FDA Advisory Committee Votes 7:2 to Retain Tecentriq's Accelerated Approval for PD-L1-Positive Triple-Negative Breast Cancer

Recently, the FDA held a three-day meeting on the accelerated approval of PD-1/L1 immuno-oncology drugs. On the first day, the expert panel discussed Tecentriq (atezolizumab) from Roche, one of the largest players in this field. Atezolizumab is a PD-L1 inhibitor, and Roche has been hoping to use it to make up for market share lost in biosimilar competition. Ultimately, the experts voted 7:2 to retain the drug’s approval pending further research.

In March 2019, based on the progression-free survival (PFS) results in PD-L1-positive patients from the IMpassion130 study evaluating atezolizumab in combination with Abraxane (nab-paclitaxel) for the treatment of PD-L1-positive metastatic triple-negative breast cancer (mTNBC) (7.4 months vs. 4.8 months; HR: 0.6; P < 0.0001), the U.S. Food and Drug Administration (FDA) granted accelerated approval to atezolizumab for the treatment of adult patients with PD-L1-positive, previously untreated, unresectable locally advanced or mTNBC. Full approval for this indication is contingent upon the results of the IMpassion131 study.

The IMpassion131 study was a confirmatory trial for the mTNBC indication. This study evaluated the efficacy of atezolizumab plus paclitaxel versus placebo plus paclitaxel as first-line treatment in patients with previously untreated, unresectable, locally advanced or metastatic TNBC. The primary endpoints were median progression-free survival (mPFS) in the PD-L1-positive population and the intent-to-treat (ITT) population. However, the study results showed that Tecentriq combined with paclitaxel did not prolong survival in TNBC patients who were PD-L1 positive or in the ITT population. The mPFS for PD-L1-positive patients was 6.0 months and 5.7 months, respectively, while the mPFS for the ITT population was 5.7 months and 5.6 months, respectively.

Several factors may explain the discrepancy in results between “IMpassion130” and “IMpassion131.” These include changes in pre-treatment standards, differences in statistical design of the trials, and variations in median follow-up. Following technical issues that disrupted the meeting, experts voted 7 in favor and 2 against to continue approval for this indication, allowing investigators to collect more data on this combination therapy.

In the report, Roche expressed confidence in observing the benefits of atezolizumab combined with Abraxane for the treatment of patients with triple-negative breast cancer (TNBC) in upcoming confirmatory trials. Meanwhile, Dr. Stephen Chui, Medical Director of the Oncology Product Development Group at Genentech, a member of the Roche Group, stated that given the current lack of effective therapies for TNBC, the company agrees to keep this combination therapy on the market.

Chui stated that Roche had discussed with the FDA last December several approaches to obtaining confirmatory clinical trial data, including repeating the initial pivotal clinical trial. He added that a more practical solution would be to await data from three ongoing studies in relevant patient populations, including a clinical trial evaluating treatment for patients with early-stage triple-negative breast cancer (TNBC).

Tomorrow, another indication for atezolizumab, which received accelerated approval from the FDA, will also face discussion by the expert panel. This indication is for the first-line treatment of locally advanced or metastatic urothelial carcinoma (mUC) in patients who are not eligible for platinum-based chemotherapy.