Expert Review on the Multidisciplinary Management of Bladder Cancer - Episode 10

Novel Therapies Needed for Muscle-Invasive Bladder Cancer

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The PD-L1 inhibitor atezolizumab (formally MPDL3280A) was granted breakthrough therapy designation from the FDA in June 2014, representing a future advance. In the study that led to this designation, the objective response rate with atezolizumab was 43% in PD-L1 positive patients (IHC 2/3). At the time of the data cutoff in 2014, 94% of patients had ongoing responses.

At this time, there are still no FDA-approved agents for the treatment of muscle-invasive bladder cancer, Dean F. Bajorin, MD, states. Combining immunotherapies and angiogenic inhibitors offers possibilities for future treatments, states moderator Daniel P. Petrylak, MD. However, these combinations also pose greater risk for toxicities, he adds.

While promising as treatments, immunotherapies can cause pseudoprogression, during which tumors increase in size but the increase is not actual disease progression. Due to the potential for pseudoprogression with these agents, Petrylak suggests that current response criteria must be reconsidered. This phenomenon, explains Bajorin, may be infiltration, partial growth, or just a delay in the immune system responding to the antigens. Evan Y. Yu, MD, notes that current clinical trials evaluating checkpoint inhibitors have accounted for the potential of pseudoprogression, and individuals may be treated beyond initial progression in these trial designs.