The FDA has issued an alert that the phase 3 IMpassion131 trial failed to show the effectiveness of atezolizumab plus paclitaxel in treatment-naïve patients with inoperable locally advanced or metastatic triple-negative breast cancer.
The FDA has issued an alert to professionals, investigators, and patients that the phase 3 IMpassion131 trial (NCT03125902) failed to show the effectiveness of atezolizumab (Tecentriq) plus paclitaxel in treatment-naïve patients with inoperable locally advanced or metastatic triple-negative breast cancer.1
The PD-L1 inhibitor in combination with paclitaxel is not approved for use in breast cancer, according to the FDA. However, a different combination comprised of atezolizumab and nab-paclitaxel (Abraxane) is approved for the treatment of adult patients with metastatic TNBC whose tumors express PD-L1 per an FDA-approved test. Continued approval of the combination is dependent on proven benefit of the combination in additional clinical trials.
The FDA warns that practitioners should not substitute paclitaxel protein-bound with paclitaxel in clinical practice.
Results from the trial showed that the combination did not show a statistically significant improvement in progression-free survival (PFS) when used as a frontline treatment for patients with PD-L1–positive TNBC, thus failing to meet the primary end point of IMpassion131.2
Moreover, a negative trend was observed with regard to overall survival in both the PD-L1–positive population and the total population, which was the secondary end point of the trial. However, IMpassion131 was not powered for this end point and the data had been immature at the time of the analysis.
“FDA will review findings of IMpassion131 and will communicate new information regarding the results and any potential changes to prescribing information,” the regulatory agency wrote in their alert. “FDA is also evaluating the use of atezolizumab and paclitaxel in ongoing clinical trials for breast cancer and will recommend additional changes as appropriate.”
The regulatory agency notes that patients who are currently receiving the atezolizumab plus paclitaxel for other approved uses should continue to do so, as directed by their doctor. Healthcare professionals should report any adverse effects associated with the use of the combination to the regulatory agency’s MedWatch Adverse Event Reporting program.
In the multicenter, randomized, double-blind phase 3 trial, investigators evaluated the safety and efficacy of atezolizumab in combination with paclitaxel compared with placebo plus paclitaxel in treatment-naïve patients with inoperable, locally advanced or metastatic TNBC.3
In the trial, participants were randomized 2:1 to receive intravenous (IV) atezolizumab at a dose of 840 mg on days 1 and 15 of every 28-day cycle in combination with 90 mg/m2 of paclitaxel on days 1, 8, and 15 of every 28-day cycle, or placebo matching the schedule of atezolizumab plus paclitaxel given in the investigational arm. Patients were treated until either disease progression, unacceptable toxicity, or the end of the study period, whichever occurred first.
The primary end point of the trial was PFS in the PD-L1–positive patient population and in the intent-to-treat (ITT) population. Key secondary end points include OS in the PD-L1–positive population and in the ITT population, and percentage of patients alive at 12 and 18 months. Other end points included 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 v1.1 in the PD-L1–positive and ITT populations.
In March 2019, the FDA approved the combination of first-line atezolizumab plus nab-paclitaxel for patients with unresectable locally advanced or metastatic PD-L1–positive TNBC based on data from the phase 3 IMpassion130 trial. Results from the trial showed that the addition of the PD-L1 inhibitor resulted in a 40% reduction in the risk of progression or death versus nab-paclitaxel alone in this patient population.3
The approval marked the first immunotherapy regimen to receive regulatory approval in breast cancer.