On May 15, the U.S. Food and Drug Administration (FDA) approved the PD-L1 inhbitor atezolizumab (Tecentriq) and atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) as adjuvant therapies for adults with muscle-invasive bladder cancer (MIBC) after cystectomy who have circulating tumor DNA molecular residual disease (ctDNA MRD), as determined by an FDA-authorized test.
The FDA also approved Signatera CDx (Natera, Inc.) as a companion diagnostic device for select patients with MIBC after cystectomy who have ctDNA MRD for adjuvant treatment with atezolizumab or atezolizumab and hyaluronidase-tqjs .
IMvigor011
Efficacy was evaluated in IMvigor011 (ClinicalTrials.gov identifier NCT04660344), a multicenter, randomized, double-blind, placebo-controlled trial. Researchers enrolled 250 patients with MIBC who had undergone radical cystectomy with lymph node dissection. MRD was identified by serial blood-based ctDNA monitoring performed during the 12 months after surgery, beginning at least 6 weeks after cystectomy. Patients were randomly assigned 2:1 to receive either atezolizumab at 1,680 mg or placebo intravenously every 4 weeks. Treatment continued for up to 12 cycles or 1 year, whichever occurred first, unless there was disease recurrence or unacceptable toxicity.
The major efficacy outcome measure was investigator-assessed disease-free survival; overall survival was an additional efficacy outcome measure.
A statistically significant improvement in disease-free survival was observed with atezolizumab compared to placebo, with a median of 9.9 months (95% confidence interval [CI] = 7.2–12.7 months) for atezolizumab vs 4.8 months (95% CI = 4.1–8.3 months) for placebo (hazard ratio [HR] = 0.64, 95% CI = 0.47–0.87, P = .0047). A statistically significant improvement in overall survival was also observed, with a median of 32.8 months (95% CI = 27.7 months to not estimable) and 21.1 months (95% CI = 14.7 months to not estimable) in the respective arms (HR = 0.59, 95% CI = 0.39, 0.90, P = .0131).
The prescribing information for atezolizumab and for atezolizumab and hyaluronidase-tqjs includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.
Recommended Dosage
The recommended atezolizumab dose administered intravenously is 840 mg every 2 weeks, 1,200 mg every 3 weeks, or 1,680 mg every 4 weeks for up to 1 year, unless there is disease recurrence or unacceptable toxicity. The recommended dosage of atezolizumab and hyaluronidase-tqjs is 1,875 mg of atezolizumab and 30,000 units of hyaluronidase administered subcutaneously every 3 weeks for up to 1 year, unless there is disease recurrence or unacceptable 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.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review.
