Roche to Withdraw US Indication for Atezolizumab in Previously Untreated Locally Advanced or Metastatic Urothelial Carcinoma

Roche is voluntarily withdrawing the United States indication for atezolizumab (Tecentriq) for the treatment of adults with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 tumor proportion score of at least 5%, or who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.¹

The drug manufacturer made decision following consultation with the FDA regarding the phase 3 IMvigor130 trial (NCT02807636). In that trial, atezolizumab plus chemotherapy did not meet the co-primary endpoint of overall survival (OS) compared with chemotherapy alone.

The confirmatory IMvigor130 trial aimed to convert the accelerated approval of atezolizumab to a regular approval. In April 2017, the FDA granted an accelerated approval to atezolizumab as a frontline treatment for cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma based on findings from the phase 2 IMvigor210 trial (NCT02108652).²

The withdrawal will not affect any other indications for atezolizumab in the United States, according to Roche.

“While we are disappointed with this withdrawal, we understand the need to uphold the principles of the US FDA’s Accelerated Approval Program, which brings innovative medicines to patients sooner. We remain confident in the benefit Tecentriq offers to people diagnosed with some of the most difficult-to-treat forms of cancer,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, stated in a press release. “There is a considerable unmet need for effective and tolerable treatments for people living with advanced bladder cancer and so we regret that the IMvigor130 trial did not cross the statistical threshold for OS.”

Investigators are scheduled to present detailed findings from IMvigor130 at an upcoming medical meeting. The multicenter, randomized, placebo-controlled trial evaluated atezolizumab alone and in combination with chemotherapy vs chemotherapy alone in patients with untreated advanced urothelial cancer.

Patients were required to be eligible to receive platinum-based chemotherapy, have measurable disease per RECIST v1.1 criteria, have an ECOG performance status of 0 to 2, and have adequate end-organ and hematologic function.³ No prior chemotherapy for inoperable locally advanced or metastatic urothelial carcinoma was permitted. Prior local intravesical chemotherapy or immunotherapy is allowed if completed at least 4 weeks prior to the initiation of study treatment.

Key exclusion criteria included any approved anticancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment; treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to enrolment, or active or untreated central nervous system metastases.

Enrolled patients were randomly assigned to intravenous (IV) atezolizumab alone at 1200 mg once every 3 weeks; the same dosing schedule of atezolizumab plus chemotherapy consisting of carboplatin at 4.5 mg/ml once every 3 weeks, gemcitabine at 1000 mg/m2 on day 1 and 8 of every 21-day cycle, and cisplatin at 70 mg/m2 once every 3 weeks; or carboplatin, gemcitabine, and cisplatin plus placebo.

The co-primary end points of the trial were OS, progression-free survival, and safety.

References

1. Roche provides update on Tecentriq US indication for previously untreated metastatic bladder cancer. News release. Roche. November 29, 2022. Accessed November 29, 2022. http://bit.ly/3Vj3JJr
2. FDA grants Genentech’s Tecentriq (atezolizumab) accelerated approval as initial treatment for certain people with advanced bladder cancer. News release. Genentech. April 17, 2017. Accessed November 29, 2022. http://bit.ly/3ENAY0t
3. Study of atezolizumab as monotherapy and in combination with platinum-based chemotherapy in participants with untreated locally advanced or metastatic urothelial carcinoma (IMvigor130). ClinicalTrials.org. Updated October 14, 2022. Accessed November 29, 2022. https://clinicaltrials.gov/ct2/show/NCT02807636