San Francisco, CA USA (UroToday.com) A major theme of this year’s Genitourinary Symposium has been improved survival seen in advanced urothelial carcinoma with the use of immunotherapy. In this session, Dr. Galsky described the results for a phase II trial of chemotherapy + cytotoxic T-lymphocyte associated protein 4 (CTLA4) blockade for patients with metastatic urothelial carcinoma. The authors hypothesized that chemotherapy for urothelial bladder carcinoma may lead to “autovaccination” (i.e. tumor cell kill and release of tumor antigen) and other immunomodulatory effects, which could subsequently be exploited with the addition of CTLA4 blockade with ipilimumab.
Eligible patients had chemotherapy-naïve urothelial carcinoma or had completed perioperative chemotherapy more than 12 months prior to enrollment. The primary endpoint was 1-year overall survival (OS) rate. Secondary endpoints included safety, response rate, and progression-free survival (PFS). Exploratory endpoints included the immunomodulatory effects of gemcitabine and cisplatin (GC) alone and GC + ipilimumab.
Patients underwent two cycles of GC alone followed by four cycles of gemcitabine, cisplatin, and ipilimumab. Whole blood was analyzed at 3 time points for immunophenotyping of innate and adaptive immune cells and their activation status by polychromatic flow cytometry. Plasma collected at the same time points was assayed for 41 cytokines/chemokines.
A total of 36 patients were included in the study. The median age of the patient population was 60 years with 81% (29) male patients. The primary tumor site was bladder in 78% (28) of the patients. The overall response rate was 64% with a median OS of 14.6 months. This did not meet the primary endpoint. One-year OS was 59% and 6/26 (17%) had improved response after ipilimuab was added. Grade 1-2 toxicities ranged from 3-64% (fatigue most common) and Grade 3-4 toxicities ranged from 0-36% (neutropenia most common). The addition of ipilimumab increased the proportion of CD4 and CD8 T cells without depleting T regulatory or myeloid-derived suppressor cells.
The authors concluded that GC + CTLA-4 blockade is feasible. The response rate and OS were similar to historical controls. Importantly, the primary endpoint was not met. Patients who are outliers are a focus of ongoing translational work. This was the first trial initiated and reported exploring immune checkpoint blockade in metastatic urothelial carcinoma. Ongoing studies are needed to refine use of immune checkpoint blockade in this disease process.
Presented By:
Dr. Matt D. Galsky, MD
Reported By:
Benjamin T. Ristau, MD, at the 2016 Genitourinary Cancers Symposium - January 7 - 9, 2016 – San Francisco, CA
Fox Chase Cancer Center, Philadelphia, PA