Atezolizumab’s Unresectable Locally Advanced or mTNBC Indication Withdrawn from US Market

Atezolizumab plus nab-paclitaxel will no longer be a treatment option for adult patients with unresectable locally advanced or metastatic triple-negative breast cancer following Roche's withdraw of the indication from the United States market.

Atezolizumab (Tecentriq) has been voluntarily withdrawn as a treatment option for adults with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) whose tumors express PD-L1, as determined by an FDA approved test, in combination with chemotherapy, announced Roche, in a press release.1

The atezolizumab combination was granted accelerated approval by the FDA in 2019 on the basis of promising early results from the phase 3 IMpassion130 clinical trial (NCT02425891). Progression-free survival (PFS) was prolonged with atezolizumab plus nab-paclitaxel (HR, 0.80; 95% CI, 0.69-0.92; P =.002). Further, the overall survival (OS) was longer with atezolizumab at 21.3 months compared with 17.6 months without atezolizumab (HR, 0.84; 95% CI, 0.69-1.02; P =.08).2

Final results from IMpassoin130 required a greater improvement in PFS than what was demonstrated with the combination by the end of the study.

“TNBC remains the most challenging type of breast cancer to treat, which makes the decision to withdraw so difficult for us, as patients have had this medicine as an important option for more than two years,” said Levi Garraway, MD, PhD, Roche’s chief medical officer and head of Global Product Development. “We appreciate the opportunity to have been able to help people with mTNBC in the US with Tecentriq through the accelerated approval process, which has brought many significant and novel therapies to patients. We remain dedicated to finding meaningful treatments for people living with this aggressive disease and will continue to study Tecentriq in mTNBC.”

The phase 3, multicenter, randomized, placebo-controlled include 902 patients with unresectable locally advanced or mTNBC. Patients were treated with atezolizumab 840 mg via intravenous infusion on days 1 to 15 of each 28-day cycle in combination with nab-paclitaxel 100 mg per square meter via IV infusion on days 1, 8, and 15 of each 28-day cycle. The chemotherapy arm received an equivalent dose of nab-paclitaxel. Both therapies in the study were continued until disease progression or unacceptable toxicity.2,3

At a data cutoff date of April 17, 2018, after a median follow-up of 12.9 months, the combination of atezolizumab and nab-paclitaxel achieved a 40% reduction in the risk of disease progress or death compared with nab-paclitaxel alone. The median PFS observed was 7.4 months with the addition of atezolizumab compared with 4.8 months with nab-paclitaxel only (HR, 95% CI, 0.48-0.77; P <.0001).3

Atezolizumab also led to a 33% reduction in the risk of death compared with nab-paclitaxel monotherapy (HR, 0.67; 95% CI, 0.53-0.86).

In terms of safety, the majority of most any-grade adverse events (AEs) were similar between the treatment arms. The most common grade 3/4 AEs with atezolizumab/nab-paclitaxel and nab-paclitaxel were neutropenia (8% vs 8%), decreased neutrophil count (5% vs 3%), peripheral neuropathy (6% vs 3%), fatigue (4% vs 3%), and anemia (3% vs 3%), respectively.

Withdrawal from the indication n combination with nab-paclitaxel as a treatment option for adults with unresectable locally advanced or mTNBC whose tumors express PD-L1, as determined by an FDA approved test, does not impact of indication for atezolizumab. In the next weeks, Roche plan to work with the FDA to complete the withdrawal process.

References:

1. Roche provides update on Tecentriq US indication for PD-L1-positive, metastatic triple-negative breast cancer. News release. Roche. August 27, 2021. Accessed August 27, 2021.

2. Schmid P, Adams S, Rugo HS, et al; IMpassion130 Trial Investigators. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379(22):2108-2121. doi: 10.1056/NEJMoa1809615

3. Schmid P, Rugo HS, Adams S, et al; IMpassion130 Trial Investigators.
Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21:44-5. doi: 10.1016/S1470-2045(19)30689-8