A new phase I trial with a compound targeting the immunosuppressive protein PDL1 shows promising results with a good toxicity profile. This provides a potentially new class of drugs for otherwise difficult-to-treat metastatic bladder cancer.
(ag) Regarding treatment of metastatic urothelial bladder carcinoma (UBC), there has been little to report over the past 30 years. Prognosis is poor and few therapies are available (chemotherapy remains standard). For patients in whom chemotherapy is ineffective or poorly tolerated, the picture looks even bleaker [1].
Due to the expression of PDL1 in the tumor microenvironment, certain forms of UBC bypass the immune response, and therefore antibodies in this area may be useful [2].
Good side effect profile
A recently published phase I study [3] investigated the anti-PDL1 antibody MPDL3280A in the treatment of metastatic refractory UBC. This intravenously administered agent blocks the interaction between PDL1 and the receptor PD1 and the marker B7.1. In the study, MPDL3280A was shown to have remarkable activity. Treatment responses in the 68 patients studied were assessed with RECIST. For the most part, they occurred rapidly (at six weeks, 43% in the group with PDL1-positive bladder cancer showed tumor shrinkage) and outlasted the time of the data cutoff.
The side effect profile was good. Of particular note is the lack of renal toxicity of the drug. This is of great importance because many patients with UBC are older and have a higher incidence of renal dysfunction. So here MPDL3280A might be more tolerable than chemotherapy.
Due to the impressive results, the drug received the so-called “breakthrough designation status” from the FDA.
Literature:
- Choueiri TK, et al. : Double-blind, randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum-pretreated metastatic urothelial cancer. J Clin Oncol 2012; 30: 507-512.
- Chen DS, Irving BA, Hodi FS: Molecular pathways: next-generation immunotherapy-inhibiting programmed death-ligand 1 and programmed death-1. Clin Cancer Res 2012 Dec 15; 18(24): 6580-6587.
- Powles T, et al: MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 2014; 558-563. doi: 10.1038/nature13904.
InFo ONCOLOGY & HEMATOLOGY 2015; 3(1): 2.
