Phase II First Line Atezolizumab, PacliTaxel,and Bevacizumab in mTNBC
Research type
Research Study
Full title
PHASE II CLINICAL TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF FIRST LINE ATEZOLIZUMAB IN COMBINATION WITH PACLITAXEL AND BEVACIZUMAB (AVASTIN®) IN PATIENTS WITH ADVANCED OR METASTATIC TRIPLE-NEGATIVE BREAST CANCER
IRAS ID
287270
Contact name
Melissa Phillips
Contact email
Sponsor organisation
Medica Scientia Innovation Research (MedSIR)
Eudract number
2019-001503-20
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Research Summary -
Patients with mTNBC still have a poor outcome despite advances in the fields of molecular biology and the introduction of new therapies. Several agents are under investigation in the clinical and pre-clinical setting with different targets and biomarkers designed to augment treatment.The hypothesis of this study is that the addition of atezolizumab to a bevacizumab-based chemotherapy could potentially surpass the benefit of the current standard (combination of atezolizumab and nab-paclitaxel) in mTNBC patients.
The goal of this study is to explore the potential synergism between bevacizumab (Avastin®) and atezolizumab with standard chemotherapy for mTNBC. It is mandatory to evaluate the additive effect between bevacizumab (Avastin®) and atezolizumab in patients with mTNBC (irrespective of PD-L1 expression) considering the contribution of angiogenesis to an immunosuppressive tumor microenvironment.Lay Summary -
Triple-negative breast cancer (TNBC) is a type of breast cancer characterized by the fact that the cancer cells don’t have estrogen or progesterone receptors (Hormone Receptors) and do not have any or much of a protein called Human Epidermal Growth Factor Receptor-2. TNBC accounts for about 10 to 15% of all breast cancers. Patients with TNBC at advanced stage have poor survival and fewer treatment options available than other types of breast cancer. Atezolizumab, an antibody that blocks the programmed-cell death ligand-1 (PD-L1) protein, combined with the chemotherapy agent nab-paclitaxel, is approved in multiple countries as first-line treatment in TNBC patients that present with an overexpression of PD-L1 (PD-L1-positive patients) as it has demonstrated a clinical benefit in terms of progression-free survival (PFS), which means the length of time in which cancer does not get worse, and overall survival.
Bevacizumab is an anti-angiogenic drug (a treatment that stops tumors from growing their own blood vessels, slowing their growth) in combination with paclitaxel has also demonstrated a sustained improvement in PFS, and is approved in Europe as the first treatment for metastatic TNBC.
In the ATRACTIB phase II study we investigated how effective the combination of atezolizumab, bevacizumab, and paclitaxel is in patients with advanced TNBC, regardless of their level of the protein PD-L1.
A total of 100 adult patients with untreated advanced TNBC were included in the study and received intravenous atezolizumab, bevacizumab and paclitaxel until disease progression, intolerable toxicity, death, or patient withdrawal. PD-L1 expression was assessed at the beginning of the study using immunohistochemistry. Tumor assessments were performed every 8 weeks for the first 12 months and every 12 weeks thereafter.
At the time of the analysis (15th September 2023), with a median follow-up of 16.7 months (range 1.1 - 34.1), the median PFS was 11 months, which means that 50% of patients had still not progressed at 11 months after treatment initiation. A total of 63 patients (63%) had a response to the treatment (13 and 50 patients with complete and partial responses, respectively), with a median duration of response of 10 months. The clinical benefit of the combination therapy was observed in 79% of patients.
Regarding safety, the most common secondary effects that emerged during the treatment were peripheral neuropathy (68%), a condition in which nerves in the hands, feet and arms are damaged and therefore causes pain and weakness, and fatigue (62%). Secondary effects attributed to treatment of grade 3/4 (those who required hospitalization or urgent medical intervention) occurred in 47% of patients, mainly peripheral neuropathy (13%) and neutropenia (12%), which is a decrease in white blood cells. There were no drug-related deaths.
In summary, the combination of the anti-PD-L1 atezolizumab plus bevacizumab added to chemotherapy as first-line treatment demonstrated encouraging antitumor activity in patients with advanced TNBC. Interestingly, most of them had PD-L1-negative tumors (97.6%). The observed PFS is much higher compared with that previously reported with other immunotherapy agents. The safety profile was consistent with the one previously observed with this combination, without significant added toxicity. These results merit further research of immunotherapy plus bevacizumab combinations for PD-L1-negative aTNBC patients.REC name
London - Hampstead Research Ethics Committee
REC reference
21/LO/0527
Date of REC Opinion
28 Jul 2021
REC opinion
Further Information Favourable Opinion