Exploring the Role of Chemotherapy and Immunotherapy Combos in Urothelial Carcinoma

Danielle Bucco
Published: Thursday, Oct 05, 2017

Andrea Necchi
Andrea Necchi
Immunotherapy regimens may present the future of bladder cancer, particularly in combination with chemotherapy, according to Andrea Necchi, MD.

“PD-1/PD-L1 immune checkpoint inhibitors have already been approved in the United States and Europe for patients with metastatic urothelial cancer who have failed platinum-based chemotherapy or who are ineligible to receive cisplatin-based chemotherapy. This has given an option to those patients who might benefit from them,” states Necchi.

For example, pembrolizumab (Keytruda) significantly improved overall survival over investigators’ choice of chemotherapy in patients with recurrent advanced urothelial carcinoma, according to results of the Keyote-045 study.

In an interview with OncLive at the 2017 Global Congress on Bladder Cancer, Necchi, Fondazione IRCCS Istituto Nazionale dei Tumori, in Milan, Italy, discusses the current role of immunotherapy and chemotherapy for patients with muscle-invasive bladder cancer.

OncLive: Can you please provide an overview of your presentation?

Necchi: We are here at the Global Congress on Bladder Cancer discussing the role of immunotherapy in bladder cancer and comparing immunotherapy to chemotherapy in the neoadjuvant or preoperative setting for patients with muscle-invasive bladder cancer. It is a relatively new field that we are still investigating.

PD-1/PD-L1 immune checkpoint inhibitors have already been approved in the United States and Europe for patients with metastatic urothelial cancer who have failed platinum-based chemotherapy or who are ineligible to receive cisplatin-based chemotherapy. This has given an option to those patients who might benefit from them.

There is evidence of pembrolizumab being compared to chemotherapy in the second-line setting. As a natural evolution of the oncology field across solid tumors, we are moving towards early disease stages. There are many trials that are already running in Europe, as well as the United States, that are enrolling patients with earlier disease stages. Patients with non-muscle invasive disease, bacillus Calmette-Guérin-refractory disease, or even gemcitabine resistance are being investigated in studies of combinations of immunotherapy.

There are trials that are moving on in the adjuvant space after radical cystectomy for muscle invasive tumors. There are at least 3 big randomized studies that are now comparing an immunotherapy of either atezolizumab (Tecentriq), nivolumab (Opdivo), or pembrolizumab after radical cystectomy for high-risk patients, such as patients with a nodal environment after radical cystectomy and neoadjuvant chemotherapy.

Another important focus should be on the role of immunotherapy in the neoadjuvant space. Neoadjuvant chemotherapy is included in the recommendation that is currently used by urologists and medical oncologists. It is a standard of care for patients with muscle invasive bladder cancer to receive cisplatin-based chemotherapy. Despite this data, only 20% to 30% of patients can ultimately receive neoadjuvant chemotherapy for a number of reasons. This has to do with a lot of issues that date back decades ago with separate trials conducted by urologists and medical oncologists.

Systemic chemotherapy improved overall survival compared to cystectomy alone. We are dealing with 6% to 10% of improvement in survival and fewer relapses for patients receiving systemic therapy.

There is the possibility to move the field of immunotherapy forward. There are at least 2 studies running in Europe and other studies running in the United States with immunotherapy in the neoadjuvant space. The first study is running in Milan with pembrolizumab, which includes patients with cisplatin-eligible or -ineligible disease who can receive immunotherapy rather than chemotherapy as a neoadjuvant treatment before cystectomy. 

The other study focused on the cisplatin-ineligible population. This study is investigating atezolizumab before a radical cystectomy. The results of this study can provide good evidence to move immunotherapy forward even in this setting. What we are missing is a big phase III study in the neoadjuvant setting combining immunotherapy with cisplatin-based chemotherapy, but that will be the natural next step towards the clinical trials designed in this disease. 

In the preoperative space, there are a lot of unanswered questions that deal with the safety of the administration of immunotherapy before cystectomy. We don't yet know the answer. There is also a lack of data in the literature regarding the surgical safety of major surgery after immune-checkpoint inhibitors. 


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TitleExpiration DateCME Credits
Community Practice Connections™: New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of ImmunotherapyAug 13, 20191.5
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