Petros Grivas, MD
Immunotherapy is likely to represent the future of bladder cancer care, especially in combinations with chemotherapy and targeted therapy regimens, according to Petros Grivas, MD.
“Recently, we had the combination of ipilimumab (Yervoy) and nivolumab (Opdivo) in patients with kidney cancer, said Grivas, a medical oncologist at the Cleveland Clinic. “The question is how this combination will go through in patients with urothelial carcinoma.”
An ongoing phase I study examining cabozantinib (Cabometyx) plus nivolumab with or without ipilimumab is currently accruing patients (NCT02496208). This study aims to the determine the safety and tolerability of a novel dose of cabozantinib, nivolumab, and ipilimumab in patients with urothelial cancer and other GU malignancies.
In an interview during the 2017 OncLive®
State of the Science on Genitourinary CancersTM
, Grivas shared insight on the value of combining immunotherapy regimens in the treatment of patients with urothelial carcinoma.
OncLive: Please provide an overview of your presentation on bladder cancer.
: I discussed the recent updates with immunotherapy, specifically immune checkpoint inhibitors, in the management of patients with advanced urothelial carcinoma. Over the last couple of years, we have seen data with 5 FDA approvals of immune checkpoint inhibitors for the management of patients with platinum-refractory advanced urothelial cancer.
Two of them have been approved in the first-line setting and they present new treatment options for those patients. I reviewed the data behind these approvals of these 5 agents. We sorted through safety, efficacy, and the level of evidence for each of those agents.
In addition, we gave a snapshot of what the treatment options are for patients with advanced urothelial cancer. We have new chemotherapy, immunotherapy, and clinical trials that consider the treatment of this current landscape. We captured some promising combination therapies as examples of what is happening in the clinical trial setting and which combinations might look promising enough to move onto phase III clinical trials.
Moreover, we are discussed some concepts of biomarkers and how these might be used in the future. We touched upon the prospect of different promising scenarios in the future in terms of looking at patient selection based on those biomarkers.
We have those 5 checkpoint inhibitors now available. What is next for the treatment landscape?
This is a great environment since there are many ongoing clinical trials…We are approaching a thousand clinical trials across tumor types evaluating different combinations of immunotherapy—either with other immunotherapy agents or chemotherapy or targeted therapy. We have a plethora of information in clinical trial designs that we are sorting through. Some interesting combinations might come through but, recently, we had the combination of ipilimumab and nivolumab explored in patients with kidney cancer. The question is how this combination will fare in patients with urothelial carcinoma.
We have 4 large clinical trials looking at combination immunotherapy or single-agent immunotherapy versus chemotherapy in the first-line setting of patients with advanced urothelial cancer. Two of those trials are testing the combinations of chemotherapy plus immune checkpoint inhibition. Moreover, we have maintenance trials in which patients after first-line chemotherapy are randomized to either immunotherapy with checkpoint inhibitors or observation or placebo depending on the trial to evaluate the concept of the maintenance approach before progression to prolong progression-free survival and overall survival.
There are multiple combinations looking at different immunotherapy compounds that target different components of the immune system. PD-1 with IDO or any other compounds are critical players of the immune system. An approach that I find interesting is the combination of targeted therapies with immunotherapy. It might have a significant role in selected patients based on the presence of genomic alterations that define patient subsets who will benefit from targeted therapy approaches.
Can you explain the synergy that exists with immunotherapy and chemotherapy and why that might be an exciting combination for the field?
Chemotherapy by itself may have the opportunity and potential to induce changes in the tumor microenvironment. We have some data from the Cleveland Clinic where we looked at tissue expression of PD-L1, PD-L2, and PD-1 with the gene expression profiling before and after neoadjuvant chemotherapy. It was mainly with cisplatin, which is the standard of care in that setting.