Duke Health Referring Physicians


New First-Line Sequential Chemo-immunotherapy Treatment for Metastatic Urothelial Carcinoma

Avelumab to be used immediately after chemotherapy

Bladder cancer

Data from the JAVELIN Bladder 100 Trial published in September 2020 in the New England Journal of Medicine prove a survival benefit for patients who received the protein programmed death-ligand 1 (PD-L1) inhibitor avelumab after a response to a course of platinum-based chemotherapy.

The sequential chemo-immunotherapy approach is now guideline-approved by the National Comprehensive Cancer Network (category 1) following FDA approval of avelumab for the maintenance treatment of patients with locally advanced or metastatic bladder cancer that has not progressed with first-line platinum-based chemotherapy.

Duke genitourinary oncologists are finding the benefit of chemo-immunotherapy for patients with bladder cancer based on this study as well as several other ongoing trials that have had interim results. The Duke genitourinary oncology team is integrating avelumab into patient treatment plans immediately after a patient’s tumor is found to have stability or response to three to six cycles of platinum-based chemotherapy, rather than waiting until disease recurrence.

Avelumab is a fully human monoclonal antibody that targets PD-L1 and was originally developed for the treatment of non-small cell lung carcinoma. The JAVELIN Bladder 100 study—a large, global phase 3, randomized trial in patients on first line therapy for metastatic bladder cancer—found that a sequential chemo-immunotherapy approach is important for maximizing survival without sacrificing additional side effects when rotating quickly from platinum-based  chemotherapy to avelumab.

“Compared with the control population, which completed the initial phase of first-line chemotherapy and then went on to routine restaging surveillance, the intervention group that sequenced immediately to avelumab had a 12% absolute-percentage-point advantage of surviving to the first year,” says Christopher Hoimes, DO, who recently joined the genitourinary oncology program at Duke Cancer Institute as a clinical investigator with a focus on genitourinary cancers and experimental therapeutics through early-phase trials.

“The benefit was seen regardless of PD-L1 status of the tumor, though results in the PD-L1- positive group were no worse and perhaps slightly better,” adds Hoimes. “The results from the JAVELIN Bladder 100 study are practice-changing for us to maintain the responses that chemotherapy provides for metastatic urothelial cancer.”

Hoimes notes that this is one of the first studies since platinum-based chemotherapy to demonstrate extended overall survival for patients with metastatic urothelial cancer. “This study found a 31% reduction in the risk of death by sequencing chemo-immunotherapy as a first-line treatment, compared to following a maximal response with a treatment break after chemotherapy,” he says.

The Duke genitourinary oncology team is now discussing first-line treatment of sequential platinum chemotherapy for at least three cycles, followed by rotation to avelumab for patients who have response (stable disease or better) to chemotherapy. “By adapting clinical trial results early into our practice, we improve access to life-prolonging treatments for our patients,” Hoimes adds.