FDA Committee Supports Maintaining Accelerated Approval of Atezolizumab in PD-L1+ mTNBC

The FDA’s Oncologic Drugs Advisory Committee voted 7 to 2 in favor of atezolizumab plus nab-paclitaxel maintaining its accelerated approval to treat patients with unresectable, locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1.

The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 7 to 2 in favor of maintaining the accelerated approval granted to atezolizumab (Tecentriq) plus nab-paclitaxel (Abraxane) to treat adult patients with unresectable, locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1, as determined by an agency-approved test, according to Roche, the agent’s manufacturer.1

The FDA has not announced when it will make its final decision on this indication for atezolizumab.

The atezolizumab combination was granted accelerated approval – which allowed for conditional approval because it filled an unmet medical need for this patient population – by the FDA in March 2019. The accelerated approval was based on data from the multicenter, international, double-blind, placebo-controlled, randomized phase 3 IMpassion130 trial(NCT02425891), in which the addition of the PD-L1 inhibitor atezolizumab to nab-paclitaxel reduced the risk of progression or death by 40% compared with nab-paclitaxel alone in adult patients with unresectable, locally advanced or metastatic TNBC.2

Median progression-free survival (PFS) was 7.4 months (95% CI, 6.6-9.2) for patients receiving atezolizumab plus nab-paclitaxel, compared with 4.8 months (95% CI, 3.8-5.5) for those receiving placebo plus nab-paclitaxel (HR, 0.60; 95% CI, 0.48-0.77; P < .0001). Moreover, the objective response rate in patients with confirmed responses was 53% in the atezolizumab arm, compared with 33% in the placebo arm.

The indication earned accelerated approval based on PFS data. However, the approval was contingent upon results from the IMpassion131 trial (NCT03125902), published in Lancet Oncology in 2020, which failed to show a statistically significant PFS advantage in the intent-to-treat population (HR, 0.86; 95% CI, 0.72-1.02; P = .078).3

“As the clinically meaningful benefit demonstrated in the IMpassion130 study remains, Roche looks forward to continuing to work with the FDA to determine next steps with regard to Tecentriq in this indication,” the company stated in its release.1

The ODAC meeting was a part of an industry-wide review of 6 accelerated approvals that have undergone confirmatory trials with unmet primary end points and have not been given full approval.

“People with triple-negative breast cancer have few treatment options, which is why today’s committee decision to recognize the importance of this Tecentriq combination is significant,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, said in a press release. “We are grateful to the FDA and ODAC for the open dialogue and look forward to continued collaboration to improve the lives of people with breast cancer.”

References

1. US FDA Advisory Committee votes in favour of maintaining accelerated approval of Roche’s Tecentriq for PD-L1-positive, metastatic triple-negative breast cancer. News release. Roche. April 28, 2021. Accessed April 28, 2021. https://bit.ly/2R9K6ao

2. FDA approves atezolizumab for PD-L1 positive unresectable locally advanced or metastatic triple-negative breast cancer. FDA. March 8, 2019. Accessed April 28, 2021. https://bit.ly/3nuhK74

3. Schmid P, Rugo HS, Adams S, et al; IMpassion130 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(1):44-59. doi: 10.1016/S1470-2045(19)30689-8.