Durvalumab plus tremelimumab active as neoadjuvant bladder cancer treatment

Presurgical treatment with the PD-L1 inhibitor durvalumab and the CTLA-4 inhibitor tremelimumab showed promise in cisplatin-ineligible patients with high-risk localized bladder cancer.

Dual immune-checkpoint blockade with the PD-L1 inhibitor durvalumab (Imfinzi) and the CTLA-4 inhibitor tremelimumab showed early signs of efficacy in cisplatin-ineligible patients with high-risk localized bladder cancer, according to findings from a phase 1 trial published in Nature Medicine.1,2

Among 24 patients who received the presurgical combination and subsequent bladder removal, 37.5% (9 patients) achieved a pathologic complete response (pCR). In the 12 patients with larger tumors (stage T3-T4), the pCR rate was 42%, and half of the patients had a reduction in tumor size down to stage T1 or less.

“This study provides early evidence that neoadjuvant treatment with combination checkpoint inhibitors is feasible in a group of patients who are in need of additional treatment options,” lead study author Jianjun Gao, MD, PhD, associate professor of Genitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center, stated in a press release.1 “In this small group of patients, the combination treatment had an acceptable safety profile with encouraging activity that supports further clinical studies in this setting.”

Overall, 28 patients with high-risk localized bladder cancer who were not eligible to receive cisplatin were enrolled at MD Anderson. According to MD Anderson, characteristics of high-risk tumors include large size, variant histology, lymphovascular invasion, hydronephrosis, and/or disease located in the upper tract of the urothelium.1

Baseline characteristics showed that the median patient age was 71 years, 82% of patients were Caucasian, and 71% were men. All patients received 2 doses of the durvalumab/tremelimumab combination, with 24 patients completing surgery following the neoadjuvant treatment. The study defined pCR as no detectable evidence of cancer at the time of surgery.

Among the 24 patients who completed surgery, the 1-year median overall survival (OS) had not yet been reached, and all patients remained alive at 1 year. Also of note, at the 1-year follow-up, 82.8% of these patients were also recurrence-free.

The safety analysis included all 28 patients who received the neoadjuvant regimen. Almost all patients had immune-related adverse events across all grades, with the most frequently reported being grade 1/2 rash and grade 1/2 asymptomatic increases in amylase, both occurring in 29% of patients. Grade ≥3 immune-related adverse events occurred in 6 (21%) patients and included hepatitis and colitis. No deaths related to study treatment occurred on the trial.

The investigators also conducted biomarker analyses and observed that in the group of patients whose tumors had a higher density of tertiary lymphoid structures, the response rate was higher and OS and relapse-free survival were longer.

“Immune checkpoint therapy has clearly revolutionized cancer care with patients with metastatic disease in multiple tumor types, but we continue to work toward moving these therapies into earlier disease settings for patients in need,” corresponding author Padmanee Sharma, MD, PhD, professor of Genitourinary Medical Oncology and Immunology at MD Anderson, stated in the press release. “By combining these therapies, we felt we could take advantage of the distinct biologic mechanisms and stimulate a more robust anti-tumor immune response for these patients.


1. Dual checkpoint blockade promising as pre-surgical approach for certain patients with localized bladder cancer. Published October 12, 2020. Accessed October 12, 2020. https://bit.ly/312nefo

2. Gao, J, Navai, N, Alhalabi O, et al. Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma [published online October 12, 2020]. Nat Med. doi: 10.1038/s41591-020-1086-y