FDA Informs on Lack of Efficacy and Safety of Atezolizumab/Paclitaxel in mTNBC

September 8, 2020
Nichole Tucker

Nichole Tucker, MA, is the Web Editor for Targeted Oncology. Tucker received her Bachelor of Arts in Mass Communications from Virginia State University and her Master of Arts in Media & International Conflict from University College Dublin.

The combination of atezolizumab and paclitaxel was not effective for the treatment of patients with treatment-naïve inoperable locally advanced or metastatic triple-negative breast cancer, according to an FDA alert.

The combination of atezolizumab (Tecentriq) and paclitaxel was not effective for the treatment of patients with treatment-naïve inoperable locally advanced or metastatic triple-negative breast cancer (mTNBC), according to an FDA alert released to healthcare professionals and clinical trial investigators in oncology.

Atezolizumab plus paclitaxel is being explored in the phase 2 IMpassion131 clinical trial(NCT03125902), which was designed to offer another option to frontline chemotherapy, the standard of care for the treatment of mTNBC. The study included 495 patients who were randomized 2:1 to receive atezolizumab plus paclitaxel compared with paclitaxel plus placebo. Patients enrolled were stratified by PD-L1 expression on tumor-infiltrating immune cells, prior taxane chemotherapy, and the presence and region of liver metastases. Patients were assessed for the primary end point of progression-free survival (PFS) measured by RECIST v1.1. The secondary end points included overall survival (OS), 12-month and 18-month OS rate, 12-month PFS rate, objective response rate (ORR), duration of response (DOR), and safety.

Statistical significance in terms of PFS was not met with the combination in the PD-L1-positive population of patients with mTNBC, announced Roche, the developer of atezolizumab. It was also revealed that the secondary OS showed a trend towards a negative result. The safety profile observed with atezolizumab plus paclitaxel was reportedly consistent with the known profile of either drug alone.

Based on these findings, however, the FDA warns against replacing paclitaxel protein-bound (Abraxane) with paclitaxel in clinical practice.

IMpassion131 shows failure of the atezolizumab plus chemotherapy in the frontline mTNBC setting only, as results from another study, Impassion130 (NCT02425891), showed a statistically significant improvement in PFS when atezolizumab was administered in combination with nab-paclitaxel to patients with mTNBC whose tumor express PD-L1. The combination of atezolizumab and nab-paclitaxel is also approved in more than 70 countries as treatment of this patient population.

Despite the unfavorable findings in IMpassion131, OS follow-up will continue until the final analysis. The FDA will later review the final results to make any necessary changes to the prescribing information. The FDA will also review data from all other clinical trials involving the combination of atezolizumab and paclitaxel and will recommend changes based on the information the regulatory body discovers.

IMpassion131 is a multicenter, randomized, double-blind, placebo-controlled trial that remains active, but is no longer recruiting patients. To be included, patients were required to have histologically documented disease, eligible for taxane monotherapy, naïve to chemotherapy, and targeted systemic therapy. Patients were also required to have an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks, measurable disease per RECISTS v1.1, adequate hematologic and end-organ function, and be free of comorbidities that may interfere with response to study treatment.


1. FDA alerts health care professionals and oncology clinical investigators about efficacy and potential safety concerns with atezolizumab in combination with paclitaxel for treatment of breast cancer. News release. FDA. September 8, 2020. Accessed September 8, 2020.

2. Miles D, Andre F, Gligrow J, et al. IMPASSION131: phase iii study comparing 1l atezolizumab with paclitaxel vs placebo with paclitaxel in treatment-naive patients with inoperable locally advanced or metastatic triple negative breast cancer (mTNBC)resented at ESMO Virtual Congress 2017. Abstract 3851

3. Roche provides update on Phase III study of Tecentriq in combination with paclitaxel for people with metastatic triple-negative breast cancer. News release. Roche. August 6, 2020. Accessed September 8, 2020.