Monika Joshi, MD, associate professor, Division of Hematology/Oncology, Penn State Hershey Medical Center, discusses the rationale for using durvalumab (Imfinzi) in combination with radiation therapy (RT) in patients with localized urothelial carcinoma.

The phase Ib DUART/BTCRC-GU15-023 study evaluated the safety of combining durvalumab with RT followed by adjuvant durvalumab in patients with urothelial carcinoma. 

The trial enrolled patients who were either surgically unresectable, unfit for surgery, or cisplatin-ineligible, says Joshi. While the study included patients with localized disease, patients who were node positive with N1 or N2 disease were eligible for enrollment.

In 2017, the FDA approved durvalumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemotherapy in the neoadjuvant or adjuvant setting.

RT is also a useful modality for patients with localized bladder cancer, says Joshi.

The goal of the study is to define newer treatment approaches for patients with nonmetastatic disease, concludes Joshi.

Videos

Monika Joshi, MD, discusses the rationale for using durvalumab in combination with radiation therapy in patients with localized urothelial carcinoma.

Dr. Joshi on Rationale for Durvalumab/RT Combo in Localized Urothelial Carcinoma

Monika Joshi, MD, associate professor, Division of Hematology/Oncology, Penn State Hershey Medical Center, discusses durvalumab (Imfinzi) and radiation therapy (DUART) in locally advanced urothelial cancer of the bladder.

This type of regimen has been studied in the preclinical setting, as well as the clinical setting. For example, the PACIFIC study treated patients with stage III non—small cell lung cancer with durvalumab following concurrent chemoradiation. This trial inspired the phase I/II DUART/BTCRC-GU15-023 study in patients with urothelial cancer of the bladder, Joshi explains.

Radiation primes the immune system and causes more DNA damage to cancer cells. It also causes an increase in antigen presentation, which leads to a pro-inflammatory environment. When immunotherapy and radiation therapy are combined, the hypothesis of the study was that this environment would increase response rates and patients would have improved clinical outcomes, concludes Joshi.

Monika Joshi, MD, discusses durvalumab (Imfinzi) and radiation therapy (DUART) in locally advanced urothelial cancer of the bladder.

Dr. Joshi on Durvalumab/RT Combo in Locally Advanced Urothelial Cancer

Monika Joshi, MD, assistant professor, Penn State Hershey Medical Center, discusses a phase Ib study of durvalumab (Imfinzi) and radiation therapy (DUART) followed by adjuvant durvalumab in patients with urothelial carcinoma during the 2018 Genitourinary Cancers Symposium.

There are no existing safety data for the combination of a PD-L1 agent like durvalumab with radiation therapy, Joshi explains. Therefore, this single-arm study aimed to examine the safety signal when combining these 2 modalities. The study will now be expanded to a phase II trial looking at efficacy, with a primary endpoint of median progression-free survival (PFS) and disease control rate.

In the phase Ib portion of the study, presented during the symposium, a total of 6 patients were treated with the combination of durvalumab and radiation therapy on day 1 and day 28 of a 7-week period. Joshi says investigators did not see any clinically significant immune-related adverse events, which was very encouraging. 

The majority of patients experienced lymphopenia or thrombocytopenia and non-infective cystitis, but it is fair to conclude that this combination is safe and tolerable, she notes.

Monika Joshi, MD, assistant professor, Penn State Hershey Medical Center, discusses a phase Ib study of durvalumab (Imfinzi) and radiation therapy (DUART) followed by adjuvant durvalumab in patients with urothelial carcinoma.

Monika Joshi, MD

Articles

Dr. Joshi on Rationale for Durvalumab/RT Combo in Localized Urothelial Carcinoma

Dr. Joshi on Durvalumab/RT Combo in Locally Advanced Urothelial Cancer

Dr. Joshi Discusses Durvalumab and Radiation Therapy in Bladder Cancer