AstraZeneca Withdraws Durvalumab Indication for Previously Treated Locally Advanced or Metastatic Bladder Cancer

Continued approval for durvalumab in previously treated adult patients with locally advanced or metastatic bladder cancer was dependent upon results from the phase 3 DANUBE trial in the first-line metastatic bladder cancer setting, which did not meet its primary end points in 2020.

AstraZeneca announced it has voluntarily withdrawn the indication for durvalumab (Imfinzi) in previously treated adult patients with locally advanced or metastatic bladder cancer in the United States.1

Health care providers are currently being notified of this update and patients with metastatic bladder cancer being treated with durvalumab should consult with their individual provider regarding their care moving forward.

Importantly, this decision was made in consultation with the FDA and the withdrawal is aligned with FDA guidance for evaluating indications with accelerated approvals that did not meet post-marketing requirements, as part of a broader industry-wide evaluation. However, this withdrawal does not affect indications outside the United States and does not impact other approved indications for durvalumab within or outside the United States.

“The science of immunotherapy has moved swiftly over the past few years, bringing new options to patients at an unprecedented pace. While the withdrawal in previously treated metastatic bladder cancer is disappointing, we respect the principles FDA set out when the accelerated approval pathway was founded and remain committed to bringing new and innovative options to patients,” Dave Fredrickson, executive vice president of the Oncology Business Unit at AstraZeneca, said in a press release.

Durvalumab was granted accelerated approval in the United States in May 2017 based on promising tumor response rates and duration of response data observed in the phase 1/2 Study 1108 (NCT01693562). This study evaluated the safety and efficacy of durvalumab in advanced solid tumors, including previously treated bladder cancer.

However, continued approval was dependent upon results from the phase 3 DANUBE trial (NCT02516241) in the first-line metastatic bladder cancer setting, which did not meet its primary end points in 2020.

In the randomized, open-label, multicenter, global trial, investigators compared durvalumab monotherapy or durvalumab plus tremelimumab versus gemcitabine plus either cisplatin or carboplatin for the first-line treatment of both cisplatin-eligible and -ineligible patients with unresectable, metastatic urothelial cancer.2,3 Eligible patients included those with transitional cell carcinoma of the urothelium, including renal pelvis, ureters, urinary bladder, and urethra.

The primary end points of the trial were overall survival (OS) in patients with high PD-L1 treated with durvalumab monotherapy and in patients treated with durvalumab plus tremelimumab, regardless of their PD-L1 status.

Ultimately, median OS was not deemed to be significantly durvalumab and chemotherapy in patients with high PD-L1 expression nor with durvalumab plus tremelimumab and versus chemotherapy in the intent-to-treat patient population. Notably though, the safety and tolerability profiles of durvalumab and the combination with tremelimumab were consistent with previous trials.

Currently, durvalumab is approved in the curative-intent setting of unresectable, stage III non–small cell lung cancer (NSCLC) following chemoradiation therapy in the United States, Japan, China, across the European Union, and in many other countries, based on results of the phase 3 PACIFIC trial (NCT02125461). The human monoclonal antibody is also approved in the European Union, United States, Japan, and many other countries globally for the treatment of extensive-stage small cell lung cancer (ES-SCLC) based on the phase 3 CASPIAN trial (NCT03043872). Moreover, durvalumab is approved for previously treated patients with advanced bladder cancer in several countries.

Durvalumab is also being tested as part of a broad clinical program as a monotherapy and in combinations including with tremelimumab as a treatment for patients with NSCLC, SCLC, bladder cancer, liver cancer, biliary tract cancer, esophageal cancer, gastric and gastroesophageal cancer, cervical cancer, ovarian cancer, endometrial cancer, and other solid tumors. In addition, AstraZeneca has several phase 3 trials in the bladder cancer setting testing durvalumab in various treatment combinations across early- and late-stage settings including the phase 3 NILE trial (NCT03682068) in metastatic disease, the phase 3 NIAGARA trial (NCT03732677) in muscle invasive disease, and the phase 3 POTOMAC trial (NCT03528694) in non-muscle invasive disease.


1. Voluntary withdrawal of Imfinzi indication in advanced bladder cancer in the US. News release. AstraZeneca. Published February 22, 2021. Accessed February 22, 2021.

2. Powles TB, van der Heijden MS, Castellano Guana D, et al. A phase III, randomized, open-label study of first-line durvalumab (D) with or without tremelimumab (T) vs standard of care chemotherapy in patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE). Annals of Oncology. 2020;31(suppl_4):S550-S550. doi: 10.1016/annonc/annonc274

3. Update on Phase III DANUBE trial for Imfinzi and tremelimumab in unresectable, Stage IV bladder cancer. News release. AstraZeneca. Published March 6, 2020. Accessed February 22, 2021.