Tecentriq in Combination with Paclitaxel Meets Primary Endpoint of PFS but Shows Negative Trend in OS in Phase III IMpassion131 Trial for PD-L1+ Metastatic Triple-Negative Breast Cancer

Compiled by S. Li

On August 6 (local time), Roche announced data from the Phase III IMpassion131 clinical trial evaluating Tecentriq, a PD-L1 inhibitor, in combination with paclitaxel (chemotherapy) as first-line treatment for patients with PD-L1-positive metastatic triple-negative breast cancer (TNBC). The results showed that the study met its primary endpoint, with a statistically significant improvement in progression-free survival (PFS) in the Tecentriq plus paclitaxel group compared to the paclitaxel plus placebo group. However, regrettably, the secondary endpoint of overall survival (OS) demonstrated a negative trend.

IMpassion131 is a multicenter, randomized, double-blind Phase 3 study evaluating the efficacy and safety of Tecentriq in combination with paclitaxel in patients with previously untreated, unresectable locally advanced or metastatic triple-negative breast cancer (TNBC). A total of 651 patients were enrolled and randomized in a 2:1 ratio to receive either Tecentriq or placebo in combination with paclitaxel. The primary endpoint was progression-free survival (PFS) in the PD-L1-positive intention-to-treat (ITT) population, as assessed by investigators. Secondary endpoints included overall survival (OS), objective response rate, and duration of response.

It is reported that at the time of this analysis, the data were not yet mature, and the current data did not adequately support the secondary endpoint of overall survival (OS). The investigators plan to continue following up on OS until the final analysis. The safety profile of the Tecentriq combination regimen was consistent with the known safety profile of monotherapy, with no new safety signals identified. The complete results of the IMpassion131 study will be presented at future medical conferences.

In the previous IMpassion130 study, Tecentriq in combination with Abraxane (paclitaxel protein-bound particles for injectable suspension; active ingredient: nab-paclitaxel) demonstrated a statistically significant improvement in progression-free survival (PFS). Although not formally tested, this regimen showed a clinically meaningful improvement in overall survival (OS) among patients with metastatic triple-negative breast cancer (TNBC) whose tumors expressed PD-L1 in ≥1% of cells. Tecentriq combined with nab-paclitaxel is currently approved in more than 70 countries/regions for the treatment of adult patients with PD-L1-positive (≥1%) unresectable locally advanced or metastatic TNBC.

Breast cancer is the most common cancer among women, with over 2 million new cases diagnosed worldwide each year. Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the absence of estrogen receptors, progesterone receptors, and HER2 amplification. Consequently, targeted therapies directed at these receptors are generally ineffective in patients with this subtype. Approximately 15% of breast cancer cases are TNBC. Compared with other forms of breast cancer, TNBC is more prevalent in women under the age of 50. Metastatic TNBC progresses rapidly and is associated with shorter overall survival (OS).

Tecentriq is a monoclonal antibody that binds to PD-L1 and activates T cells by inhibiting PD-L1. It is a cancer immunotherapy with the potential to be used in combination with other immunotherapies, targeted drugs, and chemotherapy. Roche’s development program for Tecentriq is extensive, including multiple ongoing or planned Phase 3 clinical trials in urogenital cancers, skin cancer, breast cancer, gastrointestinal cancers, gynecological cancers, and head and neck cancers. These trials will evaluate the efficacy of Tecentriq as monotherapy or in combination with other agents. Tecentriq has been approved in the United States, the European Union, and many other countries/regions as monotherapy or in combination with other treatments for various forms of non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), certain types of metastatic urothelial carcinoma, and PD-L1-positive metastatic triple-negative breast cancer.

In China, Tecentriq has been approved in combination with chemotherapy for the treatment of small cell lung cancer, received priority review status for first-line treatment of advanced hepatocellular carcinoma, and initiated compassionate use clinical trials for triple-negative breast cancer.

Reference source: Roche provides update on Phase III study of Tecentriq in combination with paclitaxel for people with metastatic triple-negative breast cancer