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Intravenous (IV) atezolizumab (Tecentriq, Genentech) is once again approved for bladder cancer.

Following priority review, the FDA approved both IV atezolizumab and the newer subcutaneous formulation of atezolizumab with hyaluronidase-tqjs (Tecentriq Hybreza, Genentech) as adjuvant treatments for certain patients with muscle-invasive bladder cancer (MIBC).

Specifically, the agents are approved for patients with circulating tumor DNA molecular residual disease (ctDNA MRD) after cystectomy as determined by an FDA-authorized test, according to the approval notice.

Signatera CDx (Natera), a companion diagnostic device to select patients eligible for treatment with atezolizumab or atezolizumab and hyaluronidase-tqjs also earned an FDA nod.

The approvals were based on findings from the randomized, placebo-controlled IMvigor011 trial demonstrating improved survival outcomes with atezolizumab vs placebo. Study participants were patients with MIBC who had radical cystectomy with lymph node dissection and who were determined to have ctDNA MRD during the subsequent 12 months. 

Median disease-free survival was 9.9 months vs 4.8 months among the 250 patients randomized 2:1 to receive 1680 mg of atezolizumab or placebo, respectively (hazard ratio [HR], 0.64). Treatment was given every 4 weeks for up to 12 cycles or 1 year (whichever occurred first) unless there was recurrence or unacceptable toxicity. 

Overall survival was also significantly better in the atezolizumab arm (median of 32.8 vs 21.1 months with placebo; HR, 0.59).

The recommended dose of atezolizumab is 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks unless there is disease recurrence or unacceptable toxicity. For atezolizumab and hyaluronidase-tqjs — which was approved in 2024 for all FDA-approved indications for IV atezolizumab — the dose is 1875 mg of atezolizumab and 30,000 units of hyaluronidase every 3 weeks for up to 1 year, unless there is disease recurrence or unacceptable toxicity.

Prescribing information, which will be posted on Drugs@FDA, includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity. 

“Patients with negative Signatera CDx test results should continue with serial testing until a positive test result or completion of the recommended 12-month testing window,” the FDA stated.

Of note, IV atezolizumab, which is currently approved for multiple cancer indications, was initially granted accelerated approvals for some patients with urothelial carcinoma — a certain type of bladder cancer — in 2016 based on findings from IMvigor210. However, Genentech voluntarily withdrew one indication when the confirmatory phase 3 IMvigor211 trial failed to meet its primary endpoint. 

Similarly, the company withdrew a second indication in 2022 when the IMvigor130 trial failed to meet its co-primary endpoint of overall survival with atezolizumab plus chemotherapy vs chemotherapy alone.

The new approval is based on a different treatment approach. 

The IMvigor011 study, on which the latest FDA approval is based, is “the first prospective Phase III study to demonstrate that a ctDNA-guided approach to adjuvant therapy can significantly improve survival in MIBC,” Genentech stated in a press release.

“For the patients and families, the ‘watch and wait’ period after a cystectomy is often defined by uncertainty. This ctDNA-guided approach can enable doctors to use serial ctDNA MRD testing to identify who is at a higher risk of recurrence and move quickly toward immunotherapy for those who may benefit from it, while allowing others to safely avoid additional treatment and its associated side effects,” Meri-Margaret Deoudes, CEO of the Bladder Cancer Advocacy Network, stated in the Genentech press release.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDEdge and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on X: @SW_MedReporter.