Roche has made the voluntary decision to withdraw the indication for the use of atezolizumab plus chemotherapy in the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1.
Roche has made the voluntary decision to withdraw the indication for the use of atezolizumab (Tecentriq) plus chemotherapy in the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1.1
In March 2019, the FDA granted an accelerated approval to atezolizumab based on earlier data from the phase 3 IMpassion130 trial (NCT02425891), which showed that the addition of the PD-L1 inhibitor to chemotherapy resulted in a median progression-free survival (PFS) of 7.4 months (95% CI, 6.6-9.2) vs 4.8 months (95% CI, 3.8-5.5) with chemotherapy alone (HR, 0.60; 95% CI, 0.48-0.77; P < .0001) in patients whose tumors expressed PD-L1.2 At the time, overall survival (OS) data were immature.
Continued approval for this indication was dependent on data from the phase 3 IMpassion131 trial (NCT3125902), in which the PD-L1 inhibitor plus paclitaxel did not demonstrate a statistically significant improvement in PFS over paclitaxel alone when used as a frontline treatment in patients with PD-L1–positive TNBC, missing the study’s primary end point.3
Findings from both of the trials were discussed by the FDA’s Oncologic Drugs Advisory Committee, who in April 2021, still voted 7 to 2 in favor of maintaining the indication of atezolizumab plus nab-paclitaxel in patients with metastatic TNBC that is PD-L1 positive.4
Since this meeting, Roche has worked with the FDA to determine a potential alternative post-marketing requirement for the indication. However, in light of recent changes to the treatment paradigm, the regulatory agency no longer considers the regimen appropriate to maintain accelerated approval. As such, Roche has decided to voluntarily withdraw the indication.
“TNBC remains the most challenging type of breast cancer to treat, which makes the decision to withdraw so difficult to us, as patients have had this medicine as an important option for more than 2 years,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, stated in a press release. “We appreciate the opportunity to have been able to help people with metastatic TNBC in the United States with [atezolizumab] 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 [atezolizumab] in metastatic TNBC.”
The multicenter, randomized, double-blind IMpassion131 trial enrolled treatment-naïve patients with inoperable, locally advanced or metastatic TNBC.5 These patients were randomized 2:1 to receive atezolizumab at 840 mg on days 1 and 15 of every 28-day cycle plus paclitaxel at 90 mg/m2 on days 1, 8, and 15 of every cycle, or matching placebo plus paclitaxel. Treatment was administered until disease progression, unacceptable toxicity, or the end of the study period, whichever occurred first.
The primary end point of the trial is PFS in the PD-L1–positive population and in the intent-to-treat population. Secondary end points comprised OS in both populations, the percentage of patients alive at 12 months and 18 months, time to deterioration, percentage of patients alive without a progression event at month 12 assessed via RECIST v1.1 criteria, and percentage of patients with objective response per RECIST in both populations, among others.
Full findings from the trial will be shared at an upcoming medical meeting.