An upcoming FDA decision for the PD-L1 inhibitor atezolizumab as a treatment for patients with bladder cancer could set the stage for an onslaught of new and highly effective immuno-oncology agents, according to Daniel Petrylak, MD.
New York GU™: 9th Annual Interdisciplinary Prostate Cancer Congress®and other Genitourinary Malignancies.
“There's never been a second-line agent approved by the FDA for metastatic urothelial carcinoma. This will open up a series of new treatments that were not available in the past,” said Petrylak, professor of medicine and medical oncology, director of prostate and genitourinary medical oncology, Yale Cancer Center. “Previously, the survival for this disease was about 9 months, and certainly with drugs like atezolizumab, we will see improvement in survival.”
Based on data from the phase II IMvigor 210 trial, the FDA granted atezolizumab a priority review as a treatment for patients with locally advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy in the metastatic setting, or whose disease worsened within 12 months of receiving platinum-based chemotherapy before or after surgery. Under the expedited priority review program, the FDA will make its approval decision by September 12, 2016.
In the IMvigor 210 trial, 310 patients received atezolizumab. PD-L1 expression was determined by infiltrating immune cells (ICs) in the tumor microenvironment and was defined by the percentage of PD-L1positive immune cells. Patients were identified as IC0 (<1%), IC1 (≥1% but <5%), and IC2/3 (≥5%).
Treatment with atezolizumab resulted in a significantly improved overall response rate (ORR) for each IC group compared with a historical control, with a 27% ORR in the IC2/3 group (95% CI, 19-37;P<.0001), 18% ORR in the IC 1/2/3 group (95% CI, 13-24;P= .0004), and a 15% ORR in all patients (95% CI, 11-20;P= .0058). The historical ORR in the second-line setting is 10%.
With longer follow-up data by independent review, ORRs were 26% (95% CI, 18-36) in the IC2/3 group, 18% (95% CI, 13-24) in the IC1/2/3 group, and 15% (95% CI, 11-19) overall in all 310 patients. At a median follow-up of 11.7 months (95% CI, 11.4-12.2), ongoing responses were recorded in 38 (84%) of 45 responders.
Fatigue was the most common grade 3/4 treatment-related adverse events (AEs), occurring in 50 of 310 treated patients (16%). Grade 3/4 immune-mediated AEs occurred in 15 patients (5%), with pneumonitis, increased aspartate aminotransferase, increased alanine aminotransferase, rash, and dyspnea being the most common. No treatment-related deaths occurred during the study.
“Immune therapy is very well tolerated, but there are some side effects you have to watch out for, such as transaminitis, skin rash, lung diseaseyou've got to look out for these issues,” said Petrylak. “The patients that are not suited for immune therapy are the patients that have autoimmune diseases, such as psoriasis that requires medical intervention or other immune diseases.”
Several studies hope to build on these early results. The confirmatory study for the IMvigor 210 study is the phase III IMvigor211 study, which is comparing atezolizumab with investigator's choice of paclitaxel, docetaxel, or vinflunine for patients with urothelial bladder cancer following a prior platinum-containing regimen. The primary endpoint of this study, which has fully accrued patients, is overall survival (NCT02302807).
“We've never had an immune agent approved for metastatic disease before, so this will incorporate that into the second-line of treatment for bladder cancer and move it up earlier in this disease,” said Petrylak. “There are also studies that are looking at randomizing chemotherapy versus immune therapy in the first-line. So there are a lot of different studies that are in the immunotherapy area that are going to be accruing within the next couple of years.”