FDA panel: atezolizumab, pembrolizumab should retain frontline bladder cancer approvals

In 2 separate votes, the FDA’s Oncologic Drugs Advisory Committee (ODAC) recommended that the immunotherapies atezolizumab (Tecentriq) and pembrolizumab (Keytruda) maintain their accelerated approvals for the frontline treatment of patients with metastatic bladder cancer.

The FDA accelerated approval program is intended to expedite the approval of drugs that meet an unmet medical need using surrogate end points as the supporting data. To continue the approval, data from a confirmatory trial must eventually be provided by the developer of the drug.

After recent negative readouts on several confirmatory trials, the ODAC panel was tasked with reviewing 6 accelerated approvals. Now that ODAC has made its positive recommendations on the atezolizumab and pembrolizumab frontline bladder cancer indications, the FDA will make its final decision on whether those accelerated approvals will continue.


The PD-L1 inhibitor atezolizumab received an accelerated approval from the FDA in May 2016 for use in patients with locally advanced or metastatic urothelial carcinoma (mUC) previously treated with platinum-based chemotherapy.1 The approval was based on objective response rate data from the phase 2 IMvigor210 study. Objective response rate data from a separate cohort of patients from the IMvigor210 study led to the April 2017 FDA accelerated approval of atezolizumab as a frontline treatment for cisplatin-ineligible patients with locally advanced or mUC.

In 2018, the FDA updated the label for frontline atezolizumab in this setting, with the approval now being specifically for patients who are not eligible for cisplatin-containing chemotherapy, and whose tumors have a PD-L1 expression level ≥5%, as determined by an FDA-approved test, or patients who are not eligible for any platinum-containing therapy, regardless of level of tumor PD-L1 expression.2

The label update was based on findings from the phase 3 IMvigor130 study indicating that these patients would benefit most from frontline atezolizumab monotherapy. The IMvigor130 study, which is the designated postmarketing requirement study for atezolizumab’s frontline indication, randomized patients with locally advanced or mUC to atezolizumab monotherapy, atezolizumab plus platinum-based chemotherapy, or placebo plus platinum-based chemotherapy. The study met one of its coprimary endpoints of progression-free survival (PFS), but final data for the other primary end point of overall survival (OS) are not yet available.

In May 2017, Roche (Genentech), the manufacturer of atezolizumab, reported that the phase 3 confirmatory IMvigor211 study exploring atezolizumab in the second-line setting for patients with locally advanced or mUC missed its primary end point of improving OS.3 Following these negative results, Roche took action in March 2021 by voluntarily withdrawing the FDA indication for the second-line use of atezolizumab in patients with locally advanced or mUC previously treated with platinum-based chemotherapy.4

This left the frontline indication, which the ODAC panel considered in its review. Based on all of the available data, the panel voted 10-1 in favor of maintaining the accelerated approval of frontline atezolizumab in locally advanced or mUC.

“Today’s positive vote reaffirms that Tecentriq fills a significant unmet need for people with previously untreated metastatic bladder cancer, many of whom cannot tolerate standard of care chemotherapy and need additional options,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, Roche, stated in a press release issued on the day of the ODAC vote.1


In May 2017, the FDA approved the PD-1 inhibitor pembrolizumab for the first-line treatment of patients with locally advanced or mUC who are ineligible for cisplatin-containing chemotherapy.

In 2018, the FDA updated the label for frontline pembrolizumab in this setting, with the approval now being specifically for the treatment of patients with locally advanced or mUC who are not eligible for cisplatin-containing therapy and whose tumors express PD-L1 (combined positive score ≥ 10), or the treatment of patients who are not eligible for any platinum-containing chemotherapy, regardless of PD-L1 status.2

The label update was based on analyses from the phase 3 KEYNOTE-361 trial, which was intended to be the confirmatory trial for the frontline accelerated approval of pembrolizumab in bladder cancer.5 The trial randomized patients with advanced or mUC to frontline treatment with single-agent pembrolizumab, pembrolizumab plus chemotherapy, or chemotherapy alone.

The results showed that adding pembrolizumab to chemotherapy did not lead to a statistically significant improvement in OS or PFS. Although there was a numerical improvement in OS and PFS with the combination versus standard chemotherapy, the difference did not achieve the threshold for statistical significance established in the trial design. Since the primary OS or PFS end points were not met with the combination, the study design did not allow for formal testing of the monotherapy arm.

Despite the KEYNOTE-361 setback, a nearly split ODAC panel voted 5 to 3 in support of maintaining the accelerated approval of pembrolizumab in this setting, concluding that the treatment still meets an unmet medical need for certain patients with bladder cancer. Panel members hope that the results of ongoing trials of pembrolizumab in bladder cancer will provide the confirmatory support needed for this accelerated approval.


1. FDA Advisory Committee Votes in Favor of Maintaining Accelerated Approval of Genentech’s Tecentriq for Previously Untreated Metastatic Bladder Cancer. Published online April 28, 2021. Accessed May 4, 2021. https://bit.ly/3vHpW6R.

2. FDA limits the use of Tecentriq and Keytruda for some urothelial cancer patients. Published online July 5, 2018. Accessed May 4, 2021. https://bit.ly/3ej3xac.

3. Roche provides update on phase III study of TECENTRIQ® (atezolizumab) in people with previously treated advanced bladder cancer. Posted online May 10, 2017. Accessed May 4, 2021. https://www.roche.com/media/releases/med-cor-2017-05-10.htm.

4. Roche provides update on Tecentriq US indication in prior-platinum treated metastatic bladder cancer. Posted online March 8, 2021. Accessed May 4, 2021. https://www.roche.com/media/releases/med-cor-2021-03-08.htm.

5. Merck Provides Update on Phase 3 KEYNOTE-361 Trial Evaluating KEYTRUDA® (pembrolizumab) as Monotherapy and in Combination with Chemotherapy in Patients with Advanced or Metastatic Urothelial Carcinoma. Published June 10, 2020. https://bit.ly/3cQzLWe. Accessed May 4, 2021.