Roche's Tecentriq Plus Abraxane Shows Significant Survival Benefit as First Immune Therapy for PD-L1-Positive Triple-Negative Breast Cancer

June 06, 2019 News /BioonBIOON/ -- Swiss pharmaceutical giant Roche recently announced at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago the evaluation of PD-L1TumorFirst-line Treatment of Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer with Immunotherapy Tecentriq (Atezolizumab) Combined with Chemotherapy (Abraxane [Albumin-bound Paclitaxel], nab-Paclitaxel)Breast CancerUpdated Overall Survival (OS) Data from the Phase III IMpassion130 Clinical Study in Adult Patients with (TNBC).

In March this year, based on the study data, the U.S. FDA granted accelerated approval to Tecentriq in combination with chemotherapy (Abraxane) forFDAAn approved assay confirmedTumorPatients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) expressing PD-L1. This indication is approved under accelerated approval based on progression-free survival (PFS) data, and further approval will be contingent upon the verification and characterization of clinical benefit in confirmatory clinical trials.TNBC is an aggressive disease with a high level of unmet medical need. This approval makes the Tecentriq + Abraxane combination the first cancer immunotherapy regimen for the treatment of PD-L1-positive metastatic TNBC.

IMpassion130 was a multicenter, randomized, double-blind study that enrolled 902 patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who had not previously received systemic therapy for metastatic disease. The study evaluated the efficacy and safety of Tecentriq in combination with Abraxane as first-line treatment, compared with placebo plus Abraxane. Patients were randomized in a 1:1 ratio to one of the two treatment arms. The co-primary endpoints were progression-free survival (PFS) and overall survival (OS), assessed by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). PFS and OS were evaluated in all randomized patients (i.e., the intent-to-treat [ITT] population) and in PD-L1-positive patients. Secondary endpoints included objective response rate (ORR), duration of response (DOR), and time to deterioration in global health status/health-related quality of life (GHS/HRQoL).

Previously reported data showed that, compared with the placebo plus Abraxane regimen, the Tecentriq plus Abraxane regimen significantly reduced the risk of disease progression or death by 40% in patients with PD-L1-positive tumors (median PFS: 7.4 months vs. 4.8 months; HR=0.60; 95% CI: 0.48–0.77; p<0.0001).

The data from the second interim analysis were presented at this year’s ASCO Annual Meeting, with results consistent with those reported in October 2018 in EuropeTumorconsistent with the first interim analysis presented at the European Society for Medical Oncology (ESMO) Congress. At the second interim analysis, compared with the placebo plus Abraxane regimen, the Tecentriq plus Abraxane regimen failed to achieve a statistically significant improvement in overall survival (OS) in the intent-to-treat (ITT) population of all randomized patients (median OS: 21.0 vs. 18.7 months; HR=0.86; 95% CI: 0.72-1.02; p=0.078).

However, inTumorAmong patients with positive PD-L1 expression in tumor-infiltrating immune cells, the Tecentriq + Abraxane regimen demonstrated a clinically meaningful 7-month improvement in overall survival (OS) (median OS: 25.0 vs. 18.0 months; HR=0.71; 95% CI: 0.54–0.93). Due to the hierarchical analysis plan, no formal statistical testing of OS data was performed for the PD-L1-positive population. At 2 years of treatment, more than half (51% [43–59%]) of PD-L1-positive patients with metastatic triple-negative breast cancer (TNBC) treated with Tecentriq + Abraxane remained alive, compared with 37% (29–45%) in the control group. The study will continue to follow patients until the next planned analysis.

Additional analysis of patient-reported outcomes indicated that the combination regimen was well tolerated compared with Abraxane monotherapy. Tecentriq plus Abraxane demonstrated increased clinical benefit, without adversely affecting patients’ health-related quality of life (HRQOL) and daily functioning, and without increasing the toxicity burden. Extended safety analyses showed that the safety profile of the Tecentriq plus Abraxane treatment group was consistent with the known safety characteristics reported in the original data, with no new safety signals observed.

Sandra Horning, Roche’s Chief Medical Officer and Head of Global Product Development, stated, “Roche continues to advance transformative work in breast cancer. We are pleased to announce the latest overall survival results from the IMpassion130 study at the ASCO Annual Meeting; this was the first positive immunotherapy trial conducted in PD-L1-positive metastatic triple-negative breast cancer (TNBC). The Tecentriq plus Abraxane combination is approvedFDA"The first immunotherapy regimen approved for PD-L1-positive metastatic TNBC marks a major milestone in the treatment of this disease."

Breast cancer is the most common type of cancer in women, with over 2 million new cases diagnosed globally each year. Triple-negative breast cancer (TNBC) accounts for approximately 15% of all breast cancers and is more prevalent in women under the age of 50 compared to other subtypes.

Triple-negative breast cancer (TNBC) specifically refers to breast cancer that is negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2). It progresses rapidly, carries a very poor prognosis, and has a 5-year survival rate of less than 15%. TNBC is unresponsive to both hormonal therapy and HER2-targeted therapies (such as Herceptin), resulting in very limited clinical treatment options, with chemotherapy being the mainstay. Metastatic TNBC is among the most aggressive and difficult-to-treat forms of breast cancer.(BioValley Bioon.com)

Original Source:Roche presents data from across its breast cancer portfolio at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting