ODAC Votes to Continue Approval of Atezolizumab/Nab-Paclitaxel for Advanced or Metastatic TNBC

The FDA's Oncologic Drugs Advisory Committee voted 7 to 2 in favor of the continued approval of atezolizumab in combination with nab-paclitaxel for the treatment of patients with advanced or metastatic triple-negative breast cancer whose tumors are positive for PD-L1 expression.

The Oncologic Drugs Advisory Committee (ODAC) voted 7 to 2 in favor of the continued approval of atezolizumab (Tecentriq) in combination with nab-paclitaxel (Abraxane) for the treatment of patients with advanced or metastatic triple-negative breast cancer (TNBC) whose tumors are positive for PD-L1 expression.1

During an interview with Targeted Oncology, ODAC chairperson and professor of Medicine at the University of Chicago, Phillip C. Hoffman, MD stated, "I think many of the members who voted in favor of retaining the accelerated approval status were not persuaded that the negative confirmatory trial was clearly comparable. The company’s presentation laid out several potential factors that might have impacted the confirmatory study’s results besides the conclusion that atezolizumab is not effective in this setting."

Accelerated approval was granted to atezolizumab plus nab-paclitaxel for this indication in March 2019, after the combination demonstrated improvement in progression-free-survival (PFS) in patients with metastatic TNBC who were both in the general population of the phase 3 IMpassion130 clinical trial (NCT02425891) and in the subgroup of patients with PD-L1–positive tumors. The median PFS was 7.2 months with atezolizumab plus nab-paclitaxel compared with 5.5 months in the placebo plus nab-paclitaxel arm (HR, 0.80; 95% CI, 0.69-0.92; P = .002).

After a review of the data during the ODAC meeting, Roberto Montenergo MD, PhD, of the University of Washington Medicine argued that the OS results should not be discounted.

"Based on a principle of maximizing therapeutic options in aggressive terminal illness, most patients with stage IV TNBC live less than 2 years. It’s hard to discount the OS benefit observed in IMpassion130 based on the lack of statistical power. There seems a low likelihood of this being due to chance."

Continued approval of atezolizumab/nab-paclitaxel was contingent upon positive results from a confirmatory study, which was attempted with the phase 3 IMpassion131 clinical trial (NCT03125902). But, in August 2020, Roche announced that the trial did not show a statistically significant improvement in PFS in patients with metastatic TNBC who had PD-L1–positive disease.2 In addition, the trial showed a negative overall survival (OS) trend, although the study was not powered for it and the OS data were immature at the time the announcement was made.

IMpassion131 was a multicenter, randomized, double-blind study of 651 patients who were randomized 2:1 to receive either atezolizumab in combination with paclitaxel or placebo. In the study, atezolizumab was administered intravenously at 840 mg days 1 and 15 of a 28-day cycles. Paclitaxel was administered at 90 mg/m2 on days 1, 8, and 15, and patients in the placebo arm received the same dosing schedule.

During the ODAC public hearing, Diane Zuckerberg, PhD, president, National Center for Health Research, began with a presentation on the importance of having positive research behind FDA approved drugs. Zuckerberg highlighted the decrease in OS observed in patients with PD-L1–positive disease and was the only speaker during the hearing to oppose continued approval of atezolizumab for advanced or metastatic TNBC.

“We all want to give patients hope real hope not false hope. The FDA wants to help patients get timely access to treatments, but as a public health agency, [the] first priority needs to be evidence. Evidence should be based on the patients that most need the treatment, convoluted analyses, and backflips should not be necessary,” said Zuckerberg. “It doesn't help patients to continue to approve a treatment that is not proven to benefit them and is proven to harm. That's why we support continued research, but not continued approval.”

During the voting portion of the meeting, the question proposed to the committee was whether atezolizumab should continue to be approved based on the biomarker of positive PD-L1 expression. The question was raised based on the fact that the prior improvement in PFS was minimal, the benefit was not shown in a confirmatory trial, there is a possible detriment of OS for this patient population, and the current trials that are ongoing do not investigate atezolizumab in combination with nab-paclitaxel and are in different settings of TNBC.

The ODAC attendees who voted yes were Jennifer Spotlia, JD; Roberto Montenergo MD, PhD; Phillip Hoffman, MD;Stanley Lipkowitz, MD, PhD; Harold Burnstein, MD, PhD; Sandra Feinstone; and Christopher Leiur, MD. The attendees Matthew Elias, MD, and Susa Halabi, PhD, voted against continued approval of atezolizumab in advanced or metastatic TNBC.

Regarding the vote, Hoffman said: "There seemed to be consensus that it might be premature to withdraw the accelerated approval without more compelling and mature data—whether that might come from another trial already underway in the advanced (or possibly an earlier) setting, or whether another randomized trial is needed asking the same question."


April 27-29, 2021: Meeting of the Oncologic Drugs Advisory Committee Meeting Announcement. FDA website. Accessed April 27, 2021.

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 August 7, 2020. https://bit.ly/30AQwBI