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Chemotherapy May Be Vital to Long-Term Immunotherapy Efficacy in Bladder Cancer

Caroline Seymour
Published: Wednesday, Mar 14, 2018

Parminder Singh, MD
Parminder Singh, MD
In bladder cancer, combination strategies, particularly the combination of immunotherapy and chemotherapy, are under investigation. Chemotherapy, says Parminder Singh, MD, is going to make a comeback to improve treatment efficacy.

The development of immunotherapy made physicians optimistic about moving away from chemotherapy; however, approximately 1 in 7 patients derive benefit from PD-1/PD-L1 monotherapy. In other disease settings, such as lung cancer, the combination of immunotherapy and chemotherapy is showing a benefit in patients regardless of PD-L1 expression.

“Chemotherapy is going to make a comeback as a sensitizing agent for the immune system and consequent immune therapy. It seems counterintuitive because chemotherapy is considered immuno-suppressive, but it appears that chemotherapy can make the tumor environment ‘hot,’ so that it responds to and is controlled by immunotherapy stimulus” says Singh.

In an interview during the 2018 OncLive® State of the Science Summit™ on Genitourinary Cancers, Singh, hematologist/ oncologist, Mayo Clinic, discussed the potential of immunotherapy, the importance of sequencing to avoid disease progression, and the use of chemotherapy and radiation therapy to reach an unmet need in muscle-invasive disease.

OncLive®: What is the state of immunotherapy in bladder cancer?

Singh: Immune therapy is efficacious for patients with bladder cancer, but there are potential toxicities and interactions with other medications to be aware of. 

KEYNOTE-045 showed that pembrolizumab (Keytruda) sustained its improvement in overall survival compared with chemotherapy. Is the future headed toward combination approaches or continued use of single-agent therapy?  

We already have 5 FDA-approved agents based on immune checkpoint pathways. They all have activity as single agents, but we know the activity of these agents is limited to a small group of patients. We want to expand those results to other patients who progress.

The next step is looking at combinations of immune checkpoint inhibitors in combination with newer immune checkpoint inhibitors or with chemotherapy and/or radiation. Those clinical trials are in development and are soon opening.

What patient population sees the greatest benefit from immunotherapy?

At this point, patient selection is based on the approval or labeling indications of the drug, where the patient lies in the spectrum of disease, and if they have any alternative options. Pembrolizumab and atezolizumab (Tecentriq) are both approved in first- and second-line treatment. Durvalumab (Imfinzi), nivolumab (Opdivo), and avelumab (Bavencio) are approved for cisplatin-ineligible patients who have progressed on platinum-based chemotherapy.


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