Petros Grivas, MD, PhD
For patients with locally advanced or metastatic bladder cancer who are cisplatin-ineligible, treatment options are limited, making clinical trials invaluable to further developments, explained Petros Grivas, MD, PhD.
“[There is a lot of potential with] combinations of targeted therapies and immunotherapies, or targeted therapy alone in some cases, said Grivas. “Right now, we only have chemotherapy and single-agent checkpoint inhibition [in advanced bladder cancer]. There is definitely room for improvement. These clinical trials provide good opportunities for biomarker discovery and validation, and hopefully, for more agents to come forward for our patients with...urothelial cancer.”
In an interview during the 2018 OncLive®
State of the Science Summit™
on Genitourinary Cancers, Grivas, director, University of Washington Medicine’s Genitourinary Cancers Program, associate professor of Oncology, University of Washington, Seattle Cancer Care Alliance, discussed the rapidly evolving locally advanced and metastatic bladder cancer field.
OncLive: What has changed in the management of localized bladder cancer in recent years?
: It's an exciting era in the management of bladder cancer, and specifically, in the localized disease setting. Thus far, we have Level I evidence for cisplatin-based neoadjuvant chemotherapy before radical cystectomy and lymph node dissection. However, many patients may not be fit enough to receive cisplatin. Right now, those patients go right to the operating room to get radical cystectomy because there's no good evidence [to support the use of] carboplatin or other agents.
To try to meet this unmet need, we have designed clinical trials with immune checkpoint inhibitors. [Efficacy] is being evaluated by pathologic complete response rates (pCRs). We have data from the ABACUS trial, which was presented at the 2018 ASCO Annual Meeting by Thomas Powles, MBBS, MRCP, MD, of Barts Cancer Centre. The trial showed a 29% pCR rate in patients who received just 2 doses of atezolizumab (Tecentriq) followed by radical cystectomy. If you look at the subset of patients who have PD-L1 expression, the pCR went up to 40%.
Similar data were presented by Andrea Necchi, MD, of Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, and colleagues at the 2018 ASCO Annual Meeting and the 2018 ESMO Congress. In the trial, patients received 3 doses of pembrolizumab (Keytruda) before radical cystectomy and lymph node dissection. In all comers, the pCR was about 40%, and 50% in those with high PD-L1 expression. These data were not practice changing, but they definitely fueled enthusiasm and brought significant attention to neoadjuvant trials with immunotherapy.
We’re looking for these immunotherapy agents—especially for those who are cisplatin-ineligible—to see whether we can offer patients a new treatment down the road. [That’s assuming] these trials confirm the activity and safety of these agents. At the same time, we may be able to build upon the cisplatin backbone. There are new trials looking at cisplatin plus immunotherapy versus cisplatin-based therapy alone. That's something that will probably be looked at in the near future to try to improve outcomes for patients with localized disease.
We also have patients who come to us after receiving a radical cystectomy. They never had neoadjuvant chemotherapy, or they received it and they still had muscle-invasive residual disease. If those patients are fit for cisplatin and have PT3-4 or node-positive disease, we tend to offer them cisplatin-based adjuvant chemotherapy. However, if they cannot receive cisplatin safely, refuse it, or already received it neoadjuvantly, we have these immunotherapy trials. There are trials [currently] looking at single-agent checkpoint inhibition in the adjuvant setting after radical cystectomy and lymph node dissection.
Is bladder preservation an option for these patients?
There is a significant effort going into improving upon the data with bladder preservation. We've used concurrent chemotherapy and radiation and chemoradiation as a backbone. We have this intergroup trial with SWOG, NRG Oncology, ECOG, ACRIN, and ALLIANCE looking at chemoradiation alone or chemoradiation plus atezolizumab (Tecentriq) to see whether the combination could improve upon bladder intact disease-free survival and other endpoints. If this trial accrues well, it will give us more data on bladder preservation.