Genentech Withdraws Atezolizumab Indication for Certain Patients with Metastatic Bladder Cancer

Roche has voluntarily withdrawn the US indication of atezolizumab (Tecentriq) for the treatment of adults with advanced or metastatic urothelial carcinoma (mUC), according to a press release from Genentech.¹

The indication was for patients with mUC who are not eligible for cisplatin chemotherapy, had a PD-L1 expression, or were not eligible for any platinum-based chemotherapy regardless of their PD-L1 status. The decision was made to remove atezolizumab’s indication for this patient population after the phase 3 IMvigor130 trial (NCT02807636) failed to reach its co-primary end point of overall survival (OS) when comparing atezolizumab plus chemotherapy to chemotherapy alone in patients with mUC.

The results of the trial was the designated post-marketing requirement for Genentech to convert its accelerated approval of atezolizumab to a regular approval but failing to meet this requirement led to the decision to remove the indication after consulting the FDA. According to Genentech, the phase 3 data that show’s how atezolizumab missed it’s end point will be shown at a later conference.

“While we are disappointed with this withdrawal, we understand the need to uphold the principles of the 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,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech in a press release.

Early results from the IMvigor130 trial suggested that the addition of atezolizumab to platinum-based chemotherapy prolonged progression-free survival (PFS) for patients with mUC and that the safety profile was consistent with the treatments as individual agents.² However, OS data was not significant at the time.

At the time of final PFS analysis in 2019 the median PFS in the intent to treat population was 8·2 months (95% CI, 6.5–8.3) in the group of patients on the combination therapy (n = 362) compared with the placebo and chemotherapy group (n = 400) at 6.3 months (95% CI, 6.2-7.0) with a hazard ratio (HR) of 0.82 (95% CI, 0.70–0.96, P = 0.007). Moreover, median OS between atezolizumab plus chemotherapy vs placebo and chemotherapy was 15.7 months (95% CI, 13.1-17.8) vs 13.4 months (95% CI, 11.7-15.1), respectively (HR 0.83; 95% CI, 0.69–1.00, P = 0.027).

The treatment remained tolerable with adverse events (AEs) that led to withdrawal in 156 (43%) patients on the combination therapy and 11% had AEs that led to discontinuation of atezolizumab. The most common grade 3 or 4 AEs related to atezolizumab, or placebo were neutropenia, anemia, decreased platelets, decreased neutrophils, and thrombocytopenia.

“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 overall survival,” Garraway added.

Genentech has had to already remove atezolizumab’s indication for patients with mUC who had prior treatment with platinum chemotherapy.3 Atezolizumab had been given accelerated approval based of the phase 2 IMvigor210 study (NCT02108652) but was contingent on results of the IMvigor211 study (NCT03620435) that had missed its primary end point of OS in patients with a high expression of PD-L1.

According to the manufacturer, this decision will not affect the other disease indications for atezolizumab, and they recommend that patients on the monoclonal antibody to reach out to their healthcare provider to discuss next steps.

_References

_{1. Genentech Provides Update on Tecentriq U.S. Indication for Previously Untreated Metastatic Bladder Cancer. News Release. November 28, 2022. Accessed: November 29th, 2022. https://bit.ly/3u7xT6D}

_{2. Galsky MD, Arija JÁA, Bamias A, et al; IMvigor130 Study Group. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicenter, randomized, placebo-controlled phase 3 trial. Lancet. 2020 May 16;395(10236):1547-1557. doi: 10.1016/S0140-6736(20)30230-0}

_{3. Roche provides update on Tecentriq US indication in prior-platinum treated metastatic bladder cancer. News Release. March 8, 2021. Accessed: November 29, 2022. shorturl.at/dkpA5}