Phase 3 IMpassion131 Study Fails to Meet Primary End Point of PFS in Metastatic TNBC

The phase 3 IMpassion131 study, evaluating atezolizumab (Tecentriq) in combination with paclitaxel compared to placebo plus paclitaxel, did not its primary end point of progression-free survival (PFS) for the first-line treatment of patients with metastatic triple-negative breast cancer (TNBC) in the PD-L1-positive population, according to Roche, the agent’s developer.

In addition, the data for the secondary end point of overall survival (OS) demonstrated a negative trend; however, the study was not powered for the secondary end point of OS and data were immature at time of analysis. OS follow-up is therefore planned to continue until final analysis.

Importantly though, the safety of the atezolizumab combination appeared to be consistent with the known safety profile of the individual agents, and no new safety signals were discovered.

“While we are disappointed by the results from the IMpassion131 study, we are grateful for all the patients, families and physicians who were involved in the study," Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, said in a press release. "Today’s results underscore the need to better understand the cancer and immune system interactions, including the chemotherapy backbone and associated regimens. We remain committed to finding optimal treatments for all people living with this aggressive disease.”

The phase 3, multicenter, randomized, double-blind study is assessing the efficacy and safety of atezolizumab in combination with paclitaxel compared to placebo plus paclitaxel in individuals with previously untreated, inoperable, locally advanced or metastatic TNBC. Overall, the study enrolled 651 patients who randomized 2:1 to receive the atezolizumab combination or placebo plus paclitaxel.

The primary end point is PFS per investigator assessment (RECIST 1.1) in the PD-L1-positive population, followed by intention-to-treat (ITT) populations. Key secondary end points include OS, objective response rate, and duration of response in the PD-L1-positive and ITT populations.

Roche indicated that full results from the study are being discussed with global health authorities and will be presented at a future medical meeting. Moreover, the company suggested that the findings will also be used to inform existing and future studies in TNBC with atezolizumab in combination with paclitaxel.

Notably, in the previous IMpassion130 study, atezolizumab in combination with nab-paclitaxel (Abraxane) demonstrated a statistically significant benefit PFS and, while not formally tested, showed clinically meaningful improvements in OS for individuals with metastatic TNBC whose tumors express PD-L1 (≥1%). The combination is now approved in over 70 countries for the treatment of adults with unresectable locally advanced or metastatic TNBC whose tumors express PD-L1 (≥1%).

Reference:

Roche provides update on Phase III study of Tecentriq in combination with paclitaxel for people with metastatic triple-negative breast cancer [news release]. Basel. Published August 6, 2020. roche.com/media/releases/med-cor-2020-08-06.htm. Accessed August 7, 2020.