumors, and 61% had an ECOG performance status of 1. The median treatment duration was 3 months, and 24% of patients were treated for 1 year or longer.